Weird Named Diseases

MEN 2A

"Sipple syndrome" -germline mutations in the *RET* protooncogene on chromosome 10q11.2 -*medullary carcinoma of the thyroid* and C-cell hyperplasia. -*pheochromocytoma*, often bilateral -*parathyroid adenomas* *Picmonic*: two apple men with thyroid medal, parachute jumper and crashed car in front of the roulette RET table.

MEN 2B

"Wagenmann-froboese syndrome" germline mutation in the RET protooncogene on chromosome 10q11.2 1. *medullary carcinoma of the thyroid* and C-cell hyperplasia. 2. *pheochomocytoma* 3. *ganglioneuromas of oral mucosa* (also involve skin, eyes, GIT, and respiratory tract) 4. *Marfan body habitus* *Picmonic* two men in black at the roulette Ret wheel in the chrome fiat with neurons with mouths, with the thyroid medal and Marvin the martian Lincoln.

Diseases with deficient DNA repair enzymes

*Ataxia telangiectasia* - DNA hypersensitivity to ionizing radiation. *Xeroderma pigmentosa* - DNA hypersensetivity to UV radiation, causing premature skin aging and increased risk of cancer. *Fanconi Anemia* hypersensitivity of DNA cross linking agents. *Bloom syndrome* generalized chromosomal instability *HNPCC* defect in DNA mismatch repair enzymes so increased colorectal cancer.

Fragile X Syndrome

*CGG* trinucleotide repeat expansion. FMR1 gene mutation. -shows anticipation as the repeats get longer though generations. -*X-linked dominant* mcc of *inherited intellectual disability*. -mental retardation / autism /ADHD -m.c. single gene cause of Autism spectrum disorder -long narrow face -*macroorchidism*. -large prominent jaw -protruding ears, mitral valve prolapse, joint abnormalities, patent eustachian tube. *Picmonic:* man with X-lunchbax, near short bus with balls.

Prader-Willi syndrome

*Maternal imprinting* and then inheritance of mutated allele from father of chromosome 15. -hypotonia or "floppy baby" -feeding difficulties when young -intelectual difficulties -Older then *hyperphagia - obesity - type II DM* -hypogonadism, (small penis/testis, cryptorchidism. -*almond shaped eyes* - downward turned *fish-like mouth* -truncal obesity -*increased Grehlin* associated with an increased risk of sleep apnea, type II DM, and gastric rupture. *Picmonic* prada purse with mother stamping her approval, fajita hiker and hypogonadal hippo in truncal obesity tree.

Turner Syndrome

*Monosomy X* Webbed neck (d/t cystic hygroma) short stature swollen hands and feet at birth (lympahdenoma) aka congenital lymphedema. shield chest and wide nipple spaces. nail dysplasia gonadal dysgenesis (streak gonads) cardiac defects - *bicuspid aortic valve, coarctation* -*Decreased estrogen, increased FSH and LH* -dysgerminomas -Horseshoe kidneys -*primary amenorrhea* increased risk of osteoporosis (lack of estrogen). *Picmonic*: turnip with cystic hygroma sisters. Genie ovaries dysgenesis, edamame hands, down easter egg with up arrow fish on lounge. tampon and orca whale.

Niemann-Pick disease

*Sphingomyelinase deficiency* autosomal recessive, Ashkenazi jews. onset between ages 2-6 months. -*Hepatosplenomegaly and areflexia* (the only difference between this and Taysachs) -loss of motor milestones -hypotonia -feeding difficulties -*cherry red macula* -foam cells seen on histologic examination. *Picmonic*: man with cherry eyes, foaming mouth and pick in knee

Duchenne muscular dystrophy

*X-linked recessive* deletion of dystrophin gene on *chromosome 21.* -onset is 2-3 y/o *the youngest onset of all MD's* -progressive weakness - Positive *Gower maneuver.* -*calf pseudohypertrophy* comorbidities are scoliosis and cardiomyopathy. labs: *increased CPK and aldolase* wheelchair bound by adolescence and death by 20-30. *Picmonic:* muscle suit man with disc trophy and ataxic gait with dead heart and lungs

AIRE

*autoimmune regulator*: is a protein encoded by the AIRE gene. it is a TF expressed in the medulla of the thymus and is involved in T-cell negative selection. Leads to *autoimmune polyendocrine syndrome 1* -AR on chromosome 21 this can lead to: -hypoparathyroidism -primary adrenocortical failure -*chronic mucocutaneous candidiasis* (constant candida infections and increased HPV infection) *Picmonic* for chronic candidiasis, green chrone with HPV and candida owl.

IL-12 receptor deficiancy

*decreased Th1 response* AR -increased infections -*decreased INF-y* - disseminated mycobacterial and fungal infections. -may present after administration of *BCC vaccine* - decreased IL-12, decreased Th1 - decreased INF-y - decreased macrophage activation - *decreased TB clearance* *Picmonic* - locked egg carton with macrophage mack man. decreased IGF-grandma and increased bacteria and microbes.

Wiskott-Aldrich syndrome

*inability of T-cells to re-organize their actin cytoskeleton* - inefficient T-cell and B-cell function. X-linked recessive. 1. *recurrent infections* 2. *thrombocytopenia* decreased number and decreased size 3. *eczema* decreased IgM, normal IgG, increased IgE and A WATER = wiskott Aldrich thrombocytopenia eczema recurrent infections. *Picmonic* whiskey alter with eczema zebra putting t and B cells to death. side toe peanut with decreased IgM hiker and pointing IgA and IgE goblins.

Pierre-Robin Sequence

-*Micrognathia* hypoplasia of the mandible -*Glossoptosis* posterior displacement of tongue prevents palatal fusion. -U-shaped *cleft palate* -complications include *recurrent otitis media* and *upper airway obstruction* that often lead to tracheostomy. -first and sometimes second pharyngeal pouch derivatives have a failure of neural crest cell migration -*Picmonic* none specific

Cornelia de Lange (Brachmann-de Lange) syndrome

-*single eyebrow* -very short stature without skeletal abnormalities. -sporadic inheritance but some AD -small for gestational age and FTT -infantile *hypertonia* -mental retardation -cardiac defects -*autistic-like features* lack facial expression and have self-destructive tendencies. -*craniofacial*: single eyebrow (synophrys), microcephaly, thin down-turned upper lip and micrognathia *no picmonic*

Klumpke's Palsy

-damage to C8-T1 -usually due to lower trunk of the branchia plexus that gives rise to axillary, radial ulnar and part of the median nerves. -upward force on babies abducted arm during delivery. this is stretching the axilla. -adult is reaching for a tree branch to break a fall -intrinsic muscles of the hand are affected, such as the thinner and hypothenar eminence. -you get total claw hand because lumbricals are unable to flex at the metocarpophalangeal joints or extend at the proximal or distal interphalangeal joints.

Erbs Palsy

-damage to roots C5 and C6 -musculocutaneous, axillary, median and radial nerves. and suprascapular nerves -damage to upper trunk of the brachial plexus -MOA: stretching babies neck during delivery. -pulling shoulder during a breech delivery -adults is more trauma to neck that injury upper nerve -deltoid injured that is innervated by axillary nerve. -infraspinatus innervated by the supra scapular nerve. -biceps brachii, innervated by the musculoskeletal nerve. -waiters tip deformity - arm is medially rotated, adducted, and extended with forearm pronated.

Turcot Syndrome

1. Familial adenomatous polyposis 2. CNS tumors (medulloblastomas, glial tumors)

Gardner Syndrome

1. Familial adenomatous polyposis 2. fibromatosis 3. osteomas (benign) aka osseous and soft tissue tumors 4. impacted supernumerary teeth 5. congenital hypertrophy of retinal pigment epithelium

plummer-Vinson Syndrome

1. iron deficiency anemia 2. esophageal web 3. *dysphagia* and have a beefy red tongue due to atrophic glossitis *Plummers DIE*

DiGeorge Syndrome

22q11.2 deletion -conotruncal heart defects (trunkus arteriosus; tetrology of fallot, VSD) -abnomal facies: short palpebral figure, small shin and ear anomalies. -thymic aplasia / hypoplasia d/t deficiancy in neural crest cell migration and *pharyngeal pouches 3 and 4* -T-cell deficiency and therefore increased viral and fungal infections -cleft palate -hypocalcemia. (B cells are normal) CATCH 22 - cardiac abnormalities, abnormal facies, thymic hypoplasia, cleft palate / cellular immune deficiency, hypoparathyroid with hypocalcemia *Picmonic* curious george monkeys with pouches, thigh plate, calcium cow, parathyroid parachutes and fungus and virus friends.

Klinefelter's syndrome

47, XXY aneuploidy -*Eunuchoid body shape*, tall, long extremities and wide hips. -mild mental retardation and struggle in sports -*gynecomastia* with female hair distribution -*testicular atrophy* - primary hypogonadism and decreased testosterone -small penis -dysgenesis of seminiferous tubules, aka where sperm mature. -*decreased inhibin* -*increased FSH and LH* -Leydig cells that produce testosterone are dysfunctional, so *decreased production of testosterone* and increased LH. -the serum increase in FSH leads to increased aromatase and therefore *increased estrogen*. -Barr body seen *Picmonic:* calvin klein model with feather. LH and FSH upwards, with upwards easter egg and barr body.

Peutz-Jeghers Syndrome

AD - mutation in STK11 gene 1. *Hamartomas* throughout GIT tracks - benign 2. *Mucocutaneous hyperpigmentation* - on lips, oral mucosa, and genital skin -increased risk for colorectal cancer, breast cancer, and gynecological cancer. *Picmonic* - mini gold with pigmented pig and jaguar golfers with bee in the water and benign bunny on colon of hammerhead sharks.

Neurofibromatosis (NFT) Type 2

AD NF2 tumor supressor gene codes for the protein *MERLIN on chromosome 22* - *bilteral acoustic shwanommas* - *meningiomas* - *ependymoma* - tumor from emendymal cells, usually in 4th ventricle or spinal canal - hydrocephalus. -cataracts -Cafe Au Lait spots *Picmonic* Fabio in jeans, on giant swan, panda mummy and cafe cow in cataract cadillac.

Bloom syndrome

AR *mutation in BLM* gene encoding *helicase* an enzyme that unwinds DNA during replication. SxS: growth retardation, facial anomalies, photosensitive skin rash, immunodeficiency and chromosomal instability and breakage. *Picmonic* none

Schwachman-Diamond Syndrome

AR condition decreased neutrophil chemotaxis, cyclic neutropenia, and pancreatic exocrine insufficiency. patient presents with recurrent soft tissue infection, chronic diarrhea, and FTT. exocrine pancreas insufficiency with malabsorption, short stature caused by metaphysical chondrodysplasia and neutropenia.

Ataxia telangiectasia

AR disorder characterized by combined immunodeficiency, cerebellar ataxia, oculocutaneous telangiectasias, and predisposition to malignancy. mutation on *chromosome 11* Defects in ATM gene = *failure to repair DNA double strand breaks* and cell cycle arrest. Traid: -Ataxia = cerebellar defects - spider angiomas -IgA deficiency tests: -increased AFP -non homologous end joining is damaged. decreased IgA, IgG and IgE. increased chance of cancer *Picmonic* spider taxi with cerebellar bell, DNA repair man falling from ATM and tumor factor stepping on IgA.

Jervell and Lange-Nielson Syndrome

AR disorder that causes *QT interval prolongation.* -this is caused by potassium channel defects, that delay repolarization on heart muscle. -can cause syncope, torsades de pointes, arrhythmia and death. -associated with *severe B/L sensorineural hearing loss* -refrain from vigorous sports -can but on B-blocker to blunt exertional HR and shorten QT interval. long QT if it is longer than half the RR interval.

Von Gierke Disease

Alos glycogen storage disease type I. buildup of glycogen in certain tissues caused by a glucose 6 phosphate deficiency. onset in 3-4 months. *Liver, kidneys, intestinal mucosa* -increased uric acid and lipids -decreased BGL - seizures -lactic acidosis -hepatomegaly -doll like face (round cheeks) -thin extremities -spleen and heart are never involved. *Picmonic*: Van Jerky with the unicorn and doll

Hyper IgE Syndrome ak Job Syndrome

Also autosomal dominant *hyper IgE syndrome*. STAT3 gene mutation (JAK-STAT pathway) -d/t *Th17 cells* lacking the ability to signal other immune cells resulting in abnormal chemotaxis d/t a deficiency in INF-gamma production -T-cells cannot signal other immune cells d/t deficiency in INF-gamma production. -decreased TH1 differentiation. - *Leonine facies* - Red hair - Eosinophilia - Eczema - cold / noninflammed staph abscesses - Teeth issues *retained baby teeth* two set of teeth - lab has increased IgE *Picmonic:* INF-Gamma deficiency grandma, IgE electric goblin in suit, lion in red hair with blue retainer teeth goblin with skin rash.

Myotonic Dystrophy

Autosomal dominant trinucleotide expansion of *CTG* trinucleotide repeat - has a unique mode of inheritance so onset is 12-30 y/o *oldest age of onset* -*facial weakness* -*dysphagia* -*testicular atrophy* -hand grip myotonia -cataracts -balding -death from respiratory or heart failure *Picmonic* muscle man on disk with toupee man gripping trophy, in cataract cadillac with can trophy gold repeat. naked boy with balls.

Marfan disease

Autosomal dominant disease *FBN1 gene mutation* on chromosome 15 -*normal intellect* -*aortic root dilation* -*upwards dislocation of lens* (3 above are unique to marfans and set it apart from homocystinuria) Fibrillin-1 gene mutation, which is an extracellular matrix component. Tall males, arachnodactyly (long fingers), precuts excavatum, hypermobile joints, aortic aneurysm and dissection, MVP, superior subluxation of lens, scoliosis M: mitral valve prolapse A: aortic R: root dilation (avoid contact sports) F: fibrillin and chromosome fifteen A: aneurysms N:aneurysms S: draw arrow on the edge, and lens goes up and out *Picmonic*: basketball player with frog in net and MVP with orca coach

Galactosemia

Autosomal recessive deficient: galactose-1-phosphate uridyl transferase -*Jaundice* -*vomiting* -*hepatomegaly* -*hypoglycemia/convulsions* -*bilateral cataracts* failure to thrive, encephalopathy. labs: increased LFT's, coaguloathy, metabolic acidosis, increased plasma galactose, urine is positive for reducing substances. *sepsis d/t E coli* is principal cause of early mortality. Dx - nonglucose reducing substances in urine. *Picmonic* the SONG!!!

Friedrich Ataxia

Autosomal recessive. Excessive trinucleotide repeats of *GAA* in the frataxin gene. Reduced protein produced by frataxin gene causes mitochondrial instability. Onset is *before 22 y/o* wheelchair by 25 and death by 30-35. combination of: -*hammer toes* - defect in proximal IP joint -Pes Cavus - high arch deformity -Kyphoscoliosis -Latetal corticospinal tracts -posterior column -Spinocerebellar tract -Associated with type I DM -*Hypertrophic cardiomyopathy - m.c.c of death* *Picmonic:* Fred flinstone with hammertoes carrying chocolate with mitochondria taxi, with GAA lights above garage, and all the spinal signs.

Tay sachs Disease

B-hexosaminidase A deficiancy -autosomal recessive, Ashkenezi jews -onset between 2-6 months *hyperreflexia* (only difference between this and Niemann Pick) -loss of motor milestones -hypotonia -feeding difficulties -*cherry red macula* *Picmonic*: Taylor swift on car with onion taxi driver, and gangster on side with hexagon A wheels.

Hyper IgM Syndrome

Can be X-linked or autosomal recessive X-linked: defect in *CD40 ligand,* which causes failure of isotope class switching. -The CD40 ligands on helper T cells attach to the CD40 receptor on B cells, working to activate B-cells to produce specific immunoglobulins for pathogen defense. here there are defective CD40 ligands on their helper T cells, and subsequently the b-cells cannot be activated to Ig switch out of IgM. *This is a T-cell cause* sinopulmonary infections and opportunistic infections. *huge increase in IgM and huge decrease in IgG, A and E* -common pyogenic abscess formation *Picmonic*: mountain goblin bullying the class, rest of the Ig's. not allowing to switch class and stepping on CD40 Ligand between B and T cells.

Sturge-Weber Disease aka encephalotrigeminal angiomatosis

Congenital, non-inherited developmental anomaly of *neural crest cell derivatives*, d/t activating mutation of *GNAQ gene*. embryonal developmental abnormality - error in mesoderm and endoderm -affects small (capillary sized) blood vessels that create *port wine* stains on the face (nervous flemmeus, a non-neoplastic birthmark in the CN V1 V2 distribution) these grow in children instead of disappearing. -ipsilateral leptomeningeal angioma under the port wine stain (abnormal proliferation of blood vessels in the leptomeninges) -AV malformations -seizures -intellectual disability -episcleral hemangioma -increased IOP that leads to early onset glaucoma -can have phoechromocytoma - tram track calcifications on opposing gyri *Picmonic* sturgeon in the web with the seizure shooting the glaucoma gun

Leukocyte adhesion deficiency

Defect in *CD18*, which is repressible for making *LFA1 integrin* on the WBC surface, which allows neutrophils to attach to *ICAM* on endothelial cells and make their way out of the bloodstream. 1. Delayed umbilical cord seperation (>3 wks) 2. Recurrent skin and mucosal bacterial infections - but without purulence - NO PUS aka *non pyogenic* 3. severe periodontal disease. Other: increased leukocytosis with neutrophil predominance, d/t inability to exit bloodstream. delayed wound healing. *picmonic* luke adhered to wall, ICAM with defective CD with 1 wand and 8 ball, trojans hanging from umbilical cords and nun throwing pies.

WAGR Syndrome

Deletion on chromosome II - loss of several genes. -*W*ilms tumor -*A*niridia (absence of iris aka colored part of eye) - photophobia, other eye issues. this is typically the first noticeable sign of WAGR syndrome. -*G*enitourinary abnormalities: M>F. males have cryptochidism. females have streak gonads and bicornate uterus. -*R*etardation: difficulty processing, learning, psych and behavioral problems. other issues: obesity, pancreatitis, renal failure. *Picmonic* none

Heyde's Syndrome

GI bleeding from angiodysplasia in the presence of aortic stenosis. -caused by the induction of VWB disease type IIA -depletion in vWBF in blood flowing through narrowed valvular stenosis. *not for step one*

SCID (autosomal recessive)

Group of inherited disorders characterized by profoundly defective T and B cell dysfunction. Less common form of SCID. *adenosine deaminase (ADA) deficiency* - build-up of dATP - inhibits ribonucleoside reductase. -Purine nucleoside phosphorylase deficiancy. -RAG deficiency (VDJ recombination) nonsense mutation in VDJ = SCID. missense of VDJ recombination = Omenn syndrome. "Omenn syndrome:" -bright red rash on head. -wrinkled skin with edema -deficiency of B and T cells. -failure of the thymus to develop - *chronic recurrent diarrhea* -PNA -Thrush -failure to thrive -LAD, hepatosplenomegaly. *Picmonic:* Wolverine in front of skid marks with t and B balls and microbes falling out. with the chained up dentists and dog and bone train plant.

Henoch-Schonlein Purpura

IgA mediated vasculitis with a classic triad of: -palpable purpura on LE -arthralgias (ankles and kneed) -abdominal pain - "colicky" -renal disease - IgA nephropathy. other things: GI hemorrhage and intussusception (black tarry stools). *Picmonic:*hen, monk, purple cat with URI & stool

MELAS

MELAS - mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) mitochondrial genetic mutations, both normal and abnormal mitochondrial DNA. *mitochondrial encephalopathy, lactic acidosis, stroke-like episodes*. this explain a young person with multiple strokes and increased serum lactate levels. (often in other mitochondrial defects you see ragged red muscle fibers on biopsy). *Picmonic* none

Ehlers Danlos Syndrome

Multiple defects in Collagen synthesis - there are multiple subtypes with differing collagen mutations. either AR or AD there are six different types, the most common being *V* and then type III. -*hypermobile joints and hyper-elastic skin* -easy bruising and bleeding - fragile vessels with *tissue paper thin scars* once injury begins to heal. -*Berry aneurysm* - GI issues - constipation, rectal prolapse and hemorrhoids. types: -*I and II* lead to type V collagen defect - skin and joint manifestations -*III* the most common type, joint instability and hypermobility -*III* can also cause organ rupture and see through skin *Picmonic* there are two-the Ellen Degenerous show, with the Cola man and the mobile hiker.

Fanconi Anemia

Not the same as Fanconi Syndrome of the proximal renal tubules. This is a type of *aplastic anemia* congenital DNA repair defect causing BM failure, either autosomal recessive or X-linked. -pancytopenia: aplastic anemia (fatigue, pallar, increased infections, bleeding. -appearance: short stature, microcephaly, *abnormal thumbs*. -skin: hyper/hypopigmented areas, cafe-au-alit spots. -eyes/ears: strabismus, middle ear abnormalities. deafness, chronic otitis media. -thumb and radial defects *Picmonic* none

Hereditary Angioedema

Problem with C1 estuaries inhibitor (C1-INH). Tx: FFP C2 and C4 low, C1q normal, C1-INH activity decreased but levels can be normal or decreased. C1-INH inhibits Kallikrein, which if activated goes on to form bradykinin, which is a potent vasodilator. -increased bradykinin d/t C1 inhibitor that cannot inhibit kallikrien.

SCID (X-linked recessive)

The mc form of SCID. M>F -defect in the common gamma chain encoded by the *gene IL-2 receptor gamma* located on the X chromosome. this IL receptor plays plays an important role in the development and differentiation of B and T cells. and its wide spread effects can cause complete failure of the immune system to develop and function. -deficiency of B and T cells. -failure of the thymus to develop - *chronic recurrent diarrhea* -PNA -Thrush -failure to thrive Labs: WBCs <3k; decreased IgG, M and A Rx: bone marrow transplant. *Picmonic:* Wolverine in front of skid marks with t and B balls and microbes falling out. with the chained IL-2 and bone train plant.

Patau Syndrome

Trisomy 13 defect in fusion of the precordial mesoderm - lead to midline defects -*holoprosencephaly* brain fails to develop into 2 hemispheres. -cyclops babies -microcephaly -polydactyly -*cutis aplasia* absence of epidermis over the skull -*midline cleft palate/lip* -micropthalmia (1 or both eyes small) -severe mental retardation -*rocker bottom feet* seen also in Edwards -polydactyly -*VSD* *Picmonic:* kid in rocking chair with friday the thirteenth on tricycle, halo brain, small eyes, parrot, vase with hole and cracked plate. *Picmonic* halo on child with paddles. Has small pea eyes with rocker bottom feet on cystic kidney. with friday the 13th man on tricycle with read tarred book with small head and poly the parrot. between is VSD vase and cracked plate.

Edward's Syndrome

Trisomy 18 (more common in females) -*clenched hand (2nd over 3rd, 5th over 4th)* -*rocker bottom feet* -*micrognathia* small jaw -cardiac defects - VSD -horseshoe kidney -*malrotation of gut* and *omphalocele* -prominent occiput -Meckels diverticulum -95% die within first year of life. *Picmonic:* Edward scissor hands, cutting micrognathia bush, with omphalocele fish bubble, octopus, and micky diving in. foreground = clenched fists with overlapping fingers *picmonic* Edward scissor hands with voting stand, read tarred grandma, hedge bush with small chin, micky diving into the omphalocele. octopus on occpitu, horseshoe kidney and rotational malate.

Down Syndrome

Trisomy 21 -*hypotonia* -protruding tongue -flat nasal bridge -*epicanthal folds* -single palmar crease - *simian crease* -congenital heart defects - septum primum ASD, endocardial cushion defects, -*sandal toe deformity* -upslanting palpebral fissures -*hirschprungs* -*duodenal atresia* -increased *Alzheimers* increased acute lymphoblastic *Leukemia* *Picmonic* the 21 year old on tricycle getting into eye club with ALL DJ, heart cushion with duodenal tree and hircshprung stomach with simian monkey.

Von Hippel Lindau

VHL Chromosome 3 -*hemnagioblastoma* - medulla, retina and cerebellum. benign vascular tumor -*cysts* throughout kidney, pancreas and liver -*B/L clear cell carcinoma* -can cause pheo's -*B/L retinal angiomas* *Picmonic* - he man chrome blasting medusa with organ cyst balloons. fiats with owl on 3 tree. gnome with B/L girl kidneys.

X-linked Agammaglobulinemia aka *Bruton's* agammaglobulinemia

X-linked agammaglobulinemia characterized by severe hypogammaglobulinemia and decrease of mature B cells with normal T-cell number and function. *SxS appear earlier in life, 6-12 months, versus CVID* Defect in *BTK, a tyrosine kinase gene*, involved in B-cell maturation. *X-linked recessive* B-cell development does not progress beyond pure B-cell stage. SxS: -3-6 months (when material ABs die off) -severe recurrent sinopulmonary and GI infections. Labs: -normal T-cells -decreased B cells - and all Ig decreased; *decreased IgG, IgA, IgE and IgM.* -scanty/absent lymph nodes and tonsils. *Picmonic* - granny button with tire portal that converts B-babies to adult B-balls with X-linked recessive suit. All Ig's on time out.

Rett Syndrome

X-linked dominant disorder seen almost exclusively in girls (affected males die in utero or shortly after birth). *MeCP2* mutation Symptoms usually become apparent around ages 1-4, including regression characterized by loss of development, loss of verbal abilities, intellectual disability, ataxia, *stereotyped hand-wringing.* *Picmonic:* none

Adrenoleukodystrophy

X-linked genetic disorder affects *males* disrupts metabolism of *very-long cain FA's* excessive build-up in NS, adrenal gland and testes long term disease that can lead to come/death and adrenal gland crisis. defect in gene ABCD1 - which codes for the VLCFA transporter. *Picmonic* none

Adrenoleukodystrophy

X-linked genetic disorder typically affecting males. disrupts metabolism of very long chain fatty acids - build up in NS (can appear as symmetric calcified plaques in all lobes of the brain, adrenal glands and testis. progressive disease that can lead to long term coma/death and adrenal gland crisis. *Picmonic* none

Menke Disease

X-linked recessive CT disease cause by *impaired copper absorption* and transport d/t defective Menke protein (ATP7A). leads to *decrease of lysyl oxidase*, for which *copper is a necessary cofactor*. SxS: brittle, kinky hair, growth retardation and hypotonia *Picmonic* none d/t decrease in cross-linking of collage fibers whereas Ehlers is d/t defect in proteolytic processing and cleavage of terminal collage ends.

Becker Muscular Dystrophy

X-linked recessive deletion of dystrophin gene on chromosome 21. -onset 5-15 y/o -middle age of onset. milder weakness compared to Duchenne comorbidity *cardiomyopathy.* -death by 40-50 y/o from heart failure.

Kallman Syndrome

X-linked recessive. Failure of migration of fetal GnRH and olfactory neurons. 1. *hypogonadotropic hypogonadism.* FGFR-1 or KAL-1 genes males = micropenis, undescended testes, no puberty. Females = no puberty development. 2. *Anosmia* 3. decreased FSH and LH levels. 4. can also be associated with hearing loss *Picmonic* super Kallman in phone booth with firefighter frog, GnRH gopher and nose on fire.

Charcot-Marie-Tooth disease aka Hereditary motor and sensory neuropathy

a group of progressive hereditary nerve disorders related to the defective production of proteins involved in the structure and function of peripheral nerves or the *myelin sheath*. -AD inheritance. -associated foot deformities *pes cavus* -LE weakness -sensory deficits -normal cognitive function *Picmonic*: none

Kawasaki disease

a type of Vasculitis fever > 5 days plus >3 of the following -bilateral non-exudate *conjunctivitis* -*mucositis* (injected or fissured lips, red throat or *strawberry tongue.* -*cervical LAD (lymphadenopathy)*, at least one lymph node >1.5 cm diameter. -*sandpaper rash* - on palms or soles -*edema* and erythema of the extremities Tx: *ASA* and IVIg complication: coronary artery *aneurysm* *Picmonic* asian child on motorcycle with lymph lime, strawberry tongue, edamame, fever beaver, necrosis crow, eyeball con with ASA against heart.

Zellweger Syndrome

aka *cerebrohepatorenal disease* congenital disorder characterized by a reduction or absence of functional peroxisomes SxS: impaired neuronal migration, neuronal positioning and brain development. Craniofacial abnormalities, hepatomegaly and renal cysts *Picmonic* none

Hartnup Disease

aka Pellagra-Like dermatosis *AR* defective neutral aa transporter on renal and intestinal epithelial cells. the most important aa affected is *tryptophan* which means decreased niacin, serotonin and melatonin. decreased niacin = decreased NAD+ for redox reactions. leads to pellagra like symptoms increased neural aa's in the urine. Tx: increased protein in diet and niacin supplementation. *Picmonic* hard hat nut on the defective bridge to the stomach and kidney. there is a recessive chocolate with a toe fan in the river with the pelican. the neutral characters cannot cross the bridge.

Diamond-Blackfan Anemia

aka congenital hypoplastic anemia -a disorder of the bone marrow, *increased apoptosis of the erythroid progenitor cells.* -*macrocytic anemia* decreased reticulocyte count, congenital anomalies (microcephaly, ptossi, hypertelarism, malformed/abscent thumbs) -increased Hb-F levels. -Rx - steroids *Picmonic:* none

Wilms tumor

aka nephroblastoma -typically seen in *children* -does not cross midline but can be bilateral malignant tumor of the metanephric blastema aka *metanephros* -WT1 gene there is familial or sporadic. associated with: 1. WAGR syndrome, Denys-Drash syndrome, and Beckwith-widemann syndrome. Presentation: *Large flank mass with hematuria. HTN d/t renin secretion.* *Picmonic*: Wonky Willy Wonka, children in chemo head wraps, fever beaver, hematuria and unilateral flank mass.

Werdnig-Hoffman Syndrome

aka spinal muscular atrophy type I evident at birth or within first few months. degeneration of *anterior horn cells+ and *CN nuclei* d/t mutation of SMN1 gene -*floppy baby* -breathing and swallowing problems -tongue fasciculations -absent DTR's -sits in frog-leg position

Von Recklinghausen Syndrome (NFT type 1)

also NF1: autosomal dominant. *chromosome 17* -cafe-au-lait spots (>6, >5mm in diameter) -*neurofibroma (mass derived from schwann cells)* -*lisch nodules* (raised pigmented bumps aka hamartomas on iris) -*freckling in armpits and groin* -Optic glioma -scoliosis -learning disability - ADHD. -*hamartoma* (disorganized growth of tissues in their native location) -Pheo increased risk of developing brain tumors and leukemias. *Picmonic*: fabio with shark, lisch fish, glowing eye and cafe cow.

Noonan Syndrome

autosomal dominant "The male tumors" -chromosome 12 -*dysmorphic facial features* - misaligned teeth, micrognathia, neck webbing / nuchal folds -*cardiac abnormalities pulmonary valve stenosis (60%)*, hypertrophic cardiomyopathy. -short stature -chest: pectus excavatum and/or carniatum -cryptoorchidism. -coagulopathy -face becomes increasingly triangular. -*mental retardation in 25%* *pimonic* none

HNPCC or Lynch syndrome

autosomal dominant cancer syndrome caused by inherited mutations in genes from *DNA mismatch repair enzymes.* -increased risk of colorectal carcinoma (proximal colon is always involved) -also increased risk of cancer in the stomach, small intestine, liver, gallbladder ducts, brain, upper urinary tract and skin. -women are at higher risk cancers of the ovaries and endometrium. *Picmonic* the lunch lady

Li Fraumeni Syndrome

autosomal dominant mutation of TP53 - a gene tht codes for the tumor suppressor gene p53. Patients inherit one bad gene for this and then need a somatic mutation of the other. cancer presents at a younger age, and includes *Sarcoma, breast, leukemia, adrenal gland* also know as the *SBLA* cancer. *Process in cell cycle* p53 induces p21, which inhibits CDKs - hypophosphorylated (activation) of Rb. hypophosphorylated Rb binds to and inactivates transcription factor E2F - inhibition of G1-S progression. Mutations in these genes results in unrestrained cell division. *Picmonic* none

Homocystinuria

autosomal recessive -multiple causes, but one is deficiency of cystathionine synthase. -Marfanoid body habitus WITHOUT the arachnodactyly. -*intellectual disability* -*thrombosis (CVA)* -*DOWNward lense dislocation* -*megaloblastic anemia* -*fair complexion* -scoliosis -cardioac abnormalities including aortic dilation that is not seen in marfans. (bolded above sets it apart from Marfans) pectus defomrity, tall stature, arachnodactyly, scoliosis, skin hyperelasticity. Dx: increased homocysteine, increased methianine in urine and plasma. or a positive urinary nitroprusside test. Tx: vit B6, folate, Vit B12, and decrease homocysteine. see biochem notecards

Kluver Bucy Syndrome

bilateral amygdala lesions. Patients with acute *HSV-1 encephalitis* can develop this. Associated with hyperorality, hyper sexuality, and patients have disinhibited behavior. *Picmonic*: bus driver with PDA hikers and amygdala doll.

Selective IgA Deficiency

can be familial or acquired. Higher incidence in caucasian pt's. -most patients are asymptomatic. -resp, mouth, GI, urogenital tract infections. -increased Giardia Lamblia infections -increase in atopic and autoimmune diseases -increased risk of celiacs Lab = extremely decreased IgA d/t impaired isotope switching *Serum ABs to IgA found in 40% of patients. if these patients get blood transfusion or tetanus Ig, they can develop severe anaphylactic / transfusion reactions.* *picmonic*: apple goblin with celiac, bowles and lamb with diarrhea

Beckwith-Wiedmann Syndrome

classified as an overgrowth syndrome - *WT2 gene mutation* *common features* -*Macrosomia* but growth tends to slow around 8 y/o -macroglossia - speech problems -*hemihyperplasia* - uneven growth of specific parts of the body - *midline abdominal wall defects* such as omphalocele, umbilical hernia, diastasis recti. -visceromegaly -hypoglycemia in infancy -increased risk of CA: hepatoblastomas and *Wilms tumor* -*ear creases or ear pits* *Picmonic* none

Amyotrophic Lateral Sclerosis

combined UMN and LMN deficit. *defect in superoxide dismutase 1* -assymetric limb weakness -fasciculations -spasticity fatal 3-5 years after diagnosis d/t respiratory failure. there is no cognitive decline in this disease *picmonic* - Lou Gehrig with fast pickle, spaz tic, lungs with the no brain sign, moderate exercise guy with Riluzole Tx.

Angelman syndrome

d/t imprinted father's gene and mutated mother's gene. imprinted genes are silenced genes, meaning they are not expressed and can be a normal phenomena. all humans have two sets of genes, one from mom and other from dad. usually imprinting is not an issue, as the other gene is expressing the given trait. however, if there is a mutation in the non imprinted allele then there will no longer be a functional copy. SxS -chromosome deletion on long arm of chrome 15; 15q -*happy puppet syndrome*, constantly laughing and excitable -ataxia -mental retardation -seizure -EEG shows large amplitude low spike waves. -blond hair and pale-blue, deep set eyes. *picmonic* angel man with daughter in her puppet quincañera

Acute Intermittent porphyria

decreased *Porphobilinogen deaminase* accumulated substances: serum porphobilinogen, serum Delta-ALA, coporphobilinogen. SxS: 5 P's - painful abdomen, port-wine colored urine (after exposure to light), polyneuropathy, psychological disturbances, precipitated by P450 inducing drugs. -AD -Tx: glucose and heme *Picmonic*purple mitten fairy in the woods with psycho man with port wine cooled urine.

Porphyria cutanea tarda

defect in *uroporphyrinogen decarboxylase*. accumulates substances: uroporphyrin (increase in serum leads to tea colored urine). blistering cutaneous photosensitivity -worsened by OCP and alcohol 20% AD, 80% sporadic, and most associated with *Hep C* *Picmonic* tarred and poor fairy with blisters near the obese Hep C cat.

Chédiak-Higashi syndrome

defect in lysosomal trafficking regulator gene (LYST). -Microtibule dysfunction in the phagosome-lysosome fusion. -AR -recurrent pyognic infections by staph and strep -*Partial albinism* -progressive neuropathy and neurdegeneration infiltrative lymphohistiocytosis. -*Giant granules in granulocytes and platelets. -pancytopenia -mild coagulation defects *Picmonic* cheetah hitchhiker to stripper pie. lyst stop light with microtubule broken truck with granny handing out plates and granules. albino owl and cat.

Williams syndrome

defect in the *elastin gene on chromosome 7*. -*elvin facies* short palpebral fissure, flat nasal bridge, round cheeks. -vascular anomalies: *supravalvular aortic stenosis* - HTN. -Intellectual disability -Sensitivity to sound and sleep problems. -Endocrine: short stature, *increased calcium*, DM, hypothyroid -*cocktail party personality*. Extreme friendliness to strangers, well developed verbal skills, and social personality. -CT abnormalities - hoarse voice and hernias. *Picmonic:* William the elf, gambling and reading from the tarred book to strangers, such as calcium cow and daisy viking with heart pulling at elastic pants.

Xeroderma Pigmentosa

defective nucleotide excision repair. this prevents repair of pyrimidine dimers d/t UV light exposure. -freckling -corneal ulcerations and red eyes -increased risk for basal cell carcinoma and other skin carcinomas -*Picmonic* none

Lesch-Nyhan Syndrome

defective purine salvage d/t *absent HGPRT*, which converts hypoxanthine to IMP and guanine to GMP. results in *excess uric acid production* and de novo purine synthesis. -X-linked recessive. -SxS: -Intellectual disability -*self-multilation, aggression* -hyperuricemia *(orange sand or sodium urate crystals in diaper)* gout and dystonia. *HGPRT or He's got purine recovery difficulties* *Picmonic* ninja on leash with preppy boy. unicorn gout with lemon, read tarred book.

CHARGE associations

group of associated malformations that occur sporadically. C - colobomas (absence or defect of ocular tissue) usually of the retina and vision is impaired. H - heart defects, mc tetralogy of Fallot. A - atresia of the nasal Choanae R - retardation of growth and cognition. G - genital anomalies - genital hypoplasia E - ear anomalies - cup shaped ears and hearing loss Diagnosis is clinical *no picmonic*

Chronic Granulomatous Disease

group of disorders characterized by defective neutrophil oxidative metabolism as a result of defects in the multicomponent reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase system = results in severely impaired intracellular killing of catalase-positive bacteria and some fungal pathogens. mutations affecting *NADPH oxidase*. most are X-linked recessive. -recurrent cutaneous and sinopulmonary infections. particularly susceptible to catalase positive bugs (S aureus, serratia, aspergillus) -Dx: neutrophil function testing: 1. *dihydrorhodamine 123 test* (phagocytic cells convert DHR to rhodamine which is fluorescent, then perform flow cytometry; + means no immunofluorescence) 2. *nitrolene tetrazolium test* (+ means DOES turn blue, so with CGD it is negative) *Picmoinc*: granny on lama with cats in the packman's, decreased H2O2 and Ox daisy with nicotine.

CVID (common variable immune deficiency)

heterogeneous group of disorders characterized by hypogammaglobulinemia. *Not inherited, therefore appear more in 4th and 5th decades of life* Bruton's appears 6-12 months and is hereditary. most patients have normal number of B and T cell but variable degrees of T-cell dysfunction. Can be inherited, sporadic, or acquired. *B-cells are not defective, rather they don't have the proper T-cell help* -respiratory infections, asthama, bronchiectasis *Giardia infections* -coexistant pernicious anemia Normal B-cells in the peripheral blood are present but they are not able to differentiate into AB secreting cells. *decreased plasma cells and decreased immunoglobulins* *Picmonic*: dad vacuuming with two baby B-calls, vacuuming up Ig's with decreased plasma cells and auto in moon.

Familial Adenomatous Polyposis

inherited mutation of the APC gene, which is a tumor suppressor gene on chromosome 5. autosomal dominant -100's to 1000's of colonic polyps -colon and rectum are removed prophylactically otherwise there is a 100% risk of colon cancer by the age of 40. sigmoidoscopy starts at 8-12 y/o

Hemolytic Uremic Syndrome

m.c. in toddlers. caused by *Shiga toxin* from *E. coli O157:H7* or *shigella* -acute diarrheal illness that release shigga toxin that then injure endothelium that causes platelet aggregation. that leads to shearing of RBC's as they pass by = *helmet cells on* 1. hemolytic anemia 2. thrombocytopenia 3. acute renal failure Antecedant diarrheal illness (can be bloody too) *Picmonic* - uremic rainbow, with acute angle toilet and small child ripping up colon. then helped cells, etc for triad. supportive care with dialysis machine.

Neuroblastoma

m.c. tumor of the adrenal medulla in children, usually <4 y/o. originates from *neural crest cells.* occurs anywhere along the sympathetic chain. most common presentation is abdominal distention and *firm irregular mass* that can *cross the midline* (Vs. Wilms/nephrolbastoma which is smooth and unilateral/does not cross midline). less likely to develop HTN than pheo. -can present with *opsoclonus-myoclonus syndrome* (dancing eyes dancing feet) -increased HVA and VMA in urine -*Homer-Wright rosettes* -bombesin and NSE positive -overexertion of N-myc -classified as APUD tumor *picmonic* none

VACTERL

mesodermal defects that are commonly found together but no known association exists for these congenital defects: -V: Vertebral defects -A: Anal atresia -C: Cardiac defects - mainly VSD -TE: tracheo-esophageal fistula -R:Renal defects -L: limb defects (muscle and bone) to diagnose this you need to check for each of the others. X-ray: vertebral, limb defects and nasogastric tub to view the TE fistula. Echo for the heart. US for the kidneys. and PE for the anal atresia. *Picmonic* none

Denys-Drash syndrome

mutation in the *WT1* gene (Wilms tumor suppressor gene) 1. nephropathy (diffuse glomerulosclerosis. 2. Wilms tumor (90% chance) unilatreal/bilateral 3. Gonadal dysgenesis (ambiguous external genitalia. affected females dually have normal genitalia and thus only have renal problems. males will have undescended testes and will be infertile. No picmonic

McCune-Albright Syndrome

not inherited, random mutations in GNAS gene in very early development. defects in GPCR cAMP-kinase function in affected tissues - autonomous tissue activity. basically defect in G-protein signaling. 3 P's 1. *precocious puberty* menstrual bleeding by age two 2. *pigmentation* cafe-au-lait spots 3. *polyostotic fibrous dysplasia* normal bone and tissue replaced with fibrous tissue. there is an asymmetric growth of bones Lethal if mutation occurs before fertilization, but survivable if occurs post fertilization aka mosaicism. *Picmonic* none

Kartagener Syndrome

primary ciliary dyskinesias -immotile cilia d/t a dyenin arm defect classic triad: 1. recurrent sinus and pulmonary infections. 2. bronchiectasis. 3. +/- situs inversus can also lead to infertility b/c of cilia on sperm and in fallopian tubes - *increased risk of exotic pregnancy* *Picmonic* none

Hereditary orotic aciduria

rare autosomal recessive disorder of de novo *pyrimidine synthesis* that results in physical and mental retardation (low height/weight and not meeting developmental milestones), *megaloblastic anemia* (high mean corpuscular volume and low reticulocyte count) and elevated *urinary orotic acid levels*. increased urinary orotic acid levels may also be seen in ornithine transcarbamylase deficiency; however, patients with OTC deficiency have hyperammonemic encephalopathy within the first few weeks of life due to impaired urea synthesis. Hereditary orotic aciduria occurs due to a defect in *uridine-5-monophosphate (UMP) synthase*, a polypeptide with 2 enzymatic domains, rotate phosphoribosyltransferase and OMP decarboxylase, that catalyze the final conversion of *orotic acid to UMP*. paired conversion of orotic acid to UMP results in the excretion of large amounts of orotic acid in the urine and the clinical features explained above. uridine supplementation can bypass the enzymatic defect and improve symptoms as uridine is converted to UMP via nucleoside kinase. *Picmonic* lemons and urinal with UMPire.

Felty Syndrome

rheumatoid and neutropenia and splenomegaly. more prone to infections but unknown cause. can have anemia, vasculitis and discoloration of the LE.

Caplan Syndrome

rheumatoid arthritis, pneumoconiosis, intrapulmonary nodules

Cri-du-chat syndrome

short arm *5p deletion* -*Cat like cry*- underdeveloped larynx. -intellectual disability -microcephaly -*difficulty sucking and swallowing* -orbital *hypertelarism*: increased distance between eyes -wide flat nasal bridge -hypotonia -high arched palate -cardiac abnormalities *Picmonic* crying cat with paint palate and cut off fifth little finger, read tarred book and defective heart. next to weirdly faced girl and small head doll.

MEN 1

the 3 P's *AD* germline mutations in menin which is a tumor supressor gene (MEN1) on chromosome *11q13* 1. *Parathyroid* hyperplasia/adenoma 2. *pancreatic* neuroendocrone tumors - gastrinomas, insulinomas, VIPomas. 3. *pituitary* adenoma, mc is prolactinoma *Picmonic* man on stage with minions, parathyroid gland, balls on dog and tumor guy eating the pancreas.

Tetralogy of Fallot

the most common *cyanotic* heart defect. 1. RVOT obstruction (pulmonary stenosis with atresia). *the degree of RVOT determines clinical presentation. 2. RVH 3. Overriding aorta 4. VSD crying, feeding, hyperventilation - TET spell from dramatic infundibular spasm. Rx for get spell - knee to chest causes increased SVR and decreased right to left shunt. -murmur, fixed single S2 with diastolic rumble at the apex. *Sketchy:* four manga girls

Behçet Syndrome

triad -*recurrent apthous ulcers* (painful superficial ulcerations of the oral mucosa caused by stress that resolve spontaneously. characterized by a grayish base surrounded by erythema -*genital ulcers* -*uveitis* d/t *immune complex vasculitis* can be seen post viral infection but etiology unknown *Picmonic* none