Genetic Counseling Boards Practice-Tay

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Peutz-Jeghers syndrome

-Hamartomatous (benign) polyps throughout GI tract and mucocutaneous hyperpigmentation (freckle-like spots) on lips, oral mucosa, and genital skin; -autosomal dominant disorder

Deletion 9q34 (Kleefstra syndrome)

-LD -hypotonia, obesity, sleep disturbance, behavioral, epilepsy, speech delays -The facial features typically described include arched eyebrows, small head circumference, midface hypoplasia, prominent jaw and a pouting lower lip

Hunter's Disease

-Lysosomal storage disease, type Mucopolysaccharidoses. Deficiency of Iuronate Sulfatase, accumulation of Heparan and Dermatan sulfate. -Findings: Mild hurler's + agressive behaviour and NO corneal clouding. -X-linked (you cant hunt with clouded cornias)

A 6-year-old boy is referred to clinic due to several cutaneous findings associated with Neurofibromatosis type 1 (NF1), Constitutional Mismatch Repair Deficiency (CMMRD), and Fanconi Anemia (FA). Subsequent genetic testing reveals a homozygous pathogenic variant in the FANCC gene. Following this diagnosis, the patient should receive multidisciplinary management, including screening for what type of tumor?

Oral squamous cell carcinoma

Use of vocabulary appropriate to a young client's level of cognitive development is important. true or false?

True

When a person with a metabolic disorder has a crisis triggered by fasting, not enough energy is coming in from the outside. The body then has to break down carbohydrates and fats. This is often seen with glycogen storage diseases and gluconeogenesis defects. True or false?

True

TRUE or FALSE: Removal of the ovaries, fallopian tubes and uterus are critical in reducing cancer risk in women with a BRCA1 or BRCA2 mutation.

false

The contemplation stage is when clients know they have a problem,but are highly resistant to taking ownership of the problem. true or false?

false

The purpose of the interview can still progress even if the client has difficulty sharing information. true or false?

false

True or False: Presymptomatic diagnosis for Huntington's disease requires DNA analysis of at least one affected relative

false

True or False: Robertsonian translocations usually involve metacentric chromosomes.

false

True or False? A karyotype can be used to detect genetic disorders such as Down syndrome, sickle-cell anemia or Tay-Sachs disease in an unborn child.

false

True or False? Klinefelter syndrome could result from non-disjunction occurring during meiosis II in a male.

false

True or False? Nondisjunction is an error in meiosis which can affect only three different human chromosomes, plus the sex chromosomes.

false

True or False? Sex-linked recessive traits can be seen only in men, because they result from genes located on the X chromosome.

false

After a genetic mutation, what feature leads to the next highest risk for developing breast cancer?

family history

disorders of carnitine metabolism affect what?

fatty acids

tumor type: NF1

malignant peripheral nerve sheath tumor

Connective tissue disorder examples

marfan, beal, loeys-dietz, familiam thoracic aortic aneurysm, ehler-danlos, pseudoxanthoma elasticum (PXE)

Interviewers who establish a conversational distance of slightly over one arm's length distance are considered most comfortable for European North Americans. true or false?

true

MYH-associated polyposis is the only autosomal recessive polyposis syndrome true or false

true

Neuroscience has learned that "neurons that fire together wire together." true or false?

true

Pre-contemplation stage is when clients are unaware they are encountering a problem in life. True or false?

true

Programmed learning is a way of combining microskills into larger units for easy learning of listening and action skills. true or false?

true

Reflecting feeling requires more attending skill than reflecting content. true or false?

true

Research indicates that self-disclosure can tip the balance of influence in the relationship to the interviewer. true or false

true

Restricting the amount of information given or overwhelming the interviewer with too much information are both ways of showing resistance. true or false?

true

Self-disclosure should focus clearly and accurately on a particular client issue true or false?

true

Some interviewers believe that self-disclosure can take the focus away from the client's issues and change the flow of the session. true or false?

true

T/F The karyotype of a spontaneous abortion is more likely to be abnormal than that of a stillborn infant.

true

The most common cause of death for people with metastatic CRC is liver failure true or false?

true

True or False? Genetic disorders such as Down syndrome, Turner's syndrome or Tay-Sachs disease could be detected in unborn children by amniocentesis.

true

True or False? The Y chromosome is responsible for male development in mammals, so even aneuploid mammals with a Y chromosome (XXY, XXXY, XXXXY, etc.) would be male.

true

While most colon cancers had been treated with 5-FU in the past, treating MSI-high tumors with 5-FU is now known to be less effective. true of false?

true

Retinoblastoma

tumor arising from a developing retinal cell (a congenital, malignant tumor)

autosomal recessive

two copies of an abnormal gene must be present in order for the disease or trait to develop

Werding Hoffman syndrome

-Type I SMA -breathing issues, hypotonia, lack of tendons reflex, swolling and feeding problems. -AR

tumor type: Li Fraumeni syndrome

choroid plexus carcinoma

Individuals with hereditary retinoblastoma have increased risks for all of the following cancers EXCEPT: A. Breast B. Osteosarcoma C. Melanoma D. Brain

Tyrer-Cuzick Model

This model and its associated IBIS Breast Cancer Risk Evaluation Tool incorporate both genetic and nongenetic factors into a computer program that gives a personalized risk estimate.

two hit hypothesis

Tumor suppressor genes typically require both copies to be inactivated before an effect is seen.

Lack of cooperation refers to client resistance and reluctance. true or false?

true

T/F It is possible to have the Down syndrome phenotype and have 46 chromosomes.

true

True or False? Nondisjunction of all chromosome pairs in meiosis could result in polyploidy, but polyploid individuals cannot survive.

true

Fetal valproate syndrome

neural tube defects (meningomyelocele, spina bifida, cardiac defects, facial clefts, hypospadius, limb defects, radial aplasia.

Birt-Hogg-Dube syndrome

Thin-walled oval-shaped lung cysts (looks like LAM) Bilateral renal oncocytomas, chromophobe RCC FLCN -AD Associated with multiple non-cancerous (benign) skin tumors, lung cysts, and an increased risk of kidney lesions increased chance of developing cysts in the lungs resulting in pneumothoraxelevated risk of developing cancerous or noncancerous kidney tumors

CDKN2A, CDK4

What gene mutations are associated with dysplastic nevi and melanoma Familial melanoma, squamous cell carcinomas (mouth, nose, and throat), breast cancer, and pancreatic cancer

NF2

AD Tumor Suppressor (2 hit) NeuroFibromatosis type 2 Merlin (schwannomin) protein

What is the most significant risk factor for cancer?

Age

MYH-associated polyposis

(AR) MYH Y165C and G382D; DNA repair gene; similar to attenuated FAP

Conflict of interest issues have nothing to do with multiple relation and boundary issues. true or false?

false

Frame of reference refers to how interviewers' perspective shapes their worldview. true or false?

false

Muir-Torre syndrome

-Rare autosomal disorder consisting of visceral malignancies, sebaceous adenomas and carcinomas, and keratoacanthomas -AD

Narrative therapy is beneficial because its focuses on the here and now true or false?

false

Birt-Hogg-Dube syndrome

-Thin-walled oval-shaped lung cysts (looks like LAM) Bilateral renal oncocytomas, chromophobe RCC -AD mutation in FLCN

Which of the following is an example of a tumor suppressor gene? A. CDK4 B. BRCA2 C. KIT D. CFTR

ATM

Moderate risk breast Pancreatic also slightly increased

T/F The most common Down syndrome karyotype involves a Robertsonian translocation between chromosomes 14 and 21

false

WAGR syndrome

-Wilms tumor. Aniridia. -Genitourinary abnormalities. -Mental retardation. -Del (11p) -1 in 500,000 to one million individuals

TRUE or FALSE: Low grade serous ovarian cancer is associated with BRCA1 and BRCA2 mutations.

false

Lesch-Nyhan syndrome

-X-linked disorder characterized by intellectual disability, signs of cerebral palsy, and self-injurious behavior -HPRT gene

What skin lesion is common in FAP

Epidermoid cysts

Kabuki syndrome

• Rare, multisystem disorder characterized by multiple abnormalities including distinctive facial features, growth delays, varying degrees of intellectual disability, skeletal abnormalities, and short Hirshbrung disease • Kabuki syndrome is most often caused by a mutation in the KMT2D gene, and inherited in an autosomal dominant manner. Some cases are due to a mutation in the KDM6A gene and are inherited in an X-linked dominant manner. Treatment is focused on the specific signs and symptoms in each affected person. • Rare congenital disorder, meaning that a child is born with the condition. • Children usually have distinctive facial features, mild to moderate mental impairment and growth problems. • Can also affect many other body systems, including the heart, intestines, kidneys and skeleton. • Occurs in about one out of every 32,000 births. It affects males and females equally.

Aarskog syndrome

- hypertelorism, - shawl scrotum, - brachydactyly, - short stature, - cryptorchidism, - cervical vertebral abnormalities, - ID (30%), - milder manifestations in females CLINICAL TESTS: - x-ray MOLECULAR TESTS: - FGD1 sequencing (7-20%) - Rho/Rac Guanine nucleotide exchange factor

Burgada Syndrome

-AD -20-30% SCN5A -more common in men -dizziness; syncope, labored breathing, irregular heartbeat and palpitation

van der syndrome

-cleft lip/palate, AD

Diamond-Blackfan anemia

AD RPS19 Blood disorder impacting bone marrows ability to create red blood cells increased risk of leukemia and sarcoma (specially osetosarcoma)

Examples of Peripheral neuropathies

Charcot Marie Tooth disease Spinal Muscular Atrophy Werdnig Hoffman disease Motor neuron disease

Beckwith-Wiedemann Syndrome

Overgrowth disorder1 in 13,700 (increased in IVF 3-4 fold)85% sporadic, 15% familiald/t dysregulation of imprinted expression in Ch11p15.5 region (paternal gene imprinted). Affects critical genes in domain 1 (IGF-2 (overexpression of foetal growth factors) and H19 (tumour suppressor gene))5 common feats:Macroglossia Macrosomia Midline abdominal wall defects Ear creases/pits Neonatal hypoglycaemia Other possible feats incl. port wine stain, prominent occiput, midface hypoplasia, hemihypertrophy, cardiomyopathy, nephromegaly, hearing loss INCREASED RISK of childhood cancer (600-fold) esp embryonal tumours (Wilm's + hepatoblastoma), and less likely andrenal coritcal carcinoma, neuroblastoma and rhabdomyosarcoma Screened for Ca with 3 monthly abdo U/S until 8 yo and 6 weekly AFP for hepatoblastoma

Smith-Magenis Syndrome

RAI1, 17p11.2 deletion 90%, AD -Congenital heart defects -Scoliosis -Hearing impairment -Self harming -Self hugging -Moderate to severe learning disabilities -Sleep disturbances -1 in 25,000 individuals worldwide

Multiple endocrine neoplasia, type 2

RET Medullary thyroid cancer, parathyroid tumors, pheochromocytoma

Polyploidy

condition in which an organism has extra sets of chromosomes

tumor type; Von Hippel-Lindau syndrome

endolymphatic sac tumor

tumor type: Beckwith-Wiedemann syndrome

hepatoblastoma

When sucrose is broken down, one of the byproducts is fructose. Infants with hereditary fructose intolerance classically present when they begin to eat fruit, around 4 - 5 months of age. Why must clinicians who treat infants be aware of fructose intolerance? Check all that apply. -there is sucrose in IV fluids, which could be harmful to an affected baby -there is sucrose in formulas, and it could be harmful for an affected baby -there is a risk for future dental cavities -there is sucrose in some medications, which could be harmful to an affected baby there is a risk of sucrose allergy, which could be dangerous

- there is sucrose in IV fluids, which could be harmful to an affected baby - there is sucrose in formulas, and it could be harmful for an affected baby - there is sucrose in some medications, which could be harmful to an affected baby

Potter syndrome (aka Potter sequence)

-1/4000 live births. neonatal lethal. Primary defect: Renal agenesis. -severe oligohydramnios, polycystic kidney, and obstructive uropathy during middle gestational weeks. -Typical Potter facies, club feet, contractors due to deformation (from oligo) and lung hypoplasia.

von Hippel-Lindau disease

-40% RCC. 75% simple renal cysts. Hemangioblastomas CNS. Retinal angiomas. Pancreatic cysts. Pancreatic neoplasms. 50-80% Pheochromocytomas (multiple, bilateral, extraadrenal). -AD

Germline mosaicism

-A proportion of gametes have a mutant allele (as opposed to a sporadic mutation where 1 gamete had a mutation). -Therefore, can have normal parents pass on an AD disorder

Hurler's disease

-A type of lysosomal storage disease in which a hydrolase responsible for the breakdown of certain glycosaminoglycans is mutated or deleted -most severe, death by age 10y, progressive ID -AR

myotonic dystrophy

-AD, CTG repeat in DMPK gene, maternal anticipation, 3' UTR of gene5-30: normal38-54: permutations (unaffected, risk of passing on expanded allele)50-150: mildly affected (cataracts, myotonia)100-1000: myotonia, muscle weakness, diabetes, male pattern baldness, cataracts, hypogonadism, cardiac conduction defects>1000: congenital form. -Severe neonatal hypotonia, ID, respiratory problems

Cowden syndrome

-AD. -Multiple hamartomatous syndrome, common in skin and mucous membranes along with GI tract.

Fabray's Disease

-Children inherit a mutation (change) in the galactosidase alpha (GLA) gene on the X chromosome from a parent. Numbness, tingling, burning or pain in the hands or feet. Extreme pain during physical activity. Heat or cold intolerance. Abnormal opacity of the eye (cornea), which does not change someone's vision. Dizziness. Flu-like symptoms, including fatigue, fever and body aches. Gastrointestinal problems, such as diarrhea, constipation and abdominal pain. Hearing loss or ringing in ears (tinnitus). High levels of protein in urine (proteinuria). Raised red or purplish skin lesions (angiokeratoma) on your chest, back and in the genital area. Sweating less (hypohidrosis) or not at all (anhidrosis). Swelling (edema) in the legs, ankles or feet.

DiGeorge Syndrome

-Chromosome 22q11.2 -Cardiac anomalies -Abnormal facies -Thymic hypoplasia -Cleft palate

Robin sequence

-Mandibular growth restriction leads to posterior placement of the tongue, which obstructs the closure of the palate. -May be due to primary micrognathia, hypotonia, generalized growth retardation or an obstetric issue (oligohydramnios) that causes a deformation. -multifactorial inheritance(AD most severe)

Scheie syndrome

-Milder form of Hurler syndrome with normal intelligence and relatively normal life span. -This syndrome is also inherited in an autosomal recessive manner. Clinical features include: -Aortic regurgitation -Stiff joints -Corneal clouding

Leigh Syndrome

-Mitochondrial disease -early onset neurodegeneration w/hypotonia, DD, optic atrophy and respiratory abnormalitiesInheritance: mtDNA (ATPase) or nuclear DNA genes

Fragile X Syndrome

-XL, CGG repeat in 5' UTR of FMR1 gene, maternal anticipation1/4000 male births, 2nd most common -heritable form of ID (Down syn is #1). Always considered in differential diagnosis of a child (male or female)<45: ---normal45-54: intermediate55-200: premutation (FXTAS: ataxia/tremor syndrome and POI)>200: fragile X syndrome (females have 50-60% penetrance)AGG interruptions may stabilize locus = less risk of expansion

Goltz Syndrome

-aka focal dermal hypoplasia -x-linked dominant mutation in PORCN -lethal in males -linear atrophy along Blaschko's lines w/ areas of fat herniation + underlying osteopathia striata (striations of long bones, looks like linear bony hyperdensity) -mucocutaneous papillomas & pits -alopecia -nail dystrophy -tooth abnormalities -colobomas

Ataxia Telangiectasia

-an AR disease due to defect in DNA repair enzymes. The DNA of these patients is hypersensitive to ionizing radiation. -Manifestations include cerebella ataxia (and atrophy, telangiectasias, repeated sinopulmonary infections, and an inreased incidence of malignancy. Defect in the ATM gene.

deletion 16p 11.2

-deletion syndrome is a disorder caused by a deletion of a small piece of chromosome 16. The deletion occurs near the middle of the chromosome -impaired communication and socialization skills, as well as delayed development of speech and language.

Deletion 1p36 syndrome

-hypotonia, microcephaly, growth delays, epilepsy, straight eye brows, deep set eyes, mid face -most affected individuals do not speak, or speak only a few words. -20% inherited

Nijmegen breakage syndrome

-mutation in NBS1 gene (impaired homologous recombination in ds break) -autosomal recessive -hypersensitivity to ioniziation radiation, microcephaly, growth retardation, immunodeficiency, predisposition to cancer

Pfeiffer's Syndrome

1 in 100,000AD inheritance from mutations in FGFR1 and FGFR2 genes FACE AND HANDS affected FACE- variable craniosynostosis (cf branchial arch syndromes) - other facial features consistent with Crouzon's HANDS- thumb/great toes broad and deviated away from other digits - brachydactyly - may have some syndactyly Other feats: - Most have normal IQ- 50% have hearing loss

Apert's Syndrome

1 in 100,000Branchial arch syndrome affecting FIRST branchial arch AD inheritance (most sporadic) with 2/3 secondary to C --> G mutation in the FGFR2 gene FACE AND HANDS affected Feats: FACE- craniosynostosis (esp bicoronal --> brachycephaly)- flat/concave face (midface growth failure)- shallow bony orbits --> exophthalmos - broad-spaced eyes - pseudomandibular prognathism (severe underbite)- low-set ears - high prominent forehead - high arched palate with dental crowdingHANDS (4 common feats) - short thumb with radial deviation - complex syndactyly of index, middle and ring fingers- symphalangism (stiff, ankylosed PIPs) - simple syndactyly of the 4th webspace* normal fusion of cranial sutures - Lamboid/Coronal/Sagittal 22 - 39 months- Metopic 3 - 9 months

Prader-Willi Syndrome

1 in 15,000 Example of genomic imprinting PATERNALLY INHERITED as maternal gene imprinted ("switched off"). Caused by deletion or inactivation on paternal Ch15q or d/t UPD (2 maternal imprinted copies) Clinical feats: - Hypotonia - FTT as infants then hyperphagia and obesity in childhood/adolescence - Mental retardation (mild to moderate) - Hypogonadotrophic Hypogonadism (small external genitalia) - Dysmorphism incl. almond eyes, narrow frontal diameter, small hands/feet, short stature. Diagnosis: Methylation analysis or FISH (for microdeletion) Management: testosterone/oestrogen regularly + diet control

Bardet Biedl Syndrome

1 in 150,000AR inheritance with variable expression Ciliopathic condition Feats:- Obesity- Retinitis pigmentosa (initially night blindness then progressive degeneration) - Postaxial polydactyly - Hypogonadism - Renal failure - Mental retardation (not essential)

Turner Syndrome

1 in 2,00045, XO (ie absence of second X chromosome in girls)Clincal feats: From birth- oedema of dorsum of hands/feet - loose skin folds at nape of neck - low birth weight - low body lengthChildhood - webbing of neck - low posterior hairline - small mandible - prominent ears - epicanthal folds - high -arched palate - broad chest with wide spaced nipples - cubitus valgus - hyperconvex finger nails - short stature - sexual maturation failure (adrenarche normal, but delayed pubarche, and have premature menopause (infertile by 2 yo)NORMAL INTELLIGENCEOther problems: - Congenital heart disease, esp bicuspid aortic valve, aortic dilatation, partial anomalous pulmonary venous drainage, CoA, AS, MV prolapse - Premature coronary artery disease - Renal malformations (risk of HTN and UTI's) - 30 - 50% have thyroid autoantibodies, therefore potential for autoimmune thyroid disease - increased risk of coeliac diseaseMx - growth hormone in early childhood for short stature and oestrogen replacement in adolescence

Angelman Syndrome

1 in 20,000 (boys = girls) Example of genomic imprinting MATERNALLY INHERITED as paternal gene imprinted ("switched off"). Caused most commonly by deletion or inactivation of UBE3A gene on Ch15 on maternal copy, or d/t UPD (2 paternal imprinted copies) Clinical feats (happy puppet): - Mental retardation (gross motor + speech delay with low IQ) - AbN behaviour with frequent hand clapping, tongue thrusting/mouthing, paroxysmal laughter - Ataxia (puppet-like) - Truncal hypotonia - Jerky arm movements - Dysmorphism (usually not until 5 yo) incl brachycephaly, pointed chin, deep-set blue eyes, large mouth with wide-spaced teeth, small hands/feet- Seizures (usually start in 2nd year of life and improve with age) Diagnosis: methylation analysis (detects 80% of cases but doesn't distinguish mechanism) or FISH (doesn't detect UPD) Pathognomonic EEG pattern (interictal) with very large amplitude 2-3 Hz rhythm predominantly in prefrontal leads

Usher Syndrome

1 in 23,000 AR inheritance with multiple different genes can be responsible Feats (DEAF and BLIND): - sensorineural deafness - gradual visual impairment (secondary to retinitis pigmentosa, therefore initially degeneration of rod cells (night blindness/periopheral vision loss) then cone cells/macula (central acuity loss)

Goldenhar Syndrome

1 in 3,500 - 1 in 26,000 AKA hemifacial microsomia Caused by AbN development of 1st/2nd branchial archesAD/AR inheritance, but many sporadic Clinical feats (OMENS):Orbits - micropthalmia, colobomas and retinal problemsMandible - hypoplasia of mandible/malar/maxilla (70% unilateral, esp R) side)Ears - external (small to absent with pre-auricular skin tags), narrow EAC, sensorineural hearing loss Nerve - Arnold Chiari malformation, agenesis of corpuls callosumSoft tissue - cleft lip/palateOther feats seen - heart defects, renal problems, lung hypoplasia, 15% with low IQManagement - symptomatic/cosmetic

Fragile X Syndrome

1 in 3,600 (less common in girls)Most common cause of inherited mental retardation Caused by CGG triplet repeat affecting FMR1 (Fragile x Mental Retardation 1) gene on ChX (FMR protein required for neural development) Boys show complete penetrance, whereas girls only 50% d/t other normal X chromosomeFeats: - intellectual impairment (IQ ave 40 in boys) - often with autistic type behaviours, ADHD and anxiety- large, protruding ears - long face - high arched palate - hyperextensible finger joints - double jointed thumbs - pes planus - post -pubescent macro -orchidism - hypotonia - higher risk of seizures Dx: - Direct PCR testing and Southern Blot analysis Number of repeats important Premutation = 50 - 200Fragile X syndrome = >200

Kallman Syndrome

1 in 4,000 XLR inheritance of variable mutations, incl some with mutation of KAL gene (important for neural migration Clinical feats (2 main): - Anosmia (abN development of Olfactory lobe) - Hypogonadotrophic hypogonadism (central d/t neurons secreting GnRH migrate from Olfactory placade to hypothalamus) - testes usually < 3 mL volume, infertile and failure to start/complete pubertyOther feats:- cleft palate- unilateral renal agenesis - cryptorchidism - synkinesis (miror moving of hands) - congenital deafnessIx: - decreased FSH/LH - delayed bone age

Treacher-Collins Syndrome

1 in 50,000AD inheritance with variable penetrance Craniofacial tissues fail to develop correctly as a direct result of neural crest cell dysfunction Key problem is abnormal 1st and 2nd branchial arch development Subtypes (3 and account for 90% of cases):I - mutation in TCOF1 gene on Ch5II - mutation in POLR1D gene on Ch13III - mutation of POLR1C gene on Ch6 (this is AR)Feats: - malar hypoplasia/absent cheekbones - cleft zygoma - antimongoloid eye slant - colobomas along lateral 1/3 of lower lid - absent lashes medial 2/3 of lower lid - convex face shape with retrusive chin/jaw - cleft lip/palate - choanal atresia - external ear abNs with profound sensorineural hearing loss

Waardenburg Syndrome

1 in 50,000AD inheritance5 major feats: 1. Sensorineural hearing loss 2. Hair hypopigmentation (white hair lock) 3. Dystopia canthorum (lateral displacement of inner canthi) 4. Heterochromia irides (or brilliant blue eyes)5. First degree relative with WS 5 minor feats: 1. Skin hypopigmentation 2. Synophrys 3. Broad nasal root 4. Hypoplasia alae nasi 5. Premature (<30yo) graying of hairSubtypes by gene affected: Type I - PAX3 Type II - MITF Type IV - PAX3 = have Hirschsprung's(type II and IV may be AR inherited)

Klinefelter Syndrome

1 in 500 - 1 in 1,000AKA XXY syndrome (47XXY) Occurs in males only, due to presence of Y chromosome Caused by prezygotic meiosis error from maternal or paternal side, although increase risk of error on maternal side with advanced age Rare variants 48XXYY/XXXY and 49XXXXY (the more X's, the more likely other heart/neuro probs, and the more Y's (ie the more male), the more likely to be serious behaviour and IQ probs) Clinical feats: - Tall stature (long limbs) - Hypergonadotrophic hypogonadism (100% are infertile) incl small/hard testes and penis, partial virilisation, and 40% have gynaecomastia - Low IQ - Behaviour problems incl ADHD/anxietyIncreased cancer risk, esp germ cell tumours of the mediastinum, lymphoma/leukaemia, and male breast cancer Diagnosis: Karyotype. Also find very high FSH/LH/Oestrodiol but very low testosterone Management: lifelong testosterone therapy

At what risk level is it appropriate for a woman to be offered chemoprevention in the form of tamoxifen or raloxifene to reduce her breast cancer risk?

1.7% 5 year risk as calculated by the Gail model

Albinism is a harmless autosomal recessive trait. If we assume that 2% of the general population are carriers of the albinism gene, how likely is it that the child of an individual with albinism will also be affected if the partner is healthy and unrelated? A. 1 in 100 B. 1 in 4 C. 1 in 200 D. 1 in 50 E. 1 in 25

1/100

If an X-linked dominant disorder affects 1/100 males in a population, what is the gene frequency for the disorder in the population?

1/100

If an X-linked recessive disorder in a particular population affects approximately 1/1,000,000 females (all homozygous), what is the expected frequency of affected males in the population?

1/1000

What is the probability of having an affected child with an autosomal recessive disease if one parent is affected and the other is a carrier? A. 1/2 B. 2/3 C. 1/4 D. Virtually zero E. 1/8

1/2

A Caucasian couple seeks genetic counseling because the wife's niece has cystic fibrosis. Assume the incidence of CF in the Caucasian population is 1/2,500. Before screening for mutations in the affected individual, what is the risk for this couple to have a child with CF? A. 1/100 B. 1/160 C. 1/200 D. 1/400 E. 1/800

1/400

The affected individuals have Duchenne muscular dystrophy (DMD). By pedigree analysis, what is the chance that the fetus will be clinically affected with DMD? -mothers two brothers have DMD -fathers maternal aunt's son has DMD A ½ B ¼ C. ⅛ D. 1/16 E. 1/48

1/8

Simon is a 2-year-old boy recently diagnosed with unilateral retinoblastoma and is referred to genetics for counseling. In taking the family history, it is learned that has a healthy 4-year-old sister and the family history is negative for retinoblastoma or any other cancer. His parents decide to pursue RB1 genetic testing to determine whether Simon harbors a heritable RB1 What is Simon's a priori risk to have a germline mutation?

15%

Hemophilias

2 forms of hemophilia, A and B, similar clinical features, both XLR Incidence 1 in 5000 males A rare disorder when the blood doesn't clot properly due to lack of sufficient blood clotting proteins Replacement therapy is the current practice Recombinant product has been developed to avoid patient producing antibodies to the clotting factors Major health concern is deep bleeding inside the body, damage organs, tissues, and joints, life threatening Mild - bleeding may only occur after surgery or trauma Severe - spontaneous bleeding, large/deep bruises, unusual bleeding after vaccinations, pain, swelling or tightness in joints, blood in the urine or stool, nosebleeds, unexplained irritability in infants, bleeding in the brain (can result from a simple bump on the head)

What percent of VHL is due to a de novo mutation?

20%

Approximately what percentage of RB1 mutations are de novo?

60%

What is the earliest age at which 90% of patients with NF1 meet 2 or more of the NIH diagnostic criteria for NF1?

What percent risk reduction is associated with a bilateral prophylactic mastectomy?

90%

A disorder causing muscle weakness and epilepsy afflicts several members: All mothers are effected and all children A. Mitochondrial Inheritance B. recessive C. X-linked dominant D. Autosomal dominant E. X-linked recessive

A genetic counselor meets with the parents of a 15-year-old girl who was recently diagnosed with Turner syndrome. The parents do not want their daughter to be informed about her diagnosis because they feel that it will upset her and they prefer to wait and tell her themselves when they think that she is ready. Which of the following is the BEST approach by the counselor? A. Discuss strategies for talking about this diagnosis with girls her age B. Encourage the parents to join the local Turner syndrome support group C. Honor the parents' request because the patient is a minor D. Insist they share the diagnosis with their daughter as soon as possible

A man has been diagnosed with a mitochondrial disorder characterized by myopathy, hearing loss, ataxia, and depression. His sister, mother, maternal aunt, and maternal grandmother are similarly affected. What is the risk to his daughter and son, respectively? A. 0%, 0% B 50%, 0% C 0%, 50% D. 50%, 50%

A man with tuberous sclerosis is having a child with a woman diagnosed with Crouzon syndrome. What is the chance that their child will have both conditions? A. 25% B. 50% C. 75% D> 100%

For which genes would it be appropriate to perform genetic testing in childhood? A. APC, NF1, VHL, RET B. PMS2, NF1, APC, BRCA1/2 C. BRCA1/2, NF1, APC, RET D. VHL, RET, BRCA1/2, PMS2

Multiculturalism encompasses: A. An understanding of the values and attitudes of others B. Sharing of values C. Agreeing to practices and rituals which we do not practice D. Intellectually becoming aware of our own cultural heritage

The border between normal and expanded triplet repeat size for Huntington disease is about: A. 35 repeats B. 45 repeats C. 55 repeats D. 65 repeats E. 75 repeats

The concept that genetic counseling must be nondirective arises directly from respect for which of the following principles of medical ethics? A. Autonomy B. Justice C. Beneficence D. Paternalism

This syndrome is primarily due to trinucleotide expansions within the noncoding region of a gene. A. Fragile X syndrome B. Wolf-Hirschhorn syndrome C. Edwards syndrome D. Klinefelter syndrome E. Angelman syndrome

To establish a successful and cost-effective screening program for detecting heterozygous carriers of an autosomal recessive disease, all of the following are essential, EXCEPT: A. The screening test has a positive predictive value of 100% B. Reproductive options are available C. The disease is severe enough to be clinically significant D. A high-risk population can be identified E. Genetic counseling is provided with the testing

Ultrasonography of a 26-year-old woman at 16 weeks gestation shows fetal findings consistent with osteogenesis imperfecta, type II. The woman had a previous fetus affected with the same condition. The woman and her husband are healthy and have no obvious clinical characteristics of osteogenesis imperfecta. Which of the following is the MOST likely explanation for this recurrence? A. autosomal recessive inheritance B. de novo mutation C. germline mosaicism D. incomplete penetrance

What is the basis for genetic heterogeneity within tumor tissue? A. Each cell lineage may develop different sets of driver and passenger mutations. B. Tumor tissue has the same amount of genetic heterogeneity as normal tissue. C. The cancer originated in two different cells. D. Tumor tissue includes both normal and cancer cells, with all the cancer cells carrying the same set of mutations.

What is the major purpose of chemotherapy and radiation prior to surgery when it comes to cancer treatment? A. To shrink the tumor, allowing for less invasive surgical options B. To improve overall immune function C. To avoid surgical intervention altogether D. To determine which therapy will be most effective post-surgery

Which extracolonic tumor is NOT part of the Bethesda guidelines for Lynch syndrome? A. Breast cancer B. Stomach cancer C. Small bowel carcinoma D. Glioblastoma

Which of the following best defines first pass metabolism? A. Metabolism of ingested xenobiotics before the reach systemic circulation B. Activation of prodrugs through phase 1 metabolism C. Introduction of functional groups to provide substrate for Phase 2 metabolism D. Drug inactivation in the liver by CYPs

Which of the following features is NOT suggestive of a MSI-high colon tumor? A. Well-differentiated B. Mucinous C. Signet ring D. Tumor infiltrating lymphocytes E. Medullary growth pattern

Which of the following is NOT a hereditary risk factor for developing melanoma? A. previous history of a non-melanoma skin cancer B. Skin that always burns C. Red hair D. Blue eyes

Which of the following tumor types are most clearly associated with Von Hippel-Lindau disease (VHL)? A. Pheochromocytoma, endolymphatic sac tumors, hemangioblastoma B. Clear cell renal carcinoma, osteosarcoma, pancreatic adenocarcinoma C. Pancreatic islet cell tumors, hemangioblastoma, osteosarcoma D. Clear cell renal carcinoma, pheochromocytoma, glioblastomas E. All of these tumors are associated with VHL

Which of the following tumor types are most clearly associated with multiple endocrine neoplasia type 1 (MEN1)? A. Hyperparathyroidism, gastrinomas, pituitary adenomas B. Pancreatic islet cell tumors, papillary thyroid cancer, hyperparathyriodism C. Pheochromocytoma, hyperparathyroidism, pituitary adenomas D. Osteosarcomas, prolactinomas, carcinoid tumors

Which two of the following hereditary cancer syndromes are associated with an increased risk for radiation-induced malignancies? A. Li Fraumeni syndrome and retinoblastoma B. Cowden syndrome and Peutz-Jeghers syndrome C. Peutz-Jeghers syndrome Li Fraumeni syndrome D.Constitutional Mismatch Repair Deficiency and retinoblastoma

You assess that the family history in question 39 does NOT meet the Amsterdam II criteria for Lynch syndrome (LS). Why? A. There are not enough LS-associated cancers B. Betsy's history of polyps is concerning for FAP C. Her father was not diagnosed with rectal cancer until after age 50 years D. You were initially mistaken; this family actually meets the Amsterdam II criteria.

You would appropriately suspect a possible collagen disorder in a patient who has the following EXCEPT: A. progressive neurological deterioration B. blue sclerae C. rupture of the bowel D. joint hypermobility or laxity E. multiple fractures

Ehlers-Danlos syndrome

A group of inherited disorders that affect your connective tissues — primarily your skin, joints and blood vessel walls. -overly flexible joints and stretchy, fragile skin. This can become a problem if you have a wound that requires stitches, because the skin often isn't strong enough to hold them. -AD -thin nose, thin upper lip, small earlobes, weak aorta

Long QT Syndrome (LQTS)

A heart rhythm disorder that can potentially cause fast, chaotic heartbeats. Prolongation of QT waves/abnormality of T-waves - electrophysiologic disorder Ventricular tachycardia causing syncope (fainting)Cardiac arrest or sudden death50% untreated patients with pathogenic variants have symptoms Most common from preteens through 20sLQTS type 7 (Andersen-Tawil syndrome): muscle weakness and facial dysmorphism LQTS type 8 (Timothy syndrome): hand/foot, facial and neurodevelopmental features Jervell and Lange-Nielsen syndrome: profound sensorineural hearing loss20% do not have detectable pathogenic variants in one of 15 known genes Most AD except Jervall and Lange-Nielsen syndrome (AR)Small portion de novo Variable penetrance

unbalanced rearrangements

A rearrangement in which chromosomal material is gained or lost in one chromosome set

Ryan is a 2-year-old little boy whose parents bring him to the ER after watching him have a seizure. He has had some periods of apnea, the mother explains. What other features might you look for in ruling out a metabolic crisis? Check all that apply. A. hypothermia B. low pulse oxygen level C. organ dysfunction D. bradycardia

A,C,D

A 36-year-old male with moderate intellectual disabilities, large ears and hands is very shy and awkward in social situations and starts rocking and flapping his hands when he is upset. Which of the following is most likely his diagnosis? A. Fragile X syndrome B. Williams syndrome C. Down syndrome D. Hurler syndrome E. Rett syndrome

A 40-year-old man with neurofibromatosis (NF1) has a plexiform neurofibroma of his leg that has caused significant disfigurement, and hundreds of cutaneous neurofibromas. His 43-year-old sister has cafe-au-lait spots and Lisch nodules of the iris, but no neurofibromas. His 19-year-old son has cafe-au-lait spots, a dozen cutaneous neurofibromas, and scoliosis (curvature of the spine). Choose one of the following terms that best matches this clinical vignette. A. Variable expressivity B. Anticipation C. Incomplete penetrance D. Allelic heterogeneity E. Locus heterogeneity

A chromosomal analysis is obtained on a young woman with mild signs of Turner syndrome and reveals a 46,XX/45,X karyotype. Nondisjunction is most likely to have occurred in: A. mitosis after fertilization B. maternal meiosis I C. paternal meiosis I D. maternal meiosis II E. paternal meiosis II

A couple comes to you for counseling following the delivery of a stillborn fetus that had multiple anomalies 1 year ago. They would like to have another baby, but they are concerned about the possibility of recurrence. The couple declined autopsy after the fetus was delivered, but they bring you photos for review. You note a cleft extending diagonally across the face, a constriction ring around one arm, and multiple digital amputations on the ipsilateral hand with attached strands of tissue. Of the following, the MOST accurate statement regarding this condition is that it stems from an abnormality that usually occurs: A. In the first trimester B. At conception C. In association with chorionic villus sampling D. In the second or third trimester

A couple has a child with achondroplasia, but both parents have average stature. What is the best estimate of their chance of having another child with achondroplasia? A. Less than 0.1% B. 1-2% C. 25% D. 50% E. 100%

A couple has a child with severe osteogenesis imperfecta (OI) which was lethal at birth. The child was heterozygous for a point mutation in the COL1A1 gene. An unrelated friend, age 40, has mild OI which is also due to mutation in the COL1A1 gene. A. Allelic heterogeneity B. Locus heterogeneity C. Ascertainment bias D. Uniparental disomy E. Anticipation

A couple who recently had a daughter with a chromosome abnormality comes for genetic counseling. Their daughter's karyotype is 46,XX,del(3)(p25.3). Both parents are studied and their karyotypes are normal. The most pressing counseling at the moment would be: A. Although both parents have normal karyotypes, they could still have a small increased chance of having another child with an unbalanced karyotype due to the possibility of germ line mosaicism B. Small deletions do not usually cause severe birth defects or intellectual disability C. The parental chromosome testing should be repeated since one parent should have a balanced translocation to explain the deletion in the child D. The proband's phenotypically normal siblings should be karyotyped to determine if they are balanced translocation carriers

A genetic counselor is meeting with the parents of a newborn child with Down syndrome. When reviewing the pregnancy history, the father turns to the mother and yells, "This is your fault! I told you not to have those drinks over the holidays!" A. Confrontive B. Self-controlling C. Accepting responsibility D. Distancing

A man who has a family history of neurofibromatosis type 1 has a few café au lait spots, axillary freckling, and Lisch nodules. His daughter has severe scoliosis and at least a dozen large subcutaneous neurofibroma and is developmentally delayed. Which of the following concepts does this describe? A. Variable expressivity B. Allelic heterogeneity C. Incomplete penetrance D. Locus heterogeneity E. Lyonization

All of the following can cause variable phenotypes in urea cycle disorders except: A. level of exposure to sugars like glucose and fructose B. amount of residual enzyme activity C. variability in X-inactivation D. age of onset

At a follow-up appointment for the family of a newborn diagnosed with Trisomy 18, the genetic counselor asks the parents how they are doing. The father replies "Okay" to which the counselor responds, "Tell me what okay means to you." The counselor's response is an example of: A. Clarifying B. Redirecting C. Reflecting D. Rephrasing

Concerning genomic imprinting, which of the following statements is FALSE? A. Angelman syndrome affected patients are always due to uniparental disomy for chromosome 15 B. Prader-Willi and myotonic dystrophy syndromes exhibit features of genomic imprinting C. Deletions in chromosome 15 can cause Prader-Willi syndrome D. Lack of inheritance of a maternally derived chromosome 15 may cause Angelman syndrome E. A molar pregnancy occurs because of lack of sufficient maternal genetic material in the embryo

Sasha is a 13-year-old girl receiving treatment for small cell carcinoma of the ovary, hypercalcemic type. Sasha's past medical history is not significant prior to diagnosis. There is a paternal great uncle with prostate cancer diagnosed in his late 60's. Based on this information, should Sasha be referred to genetics for hereditary cancer risk assessment? A. Yes, Sasha's diagnosis warrants consideration of a germline predisposition and evaluation for a mutation in the BRCA2 gene given her diagnosis of the ovarian tumor and considering her great uncle's diagnosis of prostate cancer B. Yes, considering Sasha's ovarian tumor pathology and that she is less than 18 years of age, SMARCA4 testing is warranted regardless of family history C. No, in this case genetic evaluation should wait until Sasha reaches adulthood D. No, in this case it's most appropriate to recommend that Sasha's great uncle undergo his own genetic evaluation E. Yes, considering Sasha is under the age of 45 with an ovarian tumor, PTCH1 testing is warranted regardless of family history

The 33-year-old proband was identified to be an RB1 pathogenic mutation carrier. Should targeted testing be offered in this case for the proband's 4-year-old son? A. Yes, because ophthalmic screening can reduce morbidity in at-risk RB1 mutation carriers B. No, retinoblastoma rarely occurs beyond the age of 2 years C. No, RB1 DNA testing from a blood sample is not reliable and cannot be interpreted well D. No, a pediatrician should be able to recognize signs of retinoblastoma during routine well visits E. Yes, because there are no effective interventions to allow for early detection of ocular tumors

The best screening test will have which of the following? A. High sensitivity, high specificity, high positive predictive value B. High sensitivity, low specificity, high positive predictive value C. Low sensitivity, high specificity, high positive predictive value D. Low sensitivity, low specificity, low positive predictive value

The risk for the onset of serious mental illness can be estimated from known risk data and characteristics of a family, such as age at illness onset and of the individual for whom the risk is calculated. What issue would not apply to your discussion with a family about the risk for psychiatric disorders ? A. HapMap B. Liability/threshold model C. Jar model D. Polygenic inheritance

Trisomy 21 occurs when there is a normal diploid chromosomal complement but one extra chromosome 21. Although fertility is reduced in both sexes of individuals with Down syndrome, females have higher fertility than males. Given the fact that conceptuses with 48 chromosomes (four chromosomes 21) are not likely to survive early development, what fraction of surviving offspring would be expected to have Down syndrome if both parents have Down syndrome? A. One-half of the surviving offspring would be expected to have Down syndrome B. One-third of the surviving offspring would be expected to have Down syndrome C. -thirds of the surviving offspring would be expected to have Down syndrome. D. None of the surviving offspring would be expected to have Down syndrome E. All the children would be expected to have Down syndrome

What is the parental origin and stage of meiosis when most meiotic errors occur resulting in chromosomal trisomy? A. Maternal meiosis I B. Paternal meiosis I C. Maternal meiosis II D. Paternal meiosis II E. Maternal meiosis I and II are equally likely

Which is not a type of proto-oncogene? A. Mismatch repair genes B. Cell cycle regulator C. Growth factor receptors D. Nuclear transcription factors

Which of the following best describes the transfer of a fragment of chromosome 6p to chromosome 8q, and the transfer a fragment of chromosome 8q to chromosome 6p? A. Reciprocal translocation B. Deletion C. Inversion D. Isochromosome E. Robertsonian translocation

Which of the following can arise from unequal crossover, or can occur among the offspring of reciprocal translocation carriers? A. Duplication or deletion B. Isochromosome or deletion C. Uniparental disomy or duplication D. Inversion or isochromosome

Which of the following human diseases is least likely to be caused by aneuploidy? A. Fragile X syndrome B. Turner syndrome C. Down syndrome D. Patau syndrome E. Klinefelter syndrome

Which of the following is inherited in an X-linked recessive fashion? A. Lesch-Nyhan syndrome B. Tuberous scl.erosis C. San Filippo syndrome D. Rubenstein-Taybi syndrome

Which of the following is not a true statement regarding multiculturalism? A. Language is the only cultural barrier to communication in the medical setting B. To develop multiculturalism it is important to be aware of one's own cultural heritage C. Belief systems of a specific cultural group do not apply to all individuals in that cultural group D. It is important to clarify the word "family" for the counselor and patient as this term may have a different meaning to each culture.

Which of the following is true about GWA studies? A. They are useful for identifying genetic differences that have a smaller effect on the phenotype B. In order to focus in on a place in the genome that must be involved in disease risk, one must guess ahead of time what kind of gene to find C. They only account for a reasonably small number of discoveries in terms of the genetic risk factors for common disease D. They are not comprehensive enough to screen the entire genome for a disease gene

Which of the following is true of Tuberous Sclerosis? A. Loss of regulation of a kinase enzyme is thought to cause development of brain lesion cells B. There are almost never new mutations of either of these genes that cause TSC C. It is inherited in an autosomal recessive fashion D. The two associated genes, TSC1 and TSC2, must both have pathogenic variants in order to cause the disorder

Which of the following statements about FISH-based methods is true? A. FISH-based methods can be used to detect large deletions in chromosomes B. FISH-based methods detect missense mutations in genes C. FISH-based methods are used to detect trinucleotide repeat expansions in genes D. FISH-based methods cannot detect balanced chromosomal translocations

Which of the following statements about dispersed repetitive DNA is incorrect? A. A given repeat unit exists in the genome a number of times in tandem, but will not be interspersed throughout the genome, B. A given repeat is located in numerous, scattered locations in the genome C. They are transposable elements that can "jump" to new locations in the genome D. They are distinguished based on the size of the repeat units

You are doing a twin study, trying to determine the heritability of a given trait. Which of the following will be important in determining that there is significant heritability ? A. There is a higher incidence of disease in relatives than in the general population B. The concordance in your study is the same in monozygotic and dizygotic twins C. There is a cluster of the disorder in several families in your study D. Almost all of the twin pairs in your study grew up in a shared environment

NF1

AD Tumor Suppressor (2 hit), Ch. 17 NeuroFibromatosis type 1 or Von Recklinghausen's Ras GTPase activating protein (neuro bromin)

Li-Fraumeni Syndrome

AD inheritance Associated with MALIGNANCIES - Sarcoma - Breast cancer - Leukaemia - Adrenal gland syndrome Linked to germline mutations of p53 tumour suppressor gene

Alagille Syndrome

AD1 in 100,000Microdeletion of 20p12 corresponding to JAG1 geneFeats:- Cardiac: Peripheral PS, PS, TOF- Liver: Bile duct paucity (absence/marked reduction in number of interlobular bile ducts)- Facies: Broad forehead, deep-set widely spaced eyes, long straight nose, short pointed chin- Vertebral: Butterfly vertebrae, fused vertebrae, spina bifida occulta

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)

AKA Osler-Weber-Rendu disease AD with several known genes (ENG, ACVRL1,SMAD4, GDF2)Arteriovenous malformations - arterial vessels flow directly into the veins rather than into the capillaries. - extra pressure strains these veins Telangiectasias - red markers Compression or irritation of adjacent tissues with frequent hemorrhages Nose bleeds Hemorrhages in brain, liver, lungs, and other organs Type 1: symptoms develop earlier w/ blood vessel malformations in the lungs and brain Type 2 and 3 may have higher risk of liver involvement Juvenile polyposis/HHT syndrome involves arteriovenous malformations & GI polyps

Familial adenomatous polyposis and AFAP

APC gene AD hundreds to thousands of precancerous colorectal polyps (adenomatous polyps) Can lead to cancer of left untreated Desmoid tumors AFAP (attenuated FAP) fewer polyps (average of 30) and later age of onset of polyps and cancer than is typically seen in classic FAP

Friedreich ataxia

AR inheritance -AAG repeat in frataxin (nuclear mito gene chrom. 9), FRDA, in intronusually 100-1200 copiesincoordination of limbs, apraxia, absent DTR, neuropathy, cardiomyopathy, foot deformities and scoliosis, type 2 diabetes

homocystinuria

AR, cystathionine synthase deficiencyaminoacidopathytreatable with pyridoxinesome overlap with Marfan syndrome: dislocation of lens, long bones. Other features thromboembolism, osteoporosis, ID

Cystic Fibrosis

AR; 7q31 CFTR gene - affected movement of salt in and out of the body 70-80% of carriers have the change F508 mutation (c.1521_1523delCTT) Incidence 1/2000-1/3000 - most common in Caucasians Causes thick, sticky mucus in respiratory, digestive, and reproductive Plugs up tubes, ducts and passageways - pancreatic fxn impaired Increased salt in sweat - earliest signs - sweat test Leading cause of bronchiectasis Affected individuals get chronic infections Male infertility - vas deferens blocked with mucus or missing entirely Some females may have reduced fertility and symptoms may be worse during pregnancy Increased heart rate, fatigue, weakness and low blood pressure

Familial thoracic aortic aneurysm (FTAAD)

Affects thoracic part of the aorta, near the heart, arteries can also be affected Aortic dilation can lead to aneurysm or dissection Generally aortic dilation is the first features In some, dissection occurs with little or no aortic dilation May be only symptom, but some show mild features related to Marfan/Loeys Dietz) Aortic abnormalities can begin in childhood Accounts for over 20% of thoracic aortic dissection/aneurysm, cause almost 30,000 deaths in the US annually Remainder result from damage to aorta from aging, tobacco use, injury, or disease Mutations in ACTA2 gene = 14-20%; TGFBR2+2.5%; other genes - smaller percentage of cases AD with reduced penetrance Regular screening in FDRs (first degree relatives) should include EKG, MRI, or CT scan and the aortic root may need to be replaced

Your patient is a 25-year-old woman who is at 50% risk to inherit a RET mutation from her mother. The RET mutation is V804M, which is a level A mutation (lowest risk category). Which of the following is/are appropriate to offer the patient? A. Predictive RET testing B. Prophylactic thyroidectomy if she is a mutation carrier C. Annual screening using thyroid ultrasound and measurement of calcitonin levels if she is a mutation carrier D. Annual screening using plasma metanephrines if she is a mutation carrier E. Annual screening using calcium and parathyroid hormone (PTH) if she is a mutation carrier F. All of these options are appropriate

All of the above

Given the following symptoms, which of these combinations best reflects the phenotype of a long-chain fatty acid oxidation defect? 1. muscle pain 2. lethargy/confusion 3. congestive heart failure 4. myoglobinuria 4 only 1 and 3 2 and 4 all of these are correct 1, 2 and 3

All of the above are correct

what skin lision is common in multiple endocrine neoplasia 1

Angiofibromas

A woman with advanced breast cancer has an appointment with the genetic counselor and her oncologist. The genetic counselor calls the woman before the appointment to obtain and review the family history. At that time, the woman abruptly states she does not need genetic counseling because she will be fine and wishes to cancel the appointment. This is an example of: A. Distancing B. Escape-avoidance C. Plan D. Positive reappraisal

Affected individuals with this syndrome could have a microdeletion present in 4p. A. Fragile X syndrome B. Wolf-Hirschhorn syndrome C. Edwards syndrome D. Klinefelter syndrome E. Angelman syndrome

Renal Disorders Examples

Autosomal Dominant Polycystic Kidney Disease (ADPKD), Autosomal Recessive Polycystic Kidney Disease (ARPKD), Alport syndrome, Renal Tubular disorders

Juvenile polyposis syndrome

Autosomal dominant syndrome in CHILDREN [> 5] featuring: 1. Numerous hamartomas in colon, stomach, small bowel 2. Associated w/ ↑ risk of CRC

A couple presents for a prenatal consultation at 28 weeks' gestation. After reviewing basic information about your practice, the wife explains that she is one of six children, four of whom are currently alive. She had a sister and a brother who both died between the ages of 3 and 4 years. Although normal at birth, both children had progressive loss of milestones beginning at about 1 year of age, with hypotonia and later severe muscle weakness, difficult-to-control seizures, visual loss, and eventual death. No other individuals in the extended family had such problems. The woman is concerned about this family history and wishes to know possible risks for her children as well as advice about testing for her newborn. Of the following, you are MOST likely to tell her that her affected siblings probably had: A. An autosomal dominant condition with incomplete penetrance, and the risk to her unborn child may be as high as 50% B. An autosomal recessive condition, and the risk to her unborn child is probably low C. A mitochondrial condition, and the risk to her unborn child may be as high as 100% D. An X-linked recessive condition, and the risk to her unborn child may be as high as 50% if she gives birth to a son

A phenocopy is A. A genetic trait which mimics a non-genetic one B. A non-genetic trait which mimics a genetic one C. A specific physical feature of a genetic syndrome D. None of the above

Some of the most important improvements that paired DNA/RNA sequencing adds to traditional testing include all of the following EXCEPT: A.It can increase detection without increasing the inconclusive rate B. Alternative splicing creates only one functional protein per RNA transcript C. It can improve variant detection/classification independent of personal history D. It identifies more high-risk cancer patients than DNA sequencing alone

Which are the two tumors MOST predictive for a P53 mutation? A. Acute leukemias and early onset breast cancer B. Childhood onset adrenal cortical carcinoma and choroid plexus brain tumors C. Sarcomas and acute leukemias D. Glioblastoma multiforme and childhood onset adrenal cortical carcinoma E. Acute leukemias and choroid plexus brain tumors

amie is a 34-year-old woman with bilateral carotid body paragangliomas and a recently identified SDHD mutation, who comes to you for counseling. There is no known family history of paragangliomas or pheochromocytomas. She has a son, age 10, and a daughter, age 12. Her brother is 32 years old and in good health. He also has a 10-year-old son. Jamie's parents are both 60 years old and healthy. She has three paternal aunts who died at 65, 56, and 72, with no history of paragangliomas. In addition, she has several paternal first cousins with no evidence of cancer or tumors. Jamie's paternal grandparents are alive and well in their 70s. Jamie's mother is an only child and her maternal grandparents died young in an accident. Jamie wonders how she could have a hereditary condition if she has no family history of paragangliomas. Which of Jamie's grandparents most likely had the SDHD mutation? A Paternal grandfather B. Paternal grandmother C. Maternal grandmother D. It's impossible to know without genetic testing E. None of them are likely to be carriers - Jamie probably has a de novo mutation

hat are the four phases of carcinogenesis? A. Initiation, progression, latency, metastasis B. Initiation, promotion, progression, metastasis C. Initiation, progression, metastasis, cell death D. Initiation, mutation, promotion, metastas

A 22 year old woman who is 20 weeks pregnant had a fetal ultrasound which showed spina bifida and slightly enlarged cerebral ventricles. After the genetic counselor discusses the possible diagnosis and the unpredictability of the outcome, the woman expresses her reluctance to terminate the pregnancy. Her partner remains very quiet and says that he will go along with his partner's decision. Which is the BEST approach for the genetic counselor to take? A. Support the woman's decision B. Engage the partner in the decision-making process C. Refer the couple for family therapy D. Suggest that the couple continue this discussion at home.

A 24-year-old woman with myotonic dystrophy has significant muscle weakness and wasting. She has a one-year-old son with very poor muscle tone and severe weakness and significant developmental delay. Her affected 55-year-old father has cataracts but no muscle weakness. Choose one of the following terms that best matches this clinical vignette. A. Variable expressivity B. Anticipation C. Incomplete penetrance D. Allelic heterogeneity E. Locus heterogeneity

A child is born with a partial deletion and partial duplication involving the same chromosome. Which of the following parental chromosomal abnormalities is most likely to lead to this occurrence? A. paracentric inversion B. pericentric inversion C. balanced Robertsonian translocation D. isochromosome

A patient was prescribed lithium by her psychiatrist. She began taking this medication in the first trimester prior to pregnancy recognition and is now concerned about fetal risks. The fetus is at increased risk for which of the following? A. Neural tube defect B. Ebstein's anomaly C. No risk, lithium is not associated wiht adverse fetal outcome D. Growth restriction E. Chromosome anomaly

A ten-month old child develops bilateral retinoblastoma. In this child, is the occurrence of retinoblastoma more likely to be sporadic or inherited? A. There is no way to tell from the information provided B. Inherited C. Sporadic

A woman has a son with Duchenne muscular dystrophy, and he is the only affected individual in the family. He is found to have a deletion of exon 53 in DMD, and the woman had her daughter from a previous marriage are requesting DNA testing. When the studies are completed, the laboratory issues a report stating that the deletion was not found in either woman. Which of the following conclusions is accurate? A. Neither the mother nor the daughter are at increased risk for having an affected child B. The mother may be at increased risk but the daughter is not C. Both may be at increased risk D. The mother's sisters are at increased risk of being carriers E. B and D

A young boy has an autosomal dominant condition. Neither of his parents (who are unrelated to each other) has any clinical features of this condition, but his maternal grandmother is similarly affected. This is an example of A. Germ line mosaicism B. Incomplete penetrance C. Anticipation D. Spontaneous mutation E. Locus heterogeneity

About 70% of all polyps are characterized as adenomas, with the other 30% being made up of other polyp types. Which of the following involves a sessile type of polyp? A. Leiomyoma B. Villous adenoma C. Tubular adenoma D. Hamartoma E. Inflammatory

All of the following karyotypes are found in spontaneous abortuses. Which of the following is least likely to be found in a live-born infant? A. 47,XX,+21 B. 47,XX, +16 C. 45, X D. 69,XXX E. 46,XY

Disorders observed exclusively or almost exclusively in living females but not in males include all of the following except: A. Aicardi syndrome B. McCune-Albright syndrome C. Goltz syndrome D. Incontinentia pigmenti E. Rett syndrome

If a patient was not responding normally to Warfarin therapy due to PGx interactions, which of the following genes should they be tested to have genetic variants of? A. CYP2C19 only B. CYP2C9 and VKORC1 C. VKORC1 only D. SERT and CYP2C19

In a counseling session for presymptomatic BRCA1 testing, you make the statement: "Sometimes people feel anxious about their own health after a positive result. Let's go over the things you can do to take care of yourself if that happens." A. Empathy B. Anticipatory guidance C. Immediacy D. Normalization

In the multistep model of colorectal carcinogenesis, what is the correct order of progression? A. Loss of heterozygosity at 18q > late adenoma > formation of aberrant crypt foci > carcinoma B. Formation of aberrant crypt foci > activation of KRAS proto-oncogene > late adenoma > carcinoma C. Loss of heterozygosity at 18q > early adenoma > activation of KRAS proto-oncogene > carcinoma C. Early adenoma > formation of aberrant crypt foci > carcinoma > late adenoma

Regarding Marfan syndrome, which of the following statements is true? A. If a child does not fulfill diagnostic criteria for Marfan syndrome, that child will never develop related symptoms at a later date B. Dominant negative point mutations cause Marfan syndrome c. Marfan syndrome is only diagnosed in individuals who are both tall and thin D. Different severities of medical complications in Marfan patients are primarily due to effects of genetic anticipation E. Marfan syndrome is typically only seen in a single sibship and not transmitted from generation to generation

Retinoblastoma usually occurs as a sporadic event, but in around 10% of cases there is a positive family history due to autosomal dominant inheritance. In these families, the penetrance is approximately 80%. A woman with retinoblastoma, whose father and grandfather were also affected, has an unaffected partner with no relevant family history. Which of the following is correct regarding their children? A. The probability that their first child will be affected is 0.25 B. The probability that their first child will be affected is 0.4 C. The probability that each of their children will be affected is 0.5 D. The probability that each of their children will be affected is 0.4 multiplied by 0.5

What is the approximate incidence of Lesch-Nyhan syndrome? A. 1/2000 livebirths B. 1/380,000 livebirths c. 1/220,000 livebirths D. 1/1000 pregnancies, but only 1/4000 livebirths due to prenatal loss

Which of the following chromosome abnormalities occurs only during meiosis II? A. 45,X B. 47,XYY C. 47,XXY D. 47,XXX

Which of the following is NOT a feature of Rubenstein-Taybi syndrome? A. Broad thumbs B. Frontal bossing C. Short stature D. Moderate to severe learning disabilities

Which of the following is NOT a necessary biologic capability of metastatic cancer cells? A. De-differentiation B. Deactivation of HLA receptors C. Bypass cell cycle checkpoints D. Avoid programmed cell death

Which of the following is NOT an appropriate interviewing technique for a genetic counseling session? A. Asking open-ended questions, which invite the client to indicate what is relevant to them B. When working with couples posing questions to only one of the clients, which helps prevent other client's agenda from interfering with the session. C. Rephrasing, which allows the counselor to clarify that both he/she/they, understands the client's concern D. Asking close-ended questions, which clarify specific details.

Which of the following is NOT correct about Fragile X syndrome? A. A pre-mutation is comprised of 55-200 CGG repeats B. Females cannot be as affected as males C. The hallmark features of Fragile X include a long face, prominent ears, and enlarged testicles D.Fragile X pre-mutations in almost all cases will only expand when passed down maternally

Which of the following is not a well-known trigger for high blood ammonia levels? A. a virus/infection B. low protein diet C. dehydration D. excessive exercise E. prolonged fasting

Which of the following statements about multifactorial disease is false? A. Multifactorial inheritance can explain why siblings in a family may or may not be affected by a particular trait, such as cleft lip B. Pyloric stenosis is an example of a quantitative trait C. Higher heritability for a trait would imply that monozygotic twins are more likely to both be affected than would dizygotic twins D. Multifactorial inheritance refers to the impact that genes and environment have upon a given phenotype or trait E. The risk to the proband is higher if multiple other family members are affected

Which of the following statements is false regarding some of the molecular mechanisms underlying genetic diseases? A. Expanded numbers of trinucleotide repeats are present in the protein coding region of patients affected by Huntington disease B. A male affected by Prader-Willi syndrome due to 15q11 deletion would generally be sterile, but hypothetically if he has a female child that inherited the deleted chromosome, the child would have Angelman syndrome C Myotonic dystrophy is an autosomal dominant disorder with pedigrees demonstrating genetic anticipation D. Recessively inherited genetic diseases can demonstrate genetic anticipation E. Beckwith-Wiedemann syndrome can be due to overexpression of the insulin-like growth factor 2 gene

Which of the following statements regarding molecular testing methods is false? A. FISH-based methods can be used to detect deletions that cause Prader-Willi syndrome B. Chromosome paints generally allow for identification of frame-shifting point mutations C. Currently, the evaluation of RNA expression levels of thousands of individual genes in a tissue sample can be simultaneously assayed by array technologies D. Direct DNA sequence of certain genes is clinically available

Which of the following statements regarding mutations causing Huntington disease is FALSE? A They typically involve expansion of trinucleotide repeat units B. Trinucleotide repeat units are located within the 3' untranslated region of the HD gene C. Mutations are considered to be gain-of-function D. Expansion is more likely to occur when the repeat is inherited from the father E.The larger the expansion, the younger an individual may manifest symptoms

You are called to examine a newborn girl who has multiple congenital anomalies. On physical examination, you notice several "punched-out" scalp ulcers, bilateral cleft lip and palate, postaxial polydactyly (extra digit on the ring finger side) of the hands, and a small omphalocele. Of the following, this infant's karyotype MOST likely is: A. 47, XX + 18 B. 47, XX + 13 C.45, X D. 45, X/ 47, XXX

You are seeing a couple in your clinic who is pregnant with their first child. On the referral form it says, "fetus at risk for pyloric stenosis. Parent affected." You contract with the couple, and they are clearly interested in knowing what the recurrence risk will be for their current pregnancy. Which of the following situations would lead to the greatest risk ? A. It was the wife who was affected and the current pregnancy is known to be female B. It was the wife who was affected and the current pregnancy is known to be male C. It was the husband who was affected and the current pregnancy is known to be female D. It was the husband who was affected and the current pregnancy is known to be male

which of the following is most likely to be associated with Muir-Torre syndrome? A. Sebaceous hyperplasia in the head/neck B. Sebaceous adenoma in the head/neck area C. Sebaceous hyperplasia on the trunk/limbs D. Sebaceous adenoma on the trunk/limbs

Which of the following statements correctly describes events that occur in meiosis? A. DNA replication occurs in both interphase I and interphase II B. The pachytene stage of prophase I is when crossing over occurs C. Recombination only occurs in meiosis I of oogenesis, not spermatogenesis D. In metaphase I of meiosis, the chromosomes line up "single-file" E. In anaphase I of meiosis, the centromeres divide to separate the sister chromatids

B. The pachytene stage of prophase I is when crossing over occurs

Juvenile polyposis syndrome

BMPR1A and SMAD4ADmultiple noncancerous (benign) growths called juvenile polyps criteria one or more of the following (1) more than five juvenile polyps of the colon or rectum (2) juvenile polyps in other parts of the gastrointestinal tract (3) any number of juvenile polyps and one or more affected family members10-50% chance of developing cancer

What DECREASES the likelihood that an individual with colon cancer will have Lynch syndrome?

BRAF and KRAS mutations

Pathogenic variations in which gene leads to the HIGHEST ovarian cancer risk?

BRCA1

BRCA1/2

BRCA1/2ADHigh risk breast and ovarian cancer also associated with pancreas, male breast, prostate

Gorlin syndrome

Basal cell nevus syndrome Medulloblastoma Dural calcifications Basal cell skin cancer after radiation Odontogenic keratocysts

Panel testing has identified homozygous PMS2 mutations in the affected children confirming a diagnosis of constitutional mismatch repair deficiency (CMMRD) and the parents as likely PMS2 mutation carriers and as having Lynch syndrome. The parents also share how they have an 8-year-old unaffected girl (who does not have cancer, but genetic testing has not been done yet), At what age is screening recommended for their unaffected daughter?

Because the child is at 25% risk, it should begin immediately following a positive diagnosis

Believe it or not, your current client reminds you of your mother. Every time you meet in session with this client, you start thinking about all of those unresolved issues you have with Mom and you catch yourself watching the clock on the wall behind the client, wishing the session would end. In fact, you are starting to dislike this client and are considering terminating and referring her to another counselor. Chances are you are experiencing: A. Guilt versus initiative B. Parental interjections C. Countertransference D. Transference

An 8-year-old boy was found to have a heart defect just after birth and has been followed by cardiology. The family recently moved, however, and transferred care to a new cardiologist who noticed that the child has some unusual physical features. Accordingly, the cardiologist referred the child to genetics for an evaluation. During a physician exam, the child was observed to have shorter stature, one café au lait macule, hypospadias and slightly hypoplastic thumbs, bilaterally. The genetic counselor immediately recognized this constellation of features and sent a screening test for confirmation, which came back positive. During counseling, it is important to inform the family that the child will be at increased risk to develop:

Bone marrow faliure

A 2-year-old male child has been referred to you because he has autism, more than 8 café-au-lait spots greater than 1.5 centimeters, macrocephaly, fifth finger clinodactyly, and an ear tag. Which of the following statements is false? A. This child does not meet diagnostic criteria to assign a diagnosis of NF1 at this time B. This child could be diagnosed with NF1 at this time if one of his biological parents is confirmed to have NF1 C. This child will not have a chromosome anomaly upon karyotype analysis, so it should not be performed D. This child could have Fragile X syndrome E. This child could develop additional physical signs of NF1 as he gets older, confirming a diagnosis of NF1 at that time

A patient with an Ashkenazi Jewish BRCA1 mutation is seen in your clinic. She is very anxious about testing her adult children, because they have Ashkenazi Jewish ancestry on their father's side as well. Which of the following testing should you recommend for her children? A. Single-site testing for the known mutation in your patient B. Comprehensive BRCA1 and BRCA2 testing C. Multi-site 3 BRCA testing D. Panel testing for breast cancer genes

How do cytoxic agents work? A. They target surface hormone receptors. B. They incorporate DNA sequences into the cancer cell's genome. C. They prevent cells from dividing, leading to eventual cell death D. hey mark the cancer cells for targeting by the immune system.

In the African-American population, sickle cell anemia occurs in about 1/400 individuals. What is the approximate carrier frequency of sickle cell anemia in this population? A. 1/400 B. 1/160,000 C. 1/10 D. 19/20 E. ¼

Pyloric stenosis is a multifactorial condition in which males have a significantly lower threshold for being affected than females. Therefore, there is a preponderance of males affected relative to females. Of the following individuals, which would be least likely to manifest the disease? A. Brothers of affected males B. Brothers of affected females C. Sisters of affected males D. Sisters of affected females E. Brothers and sisters of affected females have equal risks

The genetic counselor is meeting with a family at a six-month follow-up appointment for their child with Angelman syndrome. At the first meeting, the genetic counselor recalls that the father was tearful and expressed his grief at the loss of having a "normal" child. At the current appointment, the father discusses his difficulties with sleep and lack of interest in engaging with wife and child. Which is the most appropriate intervention? A. Do nothing. This is a normal response. B. Refer him to an internet site with information about Angelman syndrome C. Refer the patient for mental health services D. Shift attention to the mother to determine how she is coping

This syndrome is due to the presence of an autosomal trisomy. A. Fragile X syndrome B. Wolf-Hirschhorn syndrome C. Edwards syndrome D. Klinefelter syndrome E. Angelman syndrome

Which fetal karyotype, detected by prenatal diagnosis, would warrant karyotyping the parents? A. 47,XXY B. 45,X C. 46,XX,t(1:10)(p13;q12) D. 47,XY,+21E. 69,XXX

Which of the following are the three BRCA1 and BRCA2 gene mutations associated with Ashkenazi Jewish ancestry? A. 1100delC, 5385insC, 953insA B. 187delAG, 834delT, 1100delC C. 5385insC, 187delAG, 6174delT D. 953insA, 834delT, 2300insG

Which of the following conditions is NOT associated with hamartomatous gastrointestinal polyps? A. Peutz-Jeghers syndrome B. Cowden syndrome C. MYH-associated polyposis D. Juvenile Polyposis syndrome

You are meeting with a woman for genetic counseling due to a history of multiple miscarriages. When planning your approach for the case, which is the most effective, and direct way to understand how your client is dealing with her multiple losses? A. Take the family and medical history to develop a rapport with your client B. Review the available medical records , looking for documentation of depression C. Ask your client to tell you the "story" of what brings her in for genetic counseling D. Assume that the client experienced grief for several weeks after each loss, but has returned to her pre-crisis level of functioning.

You meet with your client, Ms Garcia, to discuss testing for a family-specific BRCA1 mutation. During the session, you say, "I have had many people tell me that they feel a sense of guilt about passing a cancer mutation to their children." This is an example of: A. Anticipatory guidance B. Empathy C. Normalization D. Confrontation

hich of the following account for the grand majority of cancer diagnoses? A. Leukemias and lymphomas B. Sarcomas C. Carcinomas D. Neuroectodermal tumors

inkage is a violation of which of the following genetic concepts: A. Mendel's Law of Segregation B. Recombination C. Mendel's Law of Independent Assortment D. Hardy Weinberg Equilibrium

Which of these is a type of Mendelian inheritance? A. Mitochondrial B. Multifactorial C. Y-linked D. Contiguous gene syndrome

A 35 year-old woman, recently diagnosed with an invasive ductal carcinoma of the breast, comes for genetic counseling with her 30-year-old sister. Their mother died of breast cancer at age 52 and was the only other affected relative. To determine the risk to her daughter, the woman has comprehensive BRCA1 and BRCA2 genetic testing with negative results. Which of the following statements by this patient should make the counselor MOST concerned that she does not fully understand these results? A. "I am not at significantly increased risk for ovarian cancer" B. "My daughter will not need to have BRCA testing" C. "My sister is not at increased risk for breast cancer" D. "I am considering bilateral mastectomy"

A 35-year-old woman comes for genetic counseling because of a family history of polycystic kidney disease (PKD) consistent with autosomal dominant inheritance and confirmed by review of medical records. Genetic testing has not been performed. The woman's renal ultrasound showed a single, unilateral, kidney cyst. The patient states, "Now that I have PKD, my children are at 50% risk to have it too. They need to have DNA testing." Which of the following is the best response to the patient's statement? A. Agree that she meets diagnostic criteria and recommend her children have DNA testing B. Agree that she meets diagnostic criteria and recommend her children have renal ultrasounds C. Explain that she does not meet diagnostic criteria and recommend an affected relative have DNA testing D. Explain that she does not meet diagnostic criteria and recommend she have DNA testing

A genetic counselor working with multiple individuals from the same family accidentally mentions that she has met with another relative while collecting the family history. This is a violation of that relative's A. Autonomy B. Consent C. Confidentiality D. Privacy

A girl with short stature undergoes chromosome analysis because of the suspicion she may have Turner syndrome. She has normal female external genitalia. Her karyotype is mos45,X/47,XYY. No other cell lines are observed. What is the most likely karyotype of the fertilized egg from which she developed? A. 45,X B. 46,XX C. 46,XY D. 47,XYY E. 47,XXY

A metabolic screen includes all but which of the following? A. urine organic acids B. blood amino acids C. a sweat test D. blood acylcarnitines

A patient reports having been exposed to a teratogen during her 11th week of pregnancy. What problem might the fetus be at increased risk for? A. Neural tube defect B. Heart defect C. Intellectual disability D. Cleft lip E. Limb reduction defect

A woman has a 2-year-old male child recently diagnosed with Duchenne Muscular Dystrophy (DMD). Which of the following is false? A. She could have another male child affected by DMD B. The child may not have inherited the DMD mutation C. If a DMD gene mutation is found in the child, but not in the mother, then there is no chance that DMD could recur in this family D. The child could have a male sibling that is younger and who has not manifested symptoms of DMD but also has the mutated gene E. Most mutations in the DMD gene are large deletions or duplications detectable by a multiplex-PCR approach

A young woman in the end stages of ovarian cancer requests genetic testing. Her doctor orders a breast cancer panel and a mutation in the BRCA2 gene is identified. She passes away before the results are obtained. Her husband, as next of kin is contacted by his wife's physician for results disclosure. He states that he does not want to know his wife's results and he refuses to give his permission to release the results to his wife's biological sister. They physician never the less feels obligated to warn his patient's sister in order to prevent harm. The physician is more likely following which ethical principle? A. Autonomy B. Paternalism C. Nonmaleficence D. Maleficence

A young woman of northern European descent is the single parent of a child with autosomal recessive cystic fibrosis. She marries her first cousin and becomes pregnant. What is the probability that her child will have cystic fibrosis? A. 1/2500 B. 1/100 C. 1/32 D. 1/8

After disclosure of a positive result for BRCA1 mutation, the genetic counselor encourages the woman to consider sharing the family history and test results with her adult daughter. One week later, the genetic counselor receives a phone call from the patient who yells that her daughter is no longer speaking with her and does not want to know if she has inherited the mutation. She states that the genetic counselor has ruined her relationship with her daughter. What is the genetic counselor's best response? A. Allow for some silence in order to give the patient an opportunity to calm down. B. I think you may be angry with your daughter over her decision. Can I help to facilitate a discussion between the two of you? C. This must be very upsetting for you. Can you tell me more about what happened when you disclosed your results to your daughter? D. Your daughter is making an unwise decision and should reconsider given her 50% risk to have inherited the mutation.

Amy comes for a genetic counseling appointment after learning that her brother has been found to have multiple colon polyps (>20). Her mother is living, age 60, with no polyps. Her father died in his 40s of heart disease, and she has no other siblings. Who is the most appropriate candidate to undergo genetic testing? A. Amy B. Amy's mother C. Amy's brother D. Any of the family members described in the question

Concerning genomic imprinting, which of the following statements is false? A. Deletions in chromosome 15 can cause Prader-Willi syndrome B. A molar pregnancy occurs because of lack of sufficient maternal genetic material in the embryo C. Angelman syndrome affected patients are always due to uniparental disomy for chromosome 15 D. Lack of inheritance of a maternally derived chromosome 15 may cause Angelman syndrome E. Prader-Willi and myotonic dystrophy syndromes exhibit features of genomic imprinting

If a chromosome is symbolized as ABCDEFG, which of the following would be considered an inversion? A. GEFCDAB B. ABCEFGD C. ABEDCFG D. FGCBADE E. CBAGFED

In a family with mitochondrial disease, which of these individuals is least likely to show features? A. The son of an affected female B. The son of a woman's whose mother is affected C. The daughter of a man's whose mother is affected D. The daughter of a woman's whose mother is affected E. The daughter of an affected female

Regarding conditions potentially attributed to multifactorial inheritance patterns and the liability/threshold model, which of the following statements is true? A. Incidence of the condition will be higher in relatives of the less severely affected patients B. Recurrence of a congenital anomaly in a family is always due to dominant, recessive, or X-linked inheritance of a single mutated gene C. If more than one relative is affected, the risk for other members of the family to be affected is increased D. Familial clustering of diabetes, hypertension, and ischemic heart disease is not due to multifactorial inheritance patterns E. The recurrence risk for a condition will be the same for males or females, if the condition is subject to gender-dependent thresholds of liability

The average recurrence risk for a couple that has had a child with cleft lip, a multifactorial birth defect, is approximately 4%. What is the recurrence risk if the couple has two affected children? A. 2% B. 4% C. 10% D. 25% E. 50%

The condition known as cri-du-chat syndrome in humans has a genetic constitution designated as ________. A.heteroplasmy B. trisomy C. 46, 5p- D. 45, X E. triploidy

The genetic counselor is meeting with a couple pregnant with their second child. While reviewing the family history, the couple disclosed that their first child was born with a cleft lip. The mother explains to the counselor that she originally did not want to keep the first pregnancy and the cleft lip is a punishment for considering termination. What emotional response is the mother expressing? A. Despair B. Shame C. Guilt D. Denial

Two brothers marry two sisters. One couple has a child with Hurler syndrome. No other family members are affected. What is the risk for the other couple having a child with the same condition? A. ¼ B. 1/9 C. 1/16 D. 1/32 E. Need to know the incidence in the general population to estimate the couple's risk

Tyler is a 3-year-old boy diagnosed with a rhabdomyosarcoma. Prior to obtaining any information about his family history, all of the following would be in your differential diagnosis EXCEPT: A. Beckwith-Wiedemann syndrome B. Costello syndrome C. Diamond-Blackfan anemia D. DICER 1 syndrome

Which individual has the highest risk of having abnormal offspring? A. A carrier of a paracentric inversion B. A carrier of a pericentric inversion C. A carrier of a Robertsonian 21q21q translocation D. A carrier of a balanced reciprocal translocation

Which karyotype would be MOST frequently seen in liveborn infants (as opposed to spontaneous abortions)? A. 47,XX,+3 B. 69,XXX C. 47,XX,+21 D. 46,XY,-11,+22 E. 46,YY

Which of the following cytogenetic results listed below indicate that the child in question has Down syndrome? A. 47,XX,+22 B. 46,XY,t(2;21)(q13;q21)pat C. 46,XY,+21,der(21;22)(q10;q10)D. 45,XX,der(14;21)(q10;q10)mat E. 46,XX.ish del(21)(q22.3q22.3)(D21S65-)

Which of the following is NOT true about X-Inactivation? A. It involves altered chromatin structure B. It involves differential methylation of DNA C. Up to 40% of all X-linked genes escape inactivation in some way D. CpG islands in silenced genes are methylated The X-inactivation center is located at Xq13.2

Which of the following is NOT true about polygenic traits? A. They are caused by a combination of variations in many genes B. They are caused by genes with additive effects C. Within the normal distribution curve, no more than about 90% of the population will fall within the curve D. The spread of the distribution around the mean is determined by standard deviations

Which of the following is not a characteristic of DiGeorge syndrome? A. Affected individuals have a deletion of chromosome 22q11 B. Heart defects frequently observed in affected individuals C. Affected individuals may have hypercalcemia D. Immune deficiency can occur due to thymic hypoplasia E. Schizophrenia is known to occur in some individuals

Which of the following is not a characteristic of Williams syndrome? A. Most cases are due to a microdeletion within chromosome 7q B. Heart defects are observed in affected individuals C. Involvement of the fibrillin gene at chromosome 7 is responsible for many of the clinical features D. A normal karyotype in a suspected case would not rule out Williams syndrome E. Features include periorbital fullness, full lips, high pitched voice, and sometimes, a proclivity to music

Which of the following is not a feature of a metabolic crisis? A. movement disorders such as dystonia B. seizures C. brain bleeds D. diffuse hypotonia E. ataxia

Which of the following patients is MOST likely to have an MMR mutation associated with Lynch syndrome? A. 45-year-old woman with endometrial cancer, whose mother had ovarian cancer at age 67 B. 45-year-old woman with endometrial cancer, whose mother had endometrial cancer at age 67 C. 45-year-old woman with synchronous endometrial and colon cancer D. 45-year-old woman with synchronous endometrial and ovarian cancer

Which of the following would be true for a couple in which both members have Down syndrome? A. One-half of the surviving offspring would be expected to have Down syndrome. B. One-third of the surviving offspring would be expected to have Down syndrome. C. Two-thirds of the surviving offspring would be expected to have Down syndrome D. All the children would be expected to have Down syndrome. E. None of the surviving offspring would be expected to have Down syndrome.

You are asked to consult on a baby in the neonatal intensive care unit who has severe respiratory distress and unusual physical features. The baby is receiving maximum ventilatory support, but his oxygen saturation is in the 80s. His nose is deviated to one side, his ears are overfolded, and his hands and feet are unusually positioned. You review his chest radiographs and note bilateral pulmonary hypoplasia. Of the following, the test that is likely to be MOST helpful in determining the cause of this infant's abnormalities is: A. Toxicology screen B. Echocardiography C. Renal ultrasonography D. Chromosome analysis

This syndrome can be caused by a lack of maternally derived chromosome 15q11. A. Fragile X syndrome B. Wolf-Hirschhorn syndrome C. Edwards syndrome D. Klinefelter syndrome E. Angelman syndrome

Chemotherapy is the primary strategy to treat CRC true or false?

False

A 32-year-old woman presents to clinic given her personal history of melanoma diagnosed on her arm at the age of 28 and on her leg at the age of 30. Her family history is significant for pancreatic cancer diagnosed in her mother at the age of 53, melanoma diagnosed in a maternal aunt in her 20s, and pancreatic cancer diagnosed in a maternal uncle in his 60s. What gene would you consider offering testing for?

CDKN2A (p16)

A 4-year-old girl with a history of acute myeloid leukemia is referred to genetics by her pediatrician to rule out NF1. During the physical exam, you note that the child has several café-au-lait spots and some hypopigmented macules. In assessing the family, there are no skin findings or cancer in the mother's side. The father is not in the picture, and no information is known about his family. Genetic testing is negative for NF1, but you order additional testing for a cancer predisposition syndrome that mimics NF1, called?

CMMRD

Ms. Pierre presents to the clinic with recent diagnosis of fibrocystic breast disease. Upon further evaluation of her medical record, she has a personal history of uterine fibroids and hypertension. Ms. Pierre's family history includes the following: Brother with intellectual disability Father diagnosed with colon cancer Mother no cancer reported, but underwent a hysterectomy at age 54 due to abnormal vaginal bleeding Maternal aunt diagnosed with endometrial cancer Maternal uncle with trichilemmomas Maternal grandmother diagnosed with a multinodular goiter Ms. Pierre should be evaluated for what syndrome

COwden syndrome

Dilated cardiomyopathy

Cardiac dilation and reduced systolic function Does not always cause symptoms but can be life threatening for some Fatigue, shortness of breath, reduced ability to exercise, swelling in legs, ankles, feet, abdomen, and chest pain causes : myocarditis coronary artery disease, metabolic disorders, toxins, diabetes, some cancer medications Most common in men ages 20-50 but can affect people of all ages Incidence of idiopathic DCM 35-40/100,000; 25% are familial Nearly always AD with very variable expression

Alpha-1-Antitrypsin Disorder

Causes lung and liver disease w/ variable expressivity; age onset 20-50 Shortness of breath and wheezing; recurring respiratory infectionsFatigue COPD including emphysema or chronic bronchitis Liver disease in 10% infants, leading to jaundice15% of adults develop cirrhosis Hepatocellular carcinoma Panniculitis - painful bumps or nodules under the skin AR with incidence 1/1500Treatment and management involves prevention and monitoring, avoidance of smoking and alcohol Lunch and or liver transplant may be indicated

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Characterized by numerous cysts in the kidneys Most common inherited kidney disorder Symptoms usually appear 30-40, but can even in childhood Common symptoms: pain in the back and the sides, headaches, liver and pancreatic cysts, urinary tract infections, abnormal heart valves, urinary tract infections, high blood pressure, kidney stones, blood in urine, brain aneurysms, diverticulosis Pain can be temporary or persistent, mild or severe About 90% are inherited in AD fashion by PKD1 and PKD2 mutations Additional mutation may make cysts grow faster and increase rate of disease Other 10% are new mutations; homozygous cases may make cysts grow faster and increase No cure but treatments can prolong life

What are two types of genetic change that can activate a proto-oncogene? Chromosome translocations Gene silencing Whole gene deletion Point mutations

Chromosomal translocation point mutation

CHARGE syndrome

Coloboma Heart defects Atresia of the choanae Renal anomalies Growth impairment Ear abnormalities/deafness

Lynch syndrome

Colon, endometrial (uterine), gastric (stomach), ovarian, hepatobiliary (liver/gallbladder), small bowel, urinary tract, brain, pancreatic, and prostate cancers, and rare skin tumors called sebaceous neoplasms; due to pathogenic variants in MLH1, MSH2, MSH6, or PMS2 or deletions of EPCAM

Stickler's Syndrome

Connective tissue disorder, related with Marshall syndrome AD inheritance in majority (some AR inheritance)Affects alpha1-chain of type II collagen (COL2A1 gene on Ch12). If COL11A1 on Ch1, called Marshall's syndrome Feats: - orofacial dysmorphism (flat midface, depressed nasal bridge, short nose with anteverted nares, Pierre Robin sequence) - ophthalmologic abNs (AbN architecture of the vitreous gel, high myopia, frequently retinal detachment) - joints (hypermobile and secondary OA) - sensorineural deafness - mitral valve prolapse

PHACES Syndrome

Constellation of congenital malformations, all associated with large, segmental facial haemangioma FACE)Suggested cause is some insult between 3-12 weeks gestation Clinical feats: - Posterior fossa malformation, esp Dandy-Walker (absent/hypoplastic cerebellar vermis + markedly dilated 4th ventricle) - Haemangiomas - Arterial anomalies,esp cerebrovascular --> Stroke and neuro complications - Cardiac defects, esp CoA, PAPVR, tricuspid atresia + aortic atresia, PDA, VSD - Eye AbNs incl optic nerve atrophy, colobomas, exophthalmous + congenital cataracts - Sternal cleft or supraumbilical raphe

A family presents for a cancer risk assessment after their youngest daughter was diagnosed with lymphoma at 13 months, and subsequently passed away at 18 months. The couple has a son, age 7, diagnosed with leukemia at age 6, who was noticed to have multiple café au lait spots. They also have an unaffected daughter age 5. Dara, the mother, is 30-years-old and has no personal history of cancer. She has had a few colonoscopies due to bowel issues, and was found to have a total of 3 adenomas. She has one brother, age 32, with no history of cancer, and he has no children. Dara's mother is 53-years-old, and was diagnosed with breast cancer at age 51. She underwent a TAH/BSO in her 30s for uterine fibroids. Dara's father was recently diagnosed with colon cancer at 57-years-old. Peter, the father, is 31 years old and has no personal history of cancer. He has two sisters, ages 29 and 33, both with no history of cancer. Peter has 4 nieces/nephews with no cancer history. His mother is 52-years-old and his father is 55-years-old. His father underwent a colonoscopy recently, and was identified to have 2 adenomas, which were removed. Peter's paternal grandfather was diagnosed with colon cancer at age 68, and passed away a few years later in his 70s. What hereditary cancer syndrome are you concerned about for this family?

Constitutional Mismatch Repair Deficiency (CMMRD) syndrome

NCBI what is it?

Curates all known genetic sequences, as well as other genetic research related information.

what lesion is common in hereditary leiomyomatosis and renal cell cancer

Cutaneous leiomyomas

A 27-year-old woman who is 9 weeks pregnant has a nephew with Down syndrome. The woman is concerned about the recurrence risk to her fetus. Which of the following is the best first step in counseling this woman about her risk? A .Karyotype her to determine whether she has a translocation B. Offer her prenatal diagnosis C. Recommend she have serum screening and fetal ultrasound D. Request a copy of the nephew's karyotype

A young woman of northern European descent is the single parent of a child with autosomal recessive cystic fibrosis (CF). She marries a genetically unrelated man of northern European descent and wishes to have more children. What is the risk that he is a carrier of CF? Assume the frequency of CF is 1/2500 in this population A, 1/2500 B. 1/1250 C. 1/50 D. 1/25 E.1/4

Hormone therapy is commonly used for which two cancers? A. Leukemia and lymphoma B. Thyroid and kidney C. Colon and pancreatic D. Breast and prostate

Hunter syndrome is a rare mucopolysaccharoidosis with X-linked recessive inheritance. A woman with two affected brothers is referred for genetic counseling. Which of the following is correct? A. The probability that she is a carrier is 2 in 3 B. If she is a carrier, then the probability that each of her sons will be affected is 1 in 4 C. If she is a carrier, then the probability that each of her daughters will be a carrier is 1 in 4 D. Before any carrier testing is carried out, the woman can be correctly informed that the probability that her first son will be affected is 1 in 4

In the United States, ornithine transcarbamylase (OTC) deficiency has an incidence of 1/40,000. What is the allele frequency for OTC deficiency in the United States? A.1/200 B. 1/400 C. 1/20,000 D. 1/40,000 E. 1/160,000

Kai is a 9-year-old male who presented with shortness of breath and a general feeling of fatigue over the last 4-6 months. His pediatrician ordered a CBC, which was concerning. Kai then had a bone marrow evaluation that demonstrated dysplastic changes in all three cell lines, deemed to be consistent with myelodysplastic syndrome (MDS). Should he be referred for genetic counseling to discuss the option of germline testing? A. No, because leukemias are the most common type of pediatric cancer B. No, the family history should first be ascertained C. Yes, he should be referred once his MDS progresses to leukemia D. Yes, this type of cancer can be associated with germline predisposition in children and young adults E. No, MDS is always sporadic in nature

What pathological findings are more typically associated with a BRCA1 mutation? A. ER +, PR +, Her2 + B. ER +, PR -, Her2 + C. ER -, PR-, Her2 + D. ER-, PR-, Her2 -

Which is NOT a helpful technique or consideration when counseling/educating adults? A. Approach the client as a partner in the learning process B. Permit the client to help dictate the direction of learning C. Build upon the client's prior knowledge D. Prepare an agenda before meeting with the client, and do not deviate from it.

Which of the following is NOT a disorder of organic acid metabolism? A. propionic acidemia B. multiple carboxylase deficiency C. methylmalonic acidemia D. galactosemia

Which of the following is NOT a reason to stage cancer? A. Make treatment decisions B. Determine which clinical trials are most appropriate C. Give prognostic information D. To determine eligibility for financial assistance for cancer treatment

Which of the following is NOT an appropriate strategy for crisis intervention? A. Ask your patient how they have coped with difficult situations in the past and explore whether the same strategies many be helpful B. Ask your patient to describe their available social support and help them to determine who or what will be most helpful to seek out first. C. During your discussion, assess for any suicidal ort homicidal thoughts or plans D. Help your patient to put their situation in perspective by telling that they "will be OK" or "it's not as bad as you think"

Which of the following is an issue to consider when providing counseling for pre-symptomatic testing in an adult? A. Current emotional well-being B. Coping strategies C. What will be done with a positive or negative results D. Current emotional well-being, Coping strategies, and What will be done with a positive or negative results

You have a client who loves to hear herself talk. You have even seen her talking to herself in the waiting room when there is no one around. If you want to shut off the verbose behavior of your client, you might consider using: A. Yawns b. Silence C. Open-ended questions D. Close-ended questions

You will be presenting a grand rounds talk entitled, "Principles of Pharmacogenomics." Which of the following statements is NOT accurate information to provide in the talk? A. Pharmacogenomics is used to provide "personalized medicine." B. Pharmacogenomics is the study of the genetic causes of the variability in drug response. C. Pharmacogenomics is used to evaluate the potential for drug benefit as well as toxicity in an individual. D. Pharmacogenomic testing can guarantee a medication will work for the individual.

Your patient is a 49-year-old woman recently diagnosed with colon cancer. Her family history is significant for a sister with endometrial cancer at 45 years and a father with colon cancer at 63 years. Immunohistochemical staining for MLH1, MSH2, MSH6, and PMS2 proteins in your patient's tumor showed positive expression of the MLH1 and PMS2 protein products, but lack of expression of the MSH2 and MSH6 protein product. Which of the following statements is FALSE? A. Based on this result, it is likely that this tumor would also be MSI-H B. This family fulfills the revised Amsterdam criteria C. The most likely cause of the cancer in the family is a pathogenic variant in MSH2 D. If genetic testing for MLH1, MSH2, MSH6, and PMS2 is completed, and no mutation is found, this will rule out Lynch syndrome E. The risk for endometrial and ovarian cancer and the option of a hysterectomy/oophorectomy should be discussed with this patient

A 25-year-old woman has mild expression of hemophilia A. A genetic diagnosis reveals that she is a heterozygous carrier of a mutation in the X-linked F8 gene. Which of the following is the most likely explanation for mild expression of disease in this individual? A. Her father is affected and her mother is a heterozygous carrier B. X inactivation does not affect the entire chromosome C. One of her X chromosomes carries the SRY gene D. A high proportion of the X chromosome carrying the mutation are active E. A nonsense mutation is causing formation of a truncated protein

A 28-year-old woman gives birth to an infant who is small for gestational age after a difficult pregnancy complicated by oligohydramnios. The infant is placed in the NICU and tissue from the umbilical cord is sent for cytogenetic analysis. The infants karyotype is 46,XY with no apparent abnormalities. No biochemical abnormalities are detected. The observed IUGR might have been caused by: A. Chromosomal deletion B. Expansion of tandem nucleotide repeats C. Fetal trisomy D. Confined placental mosaicism E. Genomic imprinting

A child with a cleft palate, heart defect, and extra fifth fingers is found to have 46 chromosomes with extra material on one homologue of chromosome 5. This chromosome abnormality is best described by which of the following terms? A. Polyploidy B. Balanced rearrangement C. Ring formation D. Unbalanced rearrangement E. Mosaicism

A couple has a son with a multifactorial disorder in which it is more common for females to be affected. Which of the following statements about recurrence risk is true? A. Recurrence is lower for a next child than if a daughter had been affected, and would be higher for a son than a daughter B. Recurrence is lower for a next child than if a daughter had been affected, and would be higher for a daughter than a son C. Recurrence is higher for a next child than if a daughter had been affected, and would be higher for a son than a daughter D. Recurrence is higher for a next child than if a daughter had been affected, and would be higher for a daughter than a son

A patient with Prader-Willi syndrome does not have a 15q deletion but inherited both copies of chromosome 15 from his mother. A. Allelic heterogeneity B. Locus heterogeneity C. Ascertainment bias D. Uniparental disomy E. Anticipation

Which of the following is NOT true about CRC? A. The highest risk age group is those between 65 and 74 B. Among all races, the incidence for men is higher than for women C. While the incidence of CRC has decreased in those over age 50 over the past generation, it is increasing among younger individuals D. The death rate for black individuals is lower than that of white and Asian individuals

Which of the following is true? A. Prader-Willi syndrome can be caused by deletions in maternal chromosome 15q11-q13 B. Imprinting is not involved in hydatidiform molar pregnancies C. Genetically imprinted loci are only located on chromosome 15 D.Some genes may be expressed differently when inherited from one sex versus the other

A pediatrician refers a 2-week-old baby named Aoife for a genetic workup. Aoife is very tiny, with café-au-lait spots and hypoplastic thumbs. Based on the clinical findings, you suspect she may have Fanconi anemia (FA) and recommend chromosome breakage testing, which comes back positive. You discuss genetic testing, but her parents are hesitant and don't understand the recommendation for it since the diagnosis has been made. How would you counsel them? A. The chromosome breakage result may represent a false positive. Genetic testing is needed to properly confirm the diagnosis B. Aoife likely represents a de novo mutation, but it is important to identify her genetic status to inform health management options in relatives. Once her mutation status is known, parents should be tested C. Aoife likely inherited a mutation from each of her parents and some of the Fanconi genes are associated with increased cancer risk in carriers D. Aoife likely inherited her mutation from either her mother or her father. Identifying her genetic status would allow for cascade testing in either maternal or paternal relatives E. It is important to know which Fanconi genes are involved to accurately determine whether Aoife is at risk to develop MDS, leukemia or a squamous cell carcinoma (SCC)

A young woman delivers a baby, and fairly soon after develops some new neurological symptoms. It is suspected that she might have post-partum depression, but she then has a seizure, becomes comatose, and has some brain swelling. A CT scan of the brain is normal. Which of the following would NOT help you in trying to diagnose and treat her? A. hemodialysis B. lactulose therapy C. EEG D. echocardiogram E. ammonia level measurement

Aarskog syndrome is one of the most clinically distinctive phenotypes among hereditary syndromes due to all of the following EXCEPT: A. Children with Aarskog exhibit distinct facial, skeletal and genital features B. One of its classical features is a "shawl" scrotum C. While it is X-linked, many carrier females exhibit subtle findings D. Affected children tend to be tall, with a sunken chest and inguinal hernia

An African American couple comes for prenatal genetic counseling for a family history of sickle cell anemia. The wife's two siblings have sickle cell anemia, and the husband's paternal uncle was also affected. The couple has not had carrier testing. The incidence of sickle cell anemia in their population is 1 in 400. What is their chance of having a child with sickle cell anemia? A ¼ B ⅛ C.1/12 D. 1/18 E. 1/32

High rates of DNA hypermethylation in CpG promoters were first described in 1999. This hypermethylation: A. Occurs primarily in hereditary cases of CRC B. Is reported as a range, rather than low or high C. Is only associated with CRC D. Is present in approximately 30% of CRCs

In a family with mitochondrial disease, which of these individuals is least likely to be clinically affected? A. The son of an affected female B. The daughter of an affected female C. The son of a woman's whose mother is affected D. The daughter of a man's whose mother is affected E. The daughter of a woman's whose mother is affected

In humans, which of the following repair mechanisms would most likely repair damage caused by ultraviolet radiation? A. Recombination repair B. Base excision repair C. Photoreactivation of pyrimidine dimers D. Nucleotide excision repair E. Mismatch repair

Molecular analysis of the ornithine transcarbamylase (OTC) gene is carried out on two unrelated boys with X-linked OTC deficiency. One is found to have a large deletion in the 5' end of the gene; the other has a missense mutation in an exon toward the 3' end of the gene. Choose one of the following terms that best matches this clinical vignette. A. Variable expressivity B. Anticipation C. Incomplete penetrance D. Allelic heterogeneity E. Locus heterogeneity

Of the following genes that regulate chromosomal instability in CRC, which one is NOT related to DNA damage response? A. MER11 B. ATM C. TP53 D. APC

Phenylketonuria shows an autosomal recessive inheritance pattern with an incidence of 1 in 10,000. Assuming that a population is in Hardy-Weinberg equilibrium, which of the following is correct? A. The frequency of the mutant allele is 1 in 1,000 B. The frequency of the normal allele is 49 in 50 C. The carrier frequency is 1 in 100 D. The carrier frequency is approximately 1 in 50

The Philadelphia chromosome is associated with which type of cancer? A. Melanoma B. Pheochromocytoma C. Gastric cancer D. Chronic myelogenous leukemia

Triploidy is the result of three copies of each human chromosome and is one of the most common causes of spontaneous miscarriage. Which of the following occurrences is the most common mechanism by which triploidy arises? A. tetraploid conception with loss of one copy of each chromosome B. chimerism C. two eggs fertilized by one sperm D. one egg fertilized by two sperm

Trisomy 16 is characterized by which of the following clinical scenarios? a: Rarely survives to 3 years of age b: Multisystem failure within a year of birth c: Cardiac arrest within 3 days of birth d: No live births

When you are evaluating a patient for a possible polyposis syndrome, all of the following pieces of information are necessary to provide an accurate risk assessment EXCEPT: A. Number of polyps B. Pathology of the polyps C. Age at polyp diagnosis D. How the polyps were found

Which is NOT true about how association studies work? A. They look for SNPs or variants in disease vs control population B. The studies are done on populations C. They test for thousands of SNPs at the same time D. They do not require a stringent statistical threshold

Which of the following explains why PGx is so important for oncology therapies? A. Genetic mutations often must be determined to decide if a target for a therapy exists B. Oncology therapies often have narrow therapeutic indices C. Oncology therapies target DNA D. Both A and B are correct

Which of the following statement is NOT true about DiGeorge syndrome? A. The triad of features best known in association with this syndrome includes hypocalcemia, immunodeficiency and congenital heart disease B. Sometimes the only indication on prenatal ultrasound for DiGeorge is polyhydramnios C. The genetic mechanism of a de novo deletion causing DiGeorge is non-allelic homologous recombination D. It is caused by a continuous gene deletion at 17p

Which of the following statements about Hereditary Diffuse Gastric Cancer is CORRECT? A. HDGC is associated with an increased risk for diffuse gastric cancer and ductal breast cancer B. There are many effective surveillance options that are available for early detection of diffuse gastric cancer D. CDH1 mutation testing only identifies mutations in 30-50% of families that meet criteria E. Only a small proportion of individuals who undergo total gastrectomy are found to have foci of diffuse gastric on pathology

Which of the following statements regarding Knudson's Two-Hit Hypothesis is true? A It has been thoroughly debunked by the scientific community. B. It explains hereditary, but not sporadic, retinoblastoma. C. This theory holds true for most types of cancer in that they only require two hits to become metastatic. D. It represented the first time that carcinogenesis was described as a process rather than a single event.

Which of the following statements regarding the term "prevalence" is FALSE? A. It measures new and old cases B. An increased prevalence reflects a decreased rate of mortality C. Combines both measures of incidence and likelihood of surviving cancer D. It is unrelated to incidence

Your team diagnoses an atrial septal defect, bilateral hydronephrosis, and clubfeet in a newborn female. Cytogenetic analysis reveals an unbalanced translocation between the short arm of chromosome 2 and the long arm of chromosome 8 designated as - 46, XX, der (2), t(2;8) (p24; 924), resulting in a loss of genetic material from the top of chromosome 2 and a duplication of genetic material from the bottom of chromosome 8. The newborn has three healthy siblings, and the family history is negative for congenital anomalies or recurrent pregnancy losses. The parents ask about the risks for having another child with this condition. Of the following, you are MOST likely to advise them that the risks for recurrence: A. Are probably between 20% and 30% because of a higher risk for miscarriage in fetuses who have unbalanced translocations B. Are negligible since the parents and sibs are healthy and there is no history of recurrent miscarriages C. Are as high as 50% because most unbalanced translocations are passed down from a balanced translocation carrier D. Cannot be determined unless chromosome studies are performed on both parents

he "triplet repeat" in Huntington Disease refers to: A. An amino acid repeat consisting of: Gly-X-Y B. A nucleic acid repeat consisting of: G-A-T C. An amino acid repeat consisting of: C-A-G D. A nucleic acid repeat consisting of: C-A-G E. A nucleic acid repeat consisting of: T-A-G

Personal values are more important than cultural values in understanding differences in resistance among ethnic groups. True or False?

False

A couple have a severely affected son with Hunter syndrome, which is diagnosed by assaying iduronate sulfatase. Two years later, they have a daughter with the same severe condition and confirmed by enzyme assay. What would be the most important next step in evaluating this family? A. Enzymatic carrier testing for both of the parents B. Determine paternity by HLA typing of the father C. Take a careful pregnancy history to check for teratogenic exposures D. Karyotype the daughter E. Karyotype the parents

D. Karyotype the daughter(note: Hunter syndrome is X-linked recessive)

The condition that exists when an organism gains or loses one or more chromosomes but not a complete haploid set is known as ________. A. polyploidy B. eupoidy C. triploidy D. trisomy E. aneuploidy

Parents of a newborn child with trisomy 21 and a 47,XX,+21 karyotype are interested in knowing the origin of their daughter's trisomy. A polymorphic marker is studied that maps to the proximal long arm of chromosome 21 in this family. The mother has alleles 1 and 2, the father has alleles 1 and 3, and the child has 2 copies of allele 1 and a single copy of allele 3. Which of the following interpretations about when the nondisjunctional even occurred is correct? A. The trisomy resulted from a paternal meiosis II nondisjunction B. The trisomy resulted from a maternal meiosis II nondisjunction C. The trisomy result from a paternal meiosis I nondisjunction D. The trisomy resulted from either a maternal meiosis II or paternal meiosis I nondisjunction E. The trisomy resulted from either a maternal meiosis I or paternal meiosis II nondisjunction

D. The trisomy resulted from either a maternal meiosis II or paternal meiosis I nondisjunction

deletion 1q 21.1

DD, short, cataracts, bone abnormalites, hearing loss, heart defects

McCune-Albright syndrome

Defect: - Mosaicism - Mutation affecting *G-Protein Signaling* Symptoms: - *Unilateral Café-au-Lait Spots* - *Polyostotic Fibrous Dysplasia* - *Endocrinopathy* - Lethal if Mutation occurs Before Fertilization (Affecting all Cells), but Survivable in patients with Mosaicism

Willams Syndrome

Deletion of 7q11 - usually confirmed by microarray or FISH - loss of gene for elastin -Hypocalcemia in childhood -Supravalvular aortic stenosis -Peripheral pulmonary artery stenosis -Short stature -Full lower lip -Sloping shoulders -Outgoing in childhood which can change dramatically into adulthood -Intellectual impairment -1 in 7,500 to 10,000 people

deletion 17q 21.31

Developmental delay and ID Hypotonia and low birth weight Characteristic facial features including high forehead, tubular/pear shaped nose, large ears Friendly nature Heart defects Kidney anomalies Epilepsy

allelic heterogeneity

Different mutations in the same locus produce the same phenotype

A 2-year old girl is diagnosed with pleuropulmonary blastoma. Her grandmother had papillary thyroid cancer, but otherwise there is no other family history of cancer. A referral to genetics is warranted due to the association between this type of pediatric tumor and a mutation in what gene? A. PTCH1 B. RET C. TERT D. TP53 E. DICER1

The above MSI-high features were identified in a 65-year-old patient with colon cancer who was adopted and has no information about his birth family. There was a loss of MLH1 and PMS2 on immunohistochemistry (IHC). What would be the next best step(s)? A. Go straight to ordering MLH1 genetic testing B. Go straight to ordering PMS2 genetic testing C. You Answered Order MLH1 methylation studies → if methylated, order MLH1 genetic testing D. Order MLH1 methylation studies → if not methylated, no further testing E. Order MLH1 methylation studies → if not methylated, order MLH1 genetic testing

What are some factors that should be taken into consideration regarding preventative colectomy in an individual with FAP? A. Symptoms B. Number and location of polyps C. Risk for colorectal cancer in the near future D. Compliance with continued surveillance E. All of these factors should be taken into consideration

Which of the following statements about retinoblastoma is NOT true? A. Bilateral disease is diagnostic of heritable retinoblastoma, regardless of the RB1 test result B. Germline RB1 mutations are associated with an increased risk to develop an osteosarcoma C. Approximately 15% of children with unilateral disease have a germline RB1 mutation D. Individuals with hereditary retinoblastoma are at elevated risk for ocular and non-ocular cancers E. Disease penetrance is approximately 60% in mutation carriers

A 23-year-old woman has a baby with the karyotype 47,XY,+21. Which of the following is the correct conclusion? A. This woman's risk for having another baby with a chromosome abnormality is the same as other women her age B. Either the woman or her husband probably has a Robertsonian translocation C. Either the woman or her husband probably has germ line mosaicism D. Either the woman or her husband probably carriers a balanced reciprocal translocation E. Both members of the couple probably have normal chromosomes

A man and a woman, each of whom has autosomal recessive congenital deafness, have four biological children, each of whom has normal hearing. Choose one of the following terms that best matches this clinical vignette. A. Variable expressivity B. Anticipation C. Incomplete penetrance D. Allelic heterogeneity E. Locus heterogeneity

A phenotypically normal woman with a 45, XX, -14, -21, +t(14q, 21q) karyotype has a karyotypically normal husband. Among their liveborn offspring, which of the following is Least likely? A. 45, XY, -14, -21, +t(14q,21q) B. 46,XY, -21, t(14q,21q) C. 5, XX, -14, -21, +t(14q,21q) D. 46,XX E. 46,XY, -14, +t(14q,21q)

Although the most frequent forms of Down syndrome are caused by a random error, nondisjunction of chromosome 21, Down syndrome occasionally runs in families. The cause of this form of familial Down syndrome is ________. A. too many X chromosomes B. a chromosomal aberration involving chromosome 1 C. an inversion involving chromosome 21 D. a maternal age effect E. a translocation between chromosome 21 and a member of the D chromosome group

Chromosome analysis of a child with multiple birth defects reveals the following karyotype: 46,XY,der(8),t(8;12)(q22;p12). Which of the following interpretations is false? A. Both parents should be offered chromosome analysis B. The child has partial monosomy 8q and partial trisomy 12p C. The parents should be offered prenatal diagnosis in future pregnancies D. The phenotypically normal siblings of this child may have a balanced translocation E. Meiotic nondisjunction was the cause of this chromosome abnormality

Chromosome analysis of a child with multiple birth defects reveals the following karyotype: 46,XY,der(8),t(8;12)(q22;p12). Which of the following interpretations is false? A. The child has partial monosomy 8q and partial trisomy 12p B. The parents should be offered prenatal diagnosis in future pregnancies C. The phenotypically normal siblings of this child may have a balanced translocation D. Both parents should be offered chromosome analysis E. Meiotic nondisjunction was the cause of this chromosome abnormality

Predispositional testing is: A. Testing for a condition with complete penetrance prior to the development of symptoms B. Testing for a condition in which a person is showing symptoms C. Testing for a condition to determine when a disease will occur D. Testing for a mutation that is not inherited, but occurs sporadically during a person's lifetime E. Testing for a mutation that increases the risk of a specific disease based on family history

The genes causing myotonic dystrophy and fragile X syndrome change as they are passed from generation to generation, causing an increase in severity of phenotypic manifestations because of expansion in the size of regions composed of trinucleotide repeats. A. Allelic heterogeneity B. Locus heterogeneity C. Ascertainment bias D. Uniparental disomy E. Anticipation

Which of the following is not true about mtDNA? A. It contains no introns B. The rate of mutations is 10 times higher than that of nuclear DNA C. It contains 2 rRNAs and 22 tRNAs D. Variable expression in mitochondrial diseases is due to mtDNA heteroplasmy E. It has many DNA repair mechanisms

Which of the following statements about congenital malformations is false? A. Some are isolated with no other concurrent findings B. Some may represent part of an identifiable syndrome C. Some are isolated and may have increased recurrence risks D. Congenital malformations that will require medical attention by the age of 5 are not rare events, and may have a frequency of 5% in all newborns E. As the number of minor anomalies noted upon physical examination increases, the chance that the individual also has a major malformation decreases

A full-length cDNA clone will contain sequences corresponding to each of the following except: A. Translation start codon B. Exons C. Poly-A tail D. 5' untranslated region E. Introns

E.introns

A 40-year old woman with Li-Fraumeni syndrome comes for genetic counseling after testing confirms she has a p53 pathogenic variant. Her symptomatic 18-year old son also has the pathogenic variant. The mother repeatedly suggests that gene therapy should be available soon to repair the gene for her son and perhaps his test should be repeated in case there was a mix-up at the laboratory. The mother is exhibiting which of the following coping styles?

Escape-avoidance

Aarskog syndrome

FGD1, Rho, Xp11.22 hypertelorism, shawl scrotum, brachydactyl, ID, vertebral abnl FGD1 seq

Hereditary Leiomyomatosis and RCC Syndrome

FH gene AD development of multiple leiomyomas (smooth muscle tumors) in the skin and uterus (fibroids) as well as an aggressive form of kidney cancercutaneous leiomyomas on the trunk arms and legs

PGRN what is it

Facilitates research in the area of PGx.

Using programmed learning to develop helping skills reduces the need for practice of new skills. True or false?

False

What skin lesion is common in BHD

Fibrofolliculoma

A 36-year-old male with moderate developmental delay, large ears and hands is very shy and awkward in social situations and starts rocking and flapping his hands when he is upset. Which of the following is most likely his diagnosis? A. Fragile X syndrome B. Down syndrome C. Hurler syndrome D. Rett syndrome E. Williams syndrome

Fragile X

Osteogenesis imperfecta

Genes: COL1A1 (ch17; more severe pheno w/mutn b/c there are 2 alpha strands vs. 1 beta strand), COL1A2 (ch7), form protein triple helixType I -- AD, mild, blue sclera, brittle bones, no deformitycollagen: normal quality, AMOUNT is reducedType II: AD, neonatal lethal, abnormal collagenType III: AD, progressive deforming, fractures at birth, small, blue scleraType IV: AD, normal sclera, mild/mod bone deformity, short stature, fractures

Trisomy 21 (Down Syndrome)

Genetic disorder resulting from the presence of 3 #21 chromosomes; characterized by heart and respiratory defects and varying degrees of metal retardation

Medulloblastoma occurs at highest frequency in

Gorlin syndrome/nevoid basal cell carcinoma syndrome

Hereditary diffuse gastric cancer syndrome

HDGC High risk for diffuse type gastric cancer (cells multiply in stomach lining) and lobular type breast cancer Prostate cancer and colon cancer can also occur

Hypertrophic cardiomyopathy

Heart muscle becomes abnormally thick Genetically heterogeneous majority AD Shortness of breath, chest pain, and life threatening arrhythmias Mutation rate detection from gene panel tests is about 60% when disease is clearly familial - two inherited forms are Fabray disease and Noonan syndrome

Cdh1

Hereditary diffuse gastric cancer

Renal Tubular disorders

Heterogenous group of rare hereditary and acquired diseases Dysfunctions of transporters and channels in the renal tubular system Fluid loss and abnormalities in electrolyte and acid base homeostasis, salt homeostasis, water balance, etc Suspected when characteristic clinical features and/or laboratory finding are present; diagnosis confirmed by genetic testing Treatment options vary

The BRCAPRO model incorporates which of the following cancers when calculating the chance that an individual has a BRCA1 or BRCA2 mutation? I. Female Breast II. Pancreas III. Ovarian IV. Prostate V. Male breast

I,II,V

Mucopolysaccharidoses

IEM, enzyme deficiency, urine GAGs highHurler, Scheie = AR, alpha-L-iduronidaseHunter = XL, iduronidase sulfatase

Catecholaminergic polymorphic ventricular tachycardia

Impaired calcium regulation Abnormal fast/irregular heartbeat Lightheadedness, dizziness, fainting, cardiac arrest, sudden death Prevalence 1/10,000Mutations in the RYR2 gene: AD but half are de novo Mutations in CASQ2 gene: AR

Brugada syndrome

Increased risk of abnormal ventricular heart rhythms - potentially life threatening Some people asymptomatic Much more common in men, more frequently in Asians Treatable with preventive measures (avoiding aggravating medicines, reducing fever, implantable cardioverter-defibrillator)Dizziness, syncope, labored breathing, irregular heartbeats or palpitations, and sudden cardiac arrest Inherited form is autosomal dominant Not much known about genetics but 20-30% caused by SCN5A mutation

Prader-Willi Syndrome (PWS)

Inherited from the father; characterized by reduced motor function, obesity, mental deficiencies; resultes form lack of expression of a singel gene SNRNP which encodes a small nuclear ribonuceloprotein which is a complex that controls gene splicing. Offspring does not carry active copy of PW gene. (del(15)(q11.13)

FISH analysis

Involves using a fluorescent DNA probe; probes are specific to telomeric DNA

Alport syndrome

Kidney disease and progressive loss of kidney function, resulting in end stage renal disease Hematuria (blood in urine), proteinuria (protein in urine), sensorineural hearing loss during late childhood or early adolescence (caused by abnormalities in the inner ear)Anterior lenticonus (misshapen lenses) and abnormal coloration of the retina Pathognomonic for Alport - if you have lenticonus, you almost definitely have alport Incidence 1/50,000About 80% of cases are caused by mutations in the COL4A5 gene (X-linked). Carrier females usually only have hematuria, some females have more severe symptoms Approximately 15% have autosomal recessive mutations in COL4A3 or COL4A4; some are unaffected, some have milder condition called thin basement membrane (characterized by hematuria)About 5% are autosomal dominant (less severe)

RASopathies

Largest known group of malformation syndromes caused by germline mutations of Ras/MAPK pathway -Neurofibromatosis -Legious -Noonan -Costello -Cardio-facio-cutaneous -Capillary malformation-arteriovenous malformation

Inherited Cardiac Conditions Examples

Long QT syndrome, Brugada syndrome, catecholamingeric polymorphic ventricular tachycardia, Hypertrophic cardiomyopathy, Dilated cardiomyopathy

Multiple endocrine neoplasia, type 1

MEN1 Parathyroid gand, pancreatic cancer, pituitary gland cancer. Other endocrine cancers seen include adrenal cortical tumors, neuroendocrine tumors and rarely pheochromocytomas Majority of tumors are benign

Multiple Endocrine Neoplasia Type 1

MEN1, menin, AD parathyroid tumor, angiofibroma, cafe au lait, pituitary MEN1 sequencing, tumor suppressor

Hereditary Papillary RCC Syndrome

MET increases the risk of papillary type of renal cell carcinoma (type 1 papillary renal cell cancer)

Lynch syndrome

MLH1, MSH2, MSH6, PMS2, or EPCAMADColon, rectum and endometrial cancer most commonstomach, small intestine, liver, gallbladder ducts, urinary tract, brain, and skin can also occur

Trisomy 18 (Edwards Syndrome)

MR Rocker bottom feet Prominent occiput Clenched fists w/overlapping fingers Congenital heart disease Horseshoe kidneys IUGR/FTT 90% die by age 1

Mutations in which MMR gene are overrepresented in the endometrial cancer population?

MSH6

Neurocutaneous disorders Examples

Neurofibromatosis type 1 (NF) Neurofibromatosis type 2 Tuberous sclerosis complex

Micro-duplication 16p11.2

Mild developmental delay and language delay Seizures Mental health problems Minor facial dysmorphism Underweight Small head circumferences

CHEK2

Moderate risk gene 2 fold increase breast cancer increased risk for colon and ovarian suggested

Autosomal Recessive Polycystic Kidney Disease (ARPKD)

More rare and more severe - Cysts in the kidneys that lead to kidney failure Congenital hepatic fibrosis (liver scarring) is universal and hepatobiliary disease is very common Problems in blood vessels in brain and heart Other associated features: depressed nasal bridge, macrotia (enlarged ear), hypoplasia of ear cartilage, low set and posteriorly rotated ears Severity varies; signs frequently begin before birth and can lead to kidney failure before adulthood - often called infantile PKD Babies with the worst cases die hours or days after birth due to respiratory difficulties or respiratory failurePKHD1 gene; autosomal recessive Carriers typically do not show symptoms - diagnosis is typically done through ultrasound when there are large echogenic kidneys and hepatobiliary involvement - oligohydramnios may occur and result in pulmonary hyper plasiaI f child survives long enough through renal disease you may see other long term issues such as portal hypertension and hepatosplenomegaly

Friedreich Ataxia (FDRA)

Most common AR ataxialate childhood/early adulthood onset absent lower limb reflexes loss of position and vibration sense, hypertrophic cardiomyopathy, diabetes, dysarthria, dysphagia, scoliosis, optic nerve atrophy Triplet repeat of FXN gene - GAA, over 100 repeats, no anticipation

Marfan syndrome

Mutation in FBN1 gene (15q21) affecting fibrillin 1 protein Increase in transforming growth factor beta or TGF - beta Affects heart, blood vessels, bones, joints, eyes, lungs, skin, and nervous system Joint laxity reduced lower to upper segment body ratio, protruding or sunken chest, long fingers that can sometimes bend back toward the wrist Dislocation of the lens of the eye Aortic enlargement and dissection can be life threatening Incidence 1/500075% inherited/25% de novo - AD Nearly half people with Marfan do not know they have it - anyone tall with long limbs and fingers is suggested of having the syndrome

Beal syndrome - Congenital contractural arachnodactyly (CCA)

Mutation in a gene FBN2 that codes for fibrillin 2 protein, 5q23Similar to marfan syndrome but eyes are unaffected and joints are affected differently Inability to fully extend fingers, elbows, toes and hips - muscles become tight and short and can restrict movement Long, slender fingers and toes, Scoliosis, pectus excavatum or carinatum, Reduced bone mass, Unusually small jaws, High arched palate Crumpled appearance to the top of the ear Aortic enlargement and/or mitral valve regurgitation

Locus heterogeneity

Mutations at different loci can produce a similar phenotype

Schwannomas are a characteristic finding in individuals with germline mutations in which genes?

NF1 and SMARCB1

PALB2

PALB2High breast, moderate ovarian, increased risk of pancreatic cancer

Sandra is a 49-year-old woman with no cancer history. She has three sisters and four brothers in their 30s-40s with no history of cancer. None of Sandra's nieces/nephews have cancer. Sandra's mother died at age 70 after a history of uterine cancer at age 66, and her father died at age 77 with no reported history of cancer. Sandra has three daughters, ages 27, 26, and 23. None of her daughters has a history of cancer. Her middle daughter had exploratory laparotomy for intussusception at age 9 years, and was found to have multiple colon polyps, but pathology is not available. Her youngest and oldest daughters have had no major medical conditions. Sandra's husband is a 53-year-old man with a history of renal cancer diagnosed at age 46, and a history of colon polyps. He has light pigmented marks on his buccal mucosa. He has two brothers in their 50s with no history of cancer, and two nieces and three nephews with no cancer. His mother was diagnosed with breast cancer in her 30s and passed away at age 72. His father was diagnosed with skin cancer at an unspecified age and passed away at age 77. What hereditary cancer syndrome are you concerned about for this family?

PJS

Betsy is a 45-year-old Ashkenazi Jewish female who was recently found to have 3 colonic adenomas on her first colonoscopy. She had a colonoscopy because of her 70-year-old father's diagnosis of rectal cancer at age 52 years. Her only paternal aunt died from ureteral carcinoma at age 62. This aunt had 3 sons; they are 38, 40 and 42 years old. Her 40-year-old cousin was recently found to have a sebaceous adenoma on his shoulder. Betsy's paternal grandmother died following childbirth at age 30 years, and grandfather died of a stroke at age 70 years. Which MMR mutation prediction model would account for Betsy's colonic adenomas?

PREMM model

Gorlin syndrome (aka: NBCCS)

PTCH Basal cell skin cancer and medulloblastomas Non-cancerous tumors are seen in the jaw, heart or ovaries

Noonan Syndrome

PTPN11, SOS1, KRAS, RAF1 (AD) facial features, renal malformation, bleeding disorders Sequencing in the above order webbed neck, pectus excavatum, short, pulmonary stenosis

Schwannomatosis

SMARCB1/INI diagnosis of exclusion with NF2 dermal and internal schwannomas no neurofibromas or acoustic neuromas Unilateral vestibular schwannoma, schwannomas, meningiomas; due to heterozygous variants in LZTR1 or SMARCB1

DICER1 tumor syndrome

Pleuropulmonary blastoma, thyroid cancer, and multinodular goiter; pediatric condition

Pseudoxanthoma elasticum (PXE)

Progressive disorder characterized by accumulation of calcium deposits and elastin fibers in the eyes, skin, blood vessels, and digestive track Yellowish bumps called papules on neck underarms and other skin areas of flexion (where joints bend) Abnormalities in eyes: peau d'orange or angioid streaks, bleeding and scarring of the retina, vision loss Mineralization of arteries causing arteriosclerosis or claudication (cramping and pain during exercise due to limited blood flow to the arms and legs)Incidence 1/50,000 worldwide; females diagnosed twice as frequently Mutation in ABCC6 gene, coding for MRP6 protein; AR with occasional pseudodominance

RMRP gene

RNA gene in nuclear genome (most are coded by mt genome)cartilage hair hypoplasiano protein product

Genitopatellar Syndrome

Rare condition characterized by: • Genital abnormalities, usually cryptorchidism and underdevelopment of the scrotum. • Missing or underdeveloped patellae, • Flexion contractures at the hips and knees including club feet • Intellectual disability, often severe including agenesis of the corpus callosum • Microcephaly • Hydronephrosis and/or multiple renal cysts • Other minor abnormalities affecting other parts of the body. • Autosomal dominant, all reported cases are de novo mutations• Mutation in the KAT6B gene which is located on the long arm of chromosome 10 (101q22.2) • KAT6B provides the information to make histone acetyltransferase which regulates the histones that attach to DNA and give the chromosomes their shape. • Important for early development including development of the skeleton and nervous system • The mode of action is still not understood how the mutation causes the disorder

Mutations in cancer susceptibility genes may not be accompanied by an external phenotype, as cancer syndromes are not always overtly syndromic. This may be either because they do not involve features aside from cancer predisposition, or because the variability of a syndrome can be extreme. Which of the following would be considered a cancer susceptibility syndrome that is OFTEN overtly syndromic?

Rasopathies

PTEN hamartoma tumor syndrome

Responsible gene: PTEN Protein: Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dualspecificity protein phosphatase Cytogenetic locus: 10q23 Inheritance: AD

In assessing the diagnostic criteria for Peutz-Jeghers syndrome, physicians look for classic features such as gastrointestinal polyposis, benign and malignant sex cord tumors, and cancers of the breast, colon, pancreas, stomach and other organs. Which of the following genes would you test in a patient who meets the diagnostic criteria?

STK11

Deletion 9q34

Severe learning difficulties Hypotonia Obesity Brachycephaly (abnormal skull length) and microcephaly Arched eyebrows Anteverted nostrils and a pouting lower lip Prognathism - bulging of the lower jaw Sleep disturbances Behavioral problems Epilepsy Urogenital defects Psychiatric disorders Severe speech delays

Loeys-Dietz syndrome

TGFBR1/2, SMAD3 (AD) vascular findings (tortuosity), joint laxity, hypertelorism

Tuberous sclerosis complex

TSC2 occurs 70% of the time Mutations of TSC2 lead to more serious disease Benigh tumors of the brain, skin, kidneys, eyes, heart, or lungs, seizures, coughing, shorting of breath, hypomelatonic macules, shagreen patches and ungual fibromas, DD & ASD, pitted teeth, congenital cardiac rhabdomyomas, thick skin patches variable expressivity AD, mostly de novo1/6000

X-linked dominant

a mode of genetic inheritance by which a dominant gene is carried on the X chromosome

Y-linked

The pattern of inheritance that results from genes located only on the Y chromosome. examples: -Retinitis Pigmentosa linked to the RPY gene -Jacobs Syndrome (XYY) -Hypertrichosis Pinnae (excessive ear hair)

Trisomy 13 (Patau Syndrome)

The presents of Holoprosencephaly, chromosomal condition associated with sever intellectual disability and physical abnormalities, cells in the body contain extra genetic material from chromosome 13, this abnormality increased with maternal age?

CPIC guidelines

They do NOT tell you when to order a test or when reimbursement happens standardized, peer reviewed, free on PharmGKB, updated, authorship with COI policy, closely follow IOM practices, published in Clinical Pharmacology and Therapeutics

ABC transporters can become mutated and overexpressed resulting in multidrug resistance in cancer. True or False?

True

Both professional organizations and regulatory bodies have responsibility for setting guidelines for confidentiality and its limitations. true or false?

True

Common triggers of a metabolic crisis include catabolic stress, diet, fasting, or medications Tre or false?

True

Miller-Dieker Syndrome

Type 1 lissencephaly (smooth brain) LIS1 ID, microcephaly, feeding difficulties, hypotonia, spasticity dysmorphic facies frontal bossing,small jaw early childhood death, no developmental milestones 50% visible deletion 17p13.3 partial monosomy maybe balanced translocation (17q:17p or 12q:17p)

Aicardi Syndrome

VERY RARE (prevalence only thousands) XLD inheritance (lethal to XY, but those with Klinefelter's XXY may survive)3 key feats: - Agenesis of the corpus callosum - Intractable seizures (severe infantile spasms) - Lacunar retinopathy Other feats: - severe GDD/mental retardation - pulmonary dysfunction (recurrent infections)- increased cancer risk, esp hepatoblastoma - cleft lip/palateIx: - EEG shows characteristic short burst + suppression pattern arising from each hemisphere (not hypsarrhythmia) - MRI shows absence of corpus collosum VERY poor prognosis (death within first decade)

Aicardi syndrome

VERY RARE (prevalence only thousands) XLD inheritance (lethal to XY, but those with Klinefelter's XXY may survive) 3 key feats: - Agenesis of the corpus callosum - Intractable seizures (severe infantile spasms) - Lacunar retinopathy Other feats: - severe GDD/mental retardation - pulmonary dysfunction (recurrent infections) - increased cancer risk, esp hepatoblastoma - cleft lip/palate Ix: - EEG shows characteristic short burst + suppression pattern arising from each hemisphere (not hypsarrhythmia) - MRI shows absence of corpus collosum VERY poor prognosis (death within first decade)

Limb-girdle dystrophy (LGMD)

Weakness and muscle wasting in arms and legs Variable severity, age of onset and features Unusual gait, wheelchair may be needed Changes in posture or appearance of shoulders, back and arms Scapular winging Lordosis or scoliosis Joint contractures - restricting movement in hips, knees or elbows Hypertrophy of the calves Cardiomyopathy Mild to severe breathing problems sometimes requiring a ventilator Intelligence is generally unaffected Can be AD or AR - once Becker or DMD is ruled out, immunostaining on muscular tissue can be done to diagnose this type

WAGR syndrome

Wilms tumor is a rare renal embryonal neoplasm Aniridia - absence of iris of the eyeGU abnormalities ID - autism, ADD, OCD, anxiety and depression Early obesity onset and cholesterol levels have been seen too Growth restriction Interstitial deletion of 11p13confirmed with array CGH or FISH - WT1 gene Undescended testes in males, streak gonads and heart shaped (bicornuate) uterus in females

Incontinentia Pigmenti

X linked dominant, mutation in the IKBKG gene, lethal in males, rashes and blisters early in life, possibly learning disabilities and retinal detachment, rash portions of skin are places that have the good X inactivated (female mosaics)

Incontinentia Pigmenti

XLD inheritance (typically lethal in boys)Mutation in IKBKG or NEMO gene on ChXq28. IKBKG protein activates NF-kappaB which protects against TNF -alphaFeats: - Skin lesions usually involving trunk/extremeties. Starts as blistering or wart-like rash, then develops into hyperpigmented swirling macular lesions. Eventually regress to form linear hypopigmented lesions - Alopecia - Hypodontia (teeth failure) - Dystrophic nails - Neuro (motor delay, seizures) - Bones (hemivertebrae, scoliosis)

A 4-year-old boy presents to clinic with several hyperpigmented lesions of the skin. Upon further evaluation, an ophthalmologist detects Lisch nodules. You also are told that the patient's mother has these same skin findings, and had trouble learning when she was in school. What condition does the patient most likely have?

Xeroderma Pigmentosum

Isochromosome

a chromosome that has lost one of its arms and replaced it with an exact copy of the other arm

Mosaicism

a condition in which cells within the same person have a different genetic makeup.

Medel's Law of Segregation

allele pairs separate or segregate during gamete formation, and randomly unite at fertilization.

Considering a syndrome that causes large for gestational age (LGA) newborn infants with subsequent overgrowth, large tongue, omphalocele, and predisposition to Wilms tumor, which of the following statements is false? A. This syndrome is also known as Beckwith-Wiedemann syndrome B. Some cases are due to imprinting, due to uniparental disomy of an entire chromosome C. This syndrome is caused, at least in part, to underexpression of a gene product D. Activation of a normally imprinted gene can result in this syndrome E. The increased expression of the insulin like growth factor (IGF2) gene is thought to be responsible for the overgrowth features in this syndrome

Which of the following best defines first pass metabolism? A. Introduction of functional groups to provide substrate for Phase 2 metabolism B. Activation of prodrugs through phase 1 metabolism C. Metabolism of ingested xenobiotics before the reach systemic circulation D. Drug inactivation in the liver by CYPs

CRC is a major feature in FAP, Peutz-Jeghers syndrome, and gastrointestinal stromal tumors (GIST) True or false?

false

disorders of pyruvate metabolism affect what?

carbohydrates

A young woman delivers a baby, and fairly soon after develops some new neurological symptoms. It is suspected that she might have post-partum depression, but she then has a seizure, becomes comatose, and has some brain swelling. the patient passes away when the brain swelling becomes extreme. This occurs as her uterus is shrinking after the delivery. What is the mechanism for this? Check all that apply. catabolism liver failure hormonal change psychological stress protein overload

catabolism protein overload

tumor type; PTEN hamartoma syndrome

cerebellar gangliocytoma

Thanatophoric dysplasia

children are usually stillborn or die shortly after birth from respiratory failure; a few affected individuals have survived into childhood with extensive medical help. • Characterized by extremely short limbs and folds of extra (redundant) skin on the arms and legs. • Other features include a narrow chest, short ribs, underdeveloped lungs, and an enlarged head with a large forehead and prominent, wide-spaced eyes. • Autosomal dominant and new mutation• Two major forms of thanatophoric dysplasia, type I and type II. • Type I is distinguished by the presence of curved thigh bones and flattened bones of the spine (platyspondyly). • Type II is characterized by straight thigh bones and a moderate to severe skull abnormality called a cloverleaf skull.

PKU (phenylketonuria)

chrom 12 mutation leads to error in converting phenylalanine to tyrosine; ClinMan: fail to meet dev milestones, microcephaly, progressive neurological decline/MR, seizures, hyperactivity, LD, eczema. Diag: serum phenylalanine by 3 days old. -Treatment: diet low in protein and starches, gene therapy, phenylalanine lowering agents.

What test should be ordered for unexplained SB or neonatal death? Esp if occurs with growth restriction of one other anomaly?

chromosome studies with microarray CGH

Hardy-Weinberg equilibrium

condition that occurs when the frequency of alleles in a particular gene pool remain constant over time

PharmGKB what is it

curates knowledge on topic of PGX for physicians and clinicians to access.

CGH or chromosomal microarray

del/dup less than 1-2 Mb can detect small dels and dups of "apparently balanced" translocations at or near site of breakpoint (karyotype is best method for balanced translocations) if SNPs, identifies LOH (UPD, consanguinity, incest) standard of care for ID work-up per ACMG https://www.acmg.net/docs/ACMG_Lab_Standards_and_Guidelines_CMA_Revision_2013_GIM_112013.pdf

Costello syndrome

failure to thrive (feeding difficulties), hypertrophic cardiomyopathy, valvar pulmonic stenosis, arrhythmias, 15% lifetime malignancy risk AD

"Questioning," "interested," and "curious" are examples of feeling words. true or false?

false

An antagonist will activate the target it binds to. true or false?

false

An individual with 45 chromosomes and a Robertsonian translocation between both copies of chromosome 21 can have live born children with a normal karyotype or with trisomy 21.

false

BARD1

gene mutation found in families that look like HBOC but dont have BRCA1/2 mutations, women with mutation have increased risk for breast cancer Breast, ovarian, and pancreatic - exact risk unkown

BRIP1

gene with increased ovarian cancer risk, uncertain risk increase for breast ca AR disease: Fanconi Anemia

medals law of independent assortment

genes on nom-homoligus chromosomes are sorted independently of each other during gamete formation

Hereditary Peripheral neuropathies

group of inherited disorders affected peripheral nervous system - can be divided into 4 categories: motor and sensory neuropathy, sensory neuropathy, motor neuropathies, sensory and autonomic neuropathy

Chromosome breakage syndromes

increase susceptibility to cancer development, increase sister chromatid exchange - normally 10 exchanges per cell, in syndromes its greatly increasedex: Ataxia telangiectasia, Bloom syndrome, Nijmegen syndrome, Fanconi anemia, Xeroderma pigmentosum (XP)

autosomal dominant

inheritance pattern of a dominant allele on an autosome

Spinal Muscular Atrophy (SMA)

leading cause of death in infants causes loss of motor neurons and muscle wasting scoliosis and joint contracturesSMN1 is most common - AR

Coffin-Siris syndrome

learning disabilities, mild to severe limited language development, hypoplasia of the 5th digit, absense of nails, coarse facies affecting brows, lashes, and hairline, microcepaly.

Individuals with a CDH1 gene mutation are more likely to have which of the following type of breast cancer histology?

lobular

A chromosomal analysis is obtained on a young woman with mild signs of Turner syndrome and reveals a 46,XX/45,X karyotype. Nondisjunction is most likely to have occurred in

miosis after fertilization

Charcot-Marie-Tooth disease

most common hereditary motor and sensory neuropathy (HMSN) ADage of onset 10-30slow progressive distal muscle weakness in lower limbs, ataxia, tremor, absent peripheral nerve reflexes, exaggerated foot arch

MELAS

mtDNA (ATPase subunit 6 gene)neuropathy, ataxia, RP, DD/ID, lactic acidemia

amniotic band syndrome

multiple fibrous strands of amnion that develop in utero that may entangle fetal parts to cause amputations of digits, arms and legs Occurs in 1st trimester

BRIP1, RAD51C, RAD51D

mutations are associated with high susceptibility to ovarian cancer

Motor neuron disease

nerves in spine and brain lose function symptom onset after age 40 males affected more ALS most common type (affects upper and lower neurons - legs, mouth, arms and respiratory muscles

Deletion 16p11.2

one of the most common deletion syndromes Developmental delay and ID, sometimes ASD (found in 1% of those with autism)Expressive language delay Epilepsy Low set ears Partially webbed toes Hypotonia Obesity Large head circumference Signs and symptoms vary amongst individuals and families and some people may not know they have the deletion

Oral contraceptives can reduce the risk to develop which of the following cancers?

ovarian and endometrial

Sara and Mark are first cousins.Assume Mark has the deleterious allele (a). What is the chance that Sara also inherited the allele from a common ancestor?

p(inherited from grandmother): (1/8) (1/2) = 1/16p(inherited from grandfather): (1/8) (1/2) = 1/161/16 + 1/16 = 1/8

fetal alcohol syndrome

physical and cognitive abnormalities in children caused by a pregnant woman's heavy drinking

Lysosomal storage disorders

progressive, enzyme missing, substrate accumulatesincreases mass of tissues/organs (hepato/splenomegaly)neurodegeneration50 typesenzyme replacement therapyTay Sachs, Sandhoff disease (HEXB)

organic acidemias affect what?

proteins

A man w/FHx of CF wonders about his risk of having an affected child.Probability that his spouse is a carrier?

q² = 1 in 2500 q = 1 in 50 p ≃ 12pq = 1 in 25

ring formation

single chromatid's ends unite to form ring

Deletion 1q21.1

some people do not appear to have associated features - some may not know they have the deletion -Developmental delay and mild ID 75% - especially with motor skills Prominent forehead, large rounded nasal tip, long philtrum, high arched palate, microcephaly Short stature Cataracts Bone abnormalities - especially in hands and feet Hearing loss Heart defects - less frequent Abnormalities of genitalia

xlinked recessive

sons of heterozygous mothers have a 50% chance of being affected. No male-to-male transmission. Females usually must be homozygous to be affected

In which of the following population groups is there an increased carrier frequency for alpha thalassemia, beta thalassemia, and hemoglobin E? A. Greek Americans B. Sardinians C. Equatorial Africans D. Southeast Asians E. All of the above

southeast Asians

Recombination

the genetic process by which one chromosome breaks off and attaches to another chromosome during reproductive cell division

which of the following is an example of a type of driver gene that plays a role in cell division and death? A. Chromosome segregation B. Transcription factors C. DNA methylation D. miRNA

transcription factors

Client emotional issues may create resistance in the interviewing process. true or false?

true

Confidentiality has to do with the rules for sharing client information by the interviewer. True or false?

true

DNA testing without RNA testing makes it more difficult to classify variants because it can miss deep-intronic mutations true or false

true

Effective interviewer listening helps clients listen to others more effectively. True or False?

true

Effective listening can help clients find new meaning in their lives. true or false?

true

Interviewers should expect that resistance will differ from culture to culture. true or false?

true

You meet with a 37-year old woman in the breast center regarding her family history of cancer. She reports that her paternal aunt was diagnosed with breast cancer at age 45. She also reports that she has a personal history of a breast biopsy, which revealed atypical hyperplasia. Which of the following models would give the MOST accurate estimation of her breast cancer risk?

tyrer-cuzick

BRCAPRO Model

used for high risk women to assess risk of BRCA1 and BRCA2 mutation in given family

Gail Model Risk Assessment Tool

used to estimate any woman's 5 year and lifetime breast cancer risk

Becker muscular dystrophy (BMD)

very similar to, but less sever than, Duchenne muscular dystrophy

Holoprosencephaly (HPE)

• Can be classified as chromosomal, syndromal, or isolated • Cephalic disorder in which the prosencephalon (the forebrain of the embryo) fails to develop into two hemispheres. • Normally, the forebrain is formed and the face begins to develop in the fifth and sixth weeks of human pregnancy. • In holoprosencephaly the result is a single-lobed brain structure and severe skull and facial defects • The most common chromosomal abnormality associated with HPE is trisomy 13, although a number of other chromosomal changes can also cause holoprosencephaly including deletions, duplications and triploidy • Syndromal causes include deletion 22q11 (DiGeorge) syndrome and Smith-Lemli Optiz syndrome • Isolated holoprosencephaly is sometimes explained by heterozygous mutations in three genes with variable effects which are Sonic hedgehog (SHH) on chromosome 7q36, ZIC2 on chromosome 13q32 and SIX3 on chromosome 2p21.

Mowat-Wilson Syndrome

• Caused by mutations in the ZEB2 gene which provides instructions for making a protein that plays a critical role in the formation of many organs and tissues before birth. • It is involved in the development of tissues that give rise to the nervous system, the digestive tract, facial features, heart and other organs. • Autosomal dominant • Intellectual disability • Distinctive features

Cornelia de Lange Syndrome (CdLS)

• Developmental disorder that affects many parts of the body. The features of this disorder vary widely among affected individuals and range from relatively mild to severe. • Characterized by slow growth before and after birth leading to short stature; intellectual disability that is usually moderate to severe; and abnormalities of bones in the arms, hands, and fingers. • Most affected individuals also have distinctive facial features including:• long arched eyebrows that often meet in the middle (synophrys), • long eyelashes, • low-set ears, • small and widely spaced teeth , • a small and upturned nose. • Many affected individuals also have behavior problems similar to autism, a developmental condition that affects communication and social interaction. • Additional signs and symptoms of Cornelia de Lange syndrome can include: • excessive body hair (hypertrichosis), • an unusually small head (microcephaly), • hearing loss, and problems with the digestive tract. • cleft palate. • Seizures, heart defects, and eye problems have also been reported in people with this condition.

Sotos syndrome (cerebral gigantism)

• Previously known as cerebral gigantism or overgrowth syndrome • Characterized by a distinctive facial appearance, • Overgrowth in childhood including advanced bone age • Learning disabilities or • Autosomal dominant but most are new mutations • Mutations in the NSD1 gene are the primary cause of Sotos syndrome, accounting for up to 90 percent of cases. • delayed development of mental and movement abilities. Characteristic facial features: • a long, narrow face; • a high forehead; •flushed (reddened) cheeks;• small, pointed chin.

Pitt Hopkins Syndrome

• Rare genetic disorder characterized by:• developmental delay, • epilepsy, • distinctive facial features, and • possible intermittent hyperventilation followed by apnea. • As more is learned about Pitt-Hopkins, the developmental spectrum of the disorder is widening, and can also include difficulties with anxiety, autism, ADHD, and sensory disorders. • It is associated with an abnormality within chromosome 18; specifically, it is caused by an insufficient expression of the TCF4 gene

Wiedmann-Steiner syndrome

• Rare genetic disorder that causes developmental delay, unusual facial features, short stature, and reduction in muscle tone. • All cases reported so far are sporadic.

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