NU665 Final exam

Frameshift mutation

-Insertion and deletions - INDELS -Insertions and deletions in the codons can change the gene message so that it cannot be coded or it cannot be coded correctly - frameshift mutation -Tay-Sachs, many types of cancers, Crohn disease

Primary care for children with congenital and inherited disorders

-Many will be covered under CYSHCN - children and youth with special health care needs - as they are at an increased risk of chronic physical, developmental, behavioral, or emotional conditions and may require added health-related services -May require an array of subspecialty services in the hospital as well as in the community and at school -PCP - assists families with upfront identification of specialists, refers when services are needed, and maintains ongoing communication so that recommendations can be followed and reviewed with the child/family -AAP committee on genetics developed specific health supervision guidelines that highlight the most important management guidelines for these children - needs by age, cautions, syndrome-specific growth charts, vaccine considerations, and current/emerging research findings

Government resources for CSHCN

-Medicaid - many rely on this as their sole health care coverage -SSI - provides financial help with care costs if the child has severe functional limitations caused by a physical and/or cognitive impairment likely to last longer than a year or to result in the child's death -Durable Medical equipment (DME) and reimbursement - essential to fill out paperwork properly

Fragile X syndrome

-Most common inherited disorder of MR 1. Clinical findings - prominent forehead, long narrow face, prominent jaw, high-arched palate/dental crowding, protuberant ears develop late childhood/early adolescence, feeding problems/GER, strabismus, refractive errors (hyperopia, astigmatism), nystagmus, ptosis, recurrent/chronic OM, seizures, short stature, macroorchidism (puberty), connective tissue dysplasia (velvet-like skin, joint hypermobility especially fingers), pes planus, congenital hip dislocation, clubfoot, scoliosis, OSA, possible in girls 2. Neurodevelopmental cues - intellectual disability, language delays, behavioral problems (anxiety, attention, aggression), stereopathies, such as hand flapping, autism spectrum disorder 3. Any male child with developmental delay, borderline intellectual ability, or MR should be tested as early physical recognition is difficult as clinical phenotype (males) can be subtle prior to puberty 4. Cognitive deficits can be moderate to severe 5. Often experience delayed toilet training, enuresis 6. Hypersensitivity to sensory stimuli is common. Avoid excessive stimulation (crowds, loud noises); provide earphones 7. Monitor for behavior problems, such as ADHD, emotional lability, irritability, and temper tantrums 8. Increased risk for seizure activity, decreasing in adolescence 9. Language delay is common, decreasing at adolescence 10. Infants may have congenital hip dysplasia and/or clubfoot, feeding difficulties, GER, hypotonia, and irritability 11. Increased incidence of recurrent/chronic OM, sinusitis 12. Audiologic evaluation annual for conductive hearing loss 13. Orthopedic referral for connective tissue dysplasia issues - pes planus, hypermobile joints, scoliosis 14. Ophthalmologic evaluation annually for strabismus, refractive errors 15. Increased risk of inguinal hernias 16. Macro-orchidism begins - 9 years of age; adolescent growth spurt is less 17. Increased risk for autism, HTN, mitral valve prolapse 18. Females have wider phenotypic variability - premature ovarian failure (menopause) is common

National Organizations and Resources

-Most national organizations provide written materials parents and children can easily understand about the cause, management and treatment of the particular disease in question -These materials can help parents explain their child's condition to teachers and others -These organizations can guide them to support groups with families and children with similar diseases -They can help them access services that benefit their children - camps, sports, learning about legal rights, special adaptive equipment -PCP - National organization for rare disorders assists providers and parents and offers information about conditions or disease processes

Autosomal recessive*

-This type of single gene disorder requires inheritance of two copies of a mutated gene (one from each parent) located on one of the autosomal chromosomes (1-22) -Offspring who inherit only one abnormal gene are carriers - they can pass it on to their children but are unaffected -For offspring of parents who both carry an AR mutation, there is a 25% chance of inheriting the mutation from both parents, thus developing the disorder, a 50% chance of inheriting one copy and becoming a carrier, and 25% chance of not inheriting either mutation -Cystic fibrosis, albinism, thalassemia, and sickle cell anemia -The clinician reviewing a child's history should consider AR inheritance when a specific phenotype affects multiple siblings and both sexes are affected, the phenotype is often not present generation after generation

Genetics referral

-When there is a positive history for an inherited disorder for which the child is at risk, physical findings/dysmorphic features on physical exam consistent with a known syndrome, known inborn errors of metabolism, and/or noted developmental, growth, and/or structural abnormalities -They can order appropriate tests and give information with expertise in diagnosis, understanding inheritance patterns and recurrence risk, genetic testing, nuanced mechanisms of congenital and inherited disorders, and evolution of clinical manifestations across the lifespan -PCP is first line to send for genetic referral; the one who decides who needs attention and further testing/retesting, monitoring, and referral

Creating an emergency plan

-A set of instructions that outlines when, where, who, and how to contact emergency personnel should their child need emergent care -This can be in letter form for the family to use when needed -Should identify the child's diagnosis, clinical findings/status, current medications, allergies, and immunizations -Also need to highlight common presenting problems/findings with specific management strategies and professional pediatric and subspecialty contact information, especially for emergency care providers who may have limited knowledge regarding congenital and/or inherited disorders -An illness or surgical procedure may become life-threatening if certain precautions are not attended to

Mitochondrial disorders

-A small amount of genetic material is found in the mitochondria located in the cytoplasm, outside the nucleus -Contains 37 genes -Caused by mutations in mtDNA (nonchromosomal DNA) and are progressive disorders affecting the brain and muscles -Characterized by maternal transmission -Leber hereditary optic neuropathy, Leigh syndrome, nonsyndromic deafness, mitochrondrial encephalomyopathy, lactic acidosis, and stroke-like episodes

Single-gene disorders

-Aka monogenetic disorders -Occur when the mutation affects one gene -The mutation may be present on one or both chromosomes, associated with one of three different Mendelian patterns of inheritance - dominant (just one of the two alleles), recessive (both alleles), or X linked (confined to X chromosome) -Examples - sickle cell disease, thalassemia, neurofibromatosis, hemophilia, Duchenne MD, CF, fragile X syndrome, polycystic kidney disease, Marfan syndrome, and Tay-Sachs disease

Prader Willi syndrome

-Disorder related to genomic imprinting 1. Clinical findings - decreased fetal movement/position, FTT, short stature, central obesity, hypothalamic insufficiency, strabismus, myopia/hyperopia, sleep apnea, enamel hypoplasia, scoliosis 2. Neurodevelopmental cues - motor delays, poor coordination, language delays, mild intellectual disability, compulsive hyperphagia, behavioral phenotype - tantrums, stubborn, rigidity, skin picking, high pain tolerance, ADHD, compulsiveness 4. Use standard growth chart, paying close attention to weight-to-height; monitor for FTT and later short stature/central adiposity 5. Infants (first phase) - have significant hypotonia and early feeding problems; need for assisted feeding is nearly universal from birth to 6 months (tube feedings, feeding adaptations, Haberman nipples) 6. Children (second phase) - involves hyperphagia, with associated behavioral problems and obesity/obesity-related health concerns 7. Anticipate/help family plan for progression of behavioral issues; temper tantrums, obsessive behaviors, perseverant speech, skin picking (peri-anal, intertriginous folds), elopement 8. Hypogonadism (undescended testes, scrotal hypoplasia, small phallus/clitoris), trial of hCG is recommended for males, as anesthesia during infancy is high risk secondary to hypotonia 9. Premature (isolated) adrenarche is common 10. Global developmental delay: mild-moderate MR, increased risk of seizures (associated with fever) 11. Challenges for PCP: high pain threshold complicate timely assessment of illness/injury; children with PWS rarely vomit 12. Generalized hypothalamic insufficiency is characteristic, including growth hormone; GH is approved for young children with PWS older than two years of age, but newer, promising trials are exploring starting at 2 months of age (side effects are macrocephaly, adenotonsillar hypertrophy/OSA) 13. Reduced salivation leads to increased caries risk as early as 1 year of age; involve pediatric dentistry early; increase dental cleanings needed 14. Annual vision/hearing screen

Transition of care

-Barriers - the diversity of clinical conditions makes standardization difficult; no adult providers qualified to treat what were once considered childhood diseases; complex process across locations or levels of care -Factors influencing successful transitions - timing, patient transition perceptions, preparation for the transition, posttransition patient outcomes, barrier identification, and transitions facilitating the identification of these factors

IEP and 504 plans

-Children who do not meet criteria for an IEP may be eligible for 504 plan if they follow the curriculum without modification but require additional assistance in school settings such as physical, sensory, or mental support 1. 504 plan -Simple accommodations or minor changes; easier, faster, more flexible -Eligibility - based on identification of psychologic or physical disorder that limits a major life activity (learning or behavior) -Evaluation - compiled by the school from a variety of sources to confirm assumption; no money to cover evaluation or support; can occur without parental knowledge or participation -Provisions - extra time to complete assignments, a copy of notes, providing a quiet place to take tests, or assistive technologies; no legal requirements for what is included, for parent involvement, or mandated reevaluation 2. IEP -Needs a wide range of services or protections -More involved with mandated parental participation -Eligibility - meet criteria of qualified disability - ADHD not included - developmental delays, emotional disturbances, or SLD that affects learning or behavior -Evaluation - a complete evaluation compiled by a team of professionals including testing and information from a variety of sources; federally funded; must have written consent to perform -Provisions - it describes the child's learning problems, details services to be provided, sets annual goals, and defines how progress will be measured; changes made only in meeting and in collaboration with team; special provisions if suspected or expelled; reevaluation every 3 years

Technology dependence and medication

-Complex equipment such as home ventilators, enteral feeding pumps, wheelchairs, hospital beds, and nerve stimulations may be needed -Low-tech supplies may include respiratory or feeding tubing, special formulas or diets, urinary catheters, and ostomy bags -Ongoing family education is essential to ensure the safe and effective use or all devices and to make sure that families know how to fix common complications without seeking urgent care -Medications - be aware of polypharmacy - this leads to an increased risk of drug interactions and confusion about dosing and administration -Ongoing review of medication necessity and limiting the use of medication to compounding pharmacies; PCPs can help find compounding pharmacies as many of these kids require liquid medications and cannot swallow pills

Shared plan of care

-Comprehensive information compilation that, in partnership with the family, allows individualized care coordination 1. Determine needs and strengths of child/family - consider each family's situation and abilities, strengths and needs, medical conditions, psychosocial factors, child/family development, environmental issues; financial strengths and needs 2. Develop necessary partnerships - identify how providers, caregivers, and children work together; shared agreement on plan; account for family preferences and best practices 3. Develop a plan of care - identify roles and responsibilities of providers and families; include specific emergency care information; include fact sheets about rare conditions, legal documents about guardianship and/or health care decision making 4. Implement the plan of care - update the plan of care as needs change; evaluate and plan process at each encounter, assess progress towards goals and develop new goals as needed

Community and school-based services

-Early intervention, public school services, financial assistance programs, respite care services, and support groups -Many developmental, educational, and psychosocial support services are provided in school settings by government and community -Smaller school districts lack resources to provide these services

Early intervention

-From birth to age 3 -May include developmental, speech, physical, and occupational therapy, audiology, assistive medical technology, family training assistance, social work services and service coordination -PCPs should refer any child with suspected disabilities or developmental delays to EI services for evaluation and therapy -Services are generally free, but other services may be billed so referral to social work may be needed -After age 3, CSHCN transition to services through the public school system - IDEA and section 504 ensures free, appropriate education in the least restrictive environment possible for all children -Children with disabilities receive educational support in either general or special education classrooms, therapies including speech and OT, health care services needed during the school day, and emotional, behavioral, and psychologic services -PCPs should encourage parents of children receiving EI to contact their school before third birthday - they may be eligible for a 504 or IEP

Texting and e-mail

-HIPAA does not comment on messaging because the law was created before texting -As of 2013, all providers must have the ability to have secure healthcare communications with an encryption protection platform as part of their mobile device assuring that if there is a loss of a mobile device, the user can be disconnected from the system to avoid a data breach -PHI is not allowed to be stored on personal mobile devices if a personal mobile device is used on an open WIFI network -SMS are used to send appointment reminders, give educational messages, provide support to patients between visits, and track lab results -If text messaging is used by a provider evaluating a child's condition, it is important to ensure that the same information that would normally be asked in a telephone conversation is in the text message before giving any recommendations -Parents and families must agree to SMS messaging -Some practices have included requirements in their policy, such as encryption, passcode protection, registration of devices, or use of third-party secure messaging systems to avoid any breach of confidentiality -Emailing - can have same issues as texting; limit this type of communication to encrypted networks in which the device can be turned off if lost

Marfan syndrome

-Heritable, multisystem disorder of connective tissue 1. Clinical findings - phenotypic variability, including variable facial features - long, narrow face, downward slanting eyes, malar hypoplasia, and micrognathia; often tall for age, extremities disproportionally long in comparison with trunk; altered arm-span, height ratio; paucity of muscle mass/fat stores; aortic root dilation, aortic tear/rupture, aortic valve prolapse, regurgitation, tricuspid valve prolapsed, mitral valve prolapse/regurgitation; myopia, ectopia lentis (hallmark), retinal detachment, glaucoma, and early cataract formation; spontaneous pneumothorax, reduced pulmonary reserve, and OSA; skeletal issues, including pectus deformities, scoliosis, thoracic kyphosis, and protrusion acetabuli, pes planus, reduced mobility of elbow, increased laxity of other joints; stretch marks (lower back, inguinal, axillary regions), at risk for dural ectasia 2. Neurodevelopmental cues - usually within normal range 3. Syndrome specific growth chart peak growth velocity occurs up to 2 years earlier 4. Excessive linear growth of long (tubular) bones, typically taller than predicted for their family; altered arm-span to height ratio; bones of hands/fingers are elongated, but palm is normal, giving rise to positive thumb/wrist signs 5. Monitor for orthopedic conditions - joint laxity, protrusion acetabuli, scoliosis, thoracic kyphosis, pes planus; pectus abnormalities are common 6. Many clinical features are age dependent - ectopic lentis, aortic dilation, dural ectasia, protrusion acetabuli 7. Cardiac screening with echocardiogram continues throughout life - age on onset/rate of progression of aortic dilation is highly variable; B blockers are often prescribed; decongestants and psychostimulants should be used with caution 8. Ongoing BP monitoring (HTN) 9. Participation in contact/competitive sports, as well as isometric exercise is restricted; aerobic activities in moderation 10. Annual ophthalmology screen - myopia is common and progresses rapidly; ectopic lentis is hallmark feature; risk for retinal detachment, glaucoma, and early cataract formation 11. Dural ectasia often presents with postural hypotension/low pressure headaches 12. Increased risk of spontaneous pneumothorax, reduced pulmonary reserve, and sleep apnea 13. Stretch marks are common across lower back, inguinal and axillary regions 14. Hernias/recurrent hernias and incisional hernias are common

Neurofibromatosis

-Multisystem disorder primarily involving skin and nervous system 1. Two or more of the following are required -6 or more cafe-au-lait spots 5 mm prepuberty/15 mm postpuberty -2 or more neurofibromas or 1 plexiform neurofibroma -Axillary or inguinal freckling -Optic glioma -2 or more lisch nodules (iris hamartomas) -Associated osseous lesion -First degree relative with NF1 2. Learning, speech/language, and motor abilities vary 3. Autosomal dominant 4. Syndrome specific growth chart; macrocephaly and short stature are common; puberty growth spurt is reduced 5. Clinical features ae age-dependent; cafe-au-lait spots are usually the initial manifestation (birth-infancy); plexiform neurofibromas are usually congenital (face, trunk, extremities); axillary/inguinal skinfold freckling typically develops between 3-5; dermal neurofibromas typically develop prepubertally 6. Monitor for learning disabilities, with deficits in visual-spatial-perceptual skills and poor fine motor coordination leading to reading, spelling, and handwriting issues 7. Annual ophthalmology screen; optic glioma present with visual loss, severe proptosis, and/or hydrocephalus in young children; Lisch nodules typically develop in early adolescence (slit lamp exam) 8. Precocious puberty may occur, but need to rule out optic glioma as cause 9. Monitor BP (HTN) as a screen for renal artery stenosis, AS, and pheochromocytoma (adult) 10. Hypotonia and subtle neurological changes can affect gait/balance; caution for sports/activity 11. Monitor skeletal changes, including tibia dysplasia, scoliosis, increased risk for osteoporosis (adult) 12. Advise use of sunscreen after six months of age (sun will increase care au lait spots)

NORD

-National organization for rare disorders -Introduction for parents and caregivers to specific rare diseases -Gives synonyms, signs/symptoms, causes, affected populations, related disorders, diagnosis, therapies

Chromosome mutations

-Occur when even larger segments of a chromosome are deleted, duplicated, rearranged, or translocated in such a way that there is a resulting alteration of the DNA sequence, a modification of the gene dosage, or a complete absence of a gene or several genes -Down syndrome

Chromosome disorders

-Occur with changes in the number or structure of an entire chromosome, or large segments of it -Down syndrome (trisomy 21) is caused by an extra copy of chromosome 21 -Prader-Willi syndrome is caused by the absence of a group of genes on chromosome 15 -CML - translocation in which chromosome 9 and 22 are exchanged, resulting in a new abnormal gene -Also, cri-du-chat syndrome, Williams syndrome, DiGeorge syndrome -Can also involve sex chromosomes, such as Klinefelter syndrome (XXY), and Turner syndrome (XO; absence of an X) -Also mosaicism - which occurs when an altered chromosomal arrangement occurs in some cells but not in others within the same individual; clinical symptoms are milder and prognosis improves

Genetic counseling

-One specific aspect of the genetic specialist referral -Families need to consider genetic information when making health-related decisions that can affect their personal physical and reproductive health, as well as the lives of their child, other children, and extended family -Facilitates family's understanding of the diagnosis of concern, its course and management -Also, of how genetic/genomics influence the disorder -Help families choose a plan of action -Assists individuals and families to cope with a diagnosis, its prognosis, and the risk of recurrence

Costs and family burden

-Out-of-pocket costs and time spent caring for CSHCN can be significant and may lead to higher level care when care needs are not met -CSHCN are at risk for fragmented care, with poor team communication, crisis-driven health care, and insufficient caregiver support

Homecare and community services

-PCP in charge of arranging and recognizing the need for services

Tertiary care

-PCP makes sure family has documentation of child's condition, medications, etc. and knowledge of when to go to a higher level of care

Care coordination

-PCPs are ideal - when they act as care coordinators, this eases the burden on families, improves satisfaction, can help to improve health care outcomes and minimize health care expenditures -ideal because of their long-standing relationships with CHSCN and their ability to help families navigate the complicated and often intimidating health care system

Subspecialty care

-PCPs review notes and recommendations, looking for missing or duplicate items -May have an interdisciplinary clinic available

Legal issues

-Parents may face problems of how to provide for their child's care when they become old or die -These children may become dependent on the state and face complex care decisions -PCPs should encourage parents to seek legal advice to set up a power of attorney and medical decision-making expertise to make sure that their wishes for their child are carried out, including the appointment of a guardian -They should legally determine palliative care options and health care decision authority

Respite care

-Provide breaks from time to time -This can take place in homes or in institutional settings -Some states have assess to federal funds to help support these services for families

Multifactorial disorders

-Result form a combination of genetic and environmental factors -These disorders can cluster in families -Population based recurrence risk rather than a personal risk -Neural tube defects, such as spina bifida or anencephaly, also congenital heart defects, club foot, cleft lip/palate, pyloric stenosis, Hirschsprung disease, hip dysplasia and asthma

Klinefelter syndrome

-Sex chromosome disorder - XXY 1. Tall, with long arm plan, dental decay, delayed puberty, smal penis, cryptochidism (or small testes), gynecomastia, autoimmune disorders, skin striae, scoliosis, increased risk of malignancies, including male breast cancer 2. Neurodevelopmental cues - delayed expressive language, shy, withdrawn, immature for age, ADHD 3. Monitor growth and development, especially speech 4. Monitor for scoliosis 5. Annual thyroid screen 6. Caution - delayed puberty/gynecomastia/low testosterone; increased risk for autoimmune disorders, breast cancer

Family-centered care

-Shared-decision making is the basis for family-centered care with the ultimate goal of improve health and satisfaction

Point mutations

-Single base pair changes - substitutions, deletions, or insertions, occurring at the level of the nucleotide and capable of changing the function of a gene or gene product -Responsible for single gene disorders, such as sickle cell anemia, cystic fibrosis -Different from SNPs -Deletions - section of DNA is lost or deleted; example - 22.q11.2 deletion syndrome, Duchenne MD and neurofibromatosis -Insertions - extra base pairs are inserted; Duchenne MD, Charcot-Marie-Tooth Type 1A **Single gene disorders

Transition to adult care

-Starting at age 12 -Important for all children; very important for congenital and/or chronic physical and medical conditions

Patient-Centered HealthCare home plan

-The ideal care model for CSHCN -Provides accessible, continuous, comprehensive, coordinated, compassionate, culturally competent, and family centered care (parent knows their child best and notice when issues arise; you know they know something is wrong -shared decision making) 1. Plan of care - developed by PCP/designated care coordination, child and family; collaboration with other providers, agencies, and organizations involved with the care of the patient 2. Central record or database - pertinent medical information, including hospitalizations and specialty care; updated medical list; equipment, supplies, therapies with product information, suppliers, sizes 3. Care coordination - information-sharing among the child, family, and other providers; referrals to other health care providers, collaboration with agencies to obtain necessary services 4. Family support - support groups (online, national organization); parent-to-parent groups, social work, mental health services 5. Communication - information sharing among specialists and other professionals; families understanding of recommendations and treatment options, encouraging families to keep pertinent information and share this information with health care providers as needed

Genetics - ethical issues

-The national human genome research institute -A few issues include the rights to privacy and confidentiality, the rights to know, now know, the duty to warn, disclosure of incidental findings, and genetic discrimination -GINA - the genetic information nondiscrimination act - passed in 2008, with all aspects of the law in effect in November 2009 -This protects individuals from the misuse of genetic information in health insurance and employment and remove barriers to the use of genetic services -GINA does not affect healthcare -But under GINA, health insurers cannot use an individual's genetic information to set eligibility requirements, establish insurance premiums, or request certain genetic tests -Employers cannot request, require, or purchase genetic information about employee or family and they cannot use an individual's genetic information in decisions about job hiring, firing, assignments, or promotions -GINA cannot provide protection when a condition is already diagnosed or manifest, even if it is genetic -Does not apply to life, disability or long-term insurers -The type of information protected under GINA includes family health history, carrier testing, prenatal genetic testing, predictive testing, and other assessments of genes, mutations, or chromosomal changes -Groups exempt - military, veterans getting care through the veteran's administration, indian health services, and federal employees enrolled in the benefits program

Homozygous recessive

-The organism has two copies of the same allele for a gene -The organism is recessive if it carries two copies of the same recessive allele

Three-generation pedigree

-The pedigree is a valuable visible record of genetic links and health-related information -Should include at least three generations and is much more helpful in visual form -The health status of first, second, and third degree relatives of the individual's or child's family -The process of constructing a family pedigree should begin with the nuclear family, followed by added aunts and uncles, cousins, and grandparents -Records their date of birth or age, relevant symptoms, traits, or disorders, as well as the ages of diagnosis, and the ages and causes of death -Record miscarriages, stillbirths, infertility, and any children relinquished for adoption -Note missing information as missing

PCP as care coordinators

-These children require heath maintenance, illness prevention, and developmental surveillance -Traditional primary care needs - needed for routine vaccinations, common disease management, and family support and guidance -Collaboration among clinicians, case managers, family members, home care and school professionals, clinics, hospitals, and community-based services -Gatekeeper and care coordinator - collaboration for all needs -PCHH - patient-centered health home - ideal model for managing complex health care needs

Support groups and services

-These services are available through community-based services, parent training groups, and national organizations -Families should seek out services and get involved in educational, advocacy, and other activities to alleviate stress and caregiver fatigue

General guidelines for caring for children with congenital and/or inherited disorders

-They need support and guidance in coping with the new diagnosis and interpreting the myriad of information they have been receiving -PCPs need to be aware of regional resources so they can refer families -Genetic alliance - useful PCP/family resource containing a tool called disease InfoSearch; information on congenital or inherited disorders manifested in children along with links to education materials as well as advocacy and support organizations -The PCP must remain in contact with specialists caring for the child in order to coordinate local care and provide access to health, social, and spiritual support for the family -They should also advocate for parents who face significant challenges managing health care, daily care, and educational needs for their child -The PCP should be familiar with recurrence and occurrence risks for the child's disorder as it may have implications for siblings

X-linked recessive

-This disorder will occur in males -Males only have one X chromosome, so a single, abnormal, recessive allele on that X chromosome is enough to cause the disease -When the father is affected, none of his sons will be affected and all of his daughters will be carriers -If the mother is carrier, there is a 50% chance that each son will be affected -Daughters have a 50% chance of being a carrier like their mothers -Females can have these disorders, but it is rare -One should consider this type of inheritance when a specific phenotype is noted in males more often or more severely than females -Fabry disease, hemophilia A and B, G6PD deficiency, Duchenne MD

Autosomal dominant*

-This type of single gene disorder is characterized by the inheritance of a single copy of a mutated gene located on one of the autosomal chromosomes (1-22) -Passed on from one parent but results in an inherited disorder; the paired gene from the other parent is normal -The parent passing it on typically has the disorder -For the offspring, the chance of getting it is 50% -Without having the gene you cannot pass it on or have it -Huntingtons, Noonan syndrome, and neurofibromatosis type 1 -The clinician should consider AD inheritance when a specific phenotype appears in a family generation after generation, both sexes can be affected, and male-to-male transmission occurs

Health care issues for PCPs

-Time consuming with being on the phone, paperwork, reviewing medical records, and counseling parents -Many providers have discomfort in caring for these children because of a lack of knowledge of rare conditions or health care service requirements that may be beyond the scope of most PCPs -Poorly reimbursed

Edwards syndrome

-Trisomy 18 1. Severe MR and other genetic defects associated with AMA 2. Growth retardation; low set ears with prominent occiput and micrognathia; rocker-bottom feet and overlapping fingers; congenital heart defects, severe global developmental delays, CNS defects with hypertonia; feeding problems 3. Retardation of growth with severe FTT, microcephaly, low set ears, prominent occiput, micrognathia, heart murmur, clenched hands with overriding fingers and crossed thumb, small fingernails 4. Prenatal screening 5. Genetic counseling, psychosocial support, refer to cardiology, support nutritional needs, may require gastric feedings; prophylactic antibiotics to prevent subacute bacterial endocarditis, enroll in EI program for habilitative therapies; assist family with management of special needs (In home nursing), support organizations

Prenatal screening

-Typically offered to all women to screen for common syndromes and congenital anomalies, or to select omen who might be at a higher risk based on age, ancestral or ethnic background, or a specific family history of the disorder -Can do CVS or amniocentesis -Also, preimplantation testing is used to detect genetic changes in embryos created through assisted reproductive techniques before they are implanted

Newborn screening

-Used to identify inherited and congenital disorders that can benefit from early diagnosis and treatment -It involves individual and family education, mass screening for a select subset of congenital or inherited conditions, and short and long term follow-up plans for newborns who screen positive -34 core conditions and 26 secondary conditions for which baby should be screened

X-linked dominant

-When a disorder is classified this way, it means that a single abnormal gene on the X chromosome gives rise to the disease -If the father is affected and the mother is not, all of his female offspring will inherit the allele, but none of his male offspring, because daughters always inherit their father's X chromosome, whereas sons inherit their father's Y chromosome -If the mother is affected and the father is not, there is only a 50% chance that each daughter or son will inherit the disease causing allele and manifest the disorder, because mother's have two X chromosomes to pass on -Consider this when a specific phenotype affects both sexes in each generation, with slightly more females and the absence of male-to-male transmission -X-linked dominant disorders are often lethal in males -Rett syndrome, vitamin-D resistant rickets

Good documentation and patient visit

1. Be alert to a complaint or combination of complaints that are red flags for more serious illnesses - abdominal or chest pain, headache, syncope; note pertinent positives and negative history and physical findings relative to these complaints 2. Identify differential diagnoses and rule out serious or life-threatening illness first. Be sure to gather enough data to either rule in or out the diagnosis based on history, physical findings, and diagnostic studies; Rule outs are no longer acceptable by insurance providers. Providers must use medical terms such as RLQ pain rather than rule out appendicitis 3. Revisit an unresolved problem until it resolves. Reschedule a follow-up examination or use telephone or email contact with the family to determine if the complaint or illness resolved 4. Ensure there is a system in place to ensure that diagnostic studies were done, results received, and follow-up was done by the provider 5. Follow-up on referrals to other healthcare providers or agencies and document the recommendations or treatments from these referral sources 6. Document missed clinic appointments through chart audits, which should be a regular part of practice quality improvement. Look for such information omissions, whether problems identified in earlier visits were addressed at subsequent visits until resolved, and compliance with routine health maintenance screenings

Down syndrome

1. Clinical findings - short stature, brachycephaly, midface hypoplasia with flat nasal bridge, brushfield spots, epicanthal folds with upslanting palpebral fissures, small mouth with protruding tongue, myopia/cataracts, small ears/narrow canals, extra skin at nape of neck, lax joints (atlantoaxial instability), short broad hands/feet/digits, single palmar crease, clinodactyly, exaggerated space/plantar groove between great and second toes, congenital heart disease 2. At risk for leukemia, hypothyroidism, Alzheimer disease 3. Neurodevelopmental cues - intellectual/cognitive/disability/developmental delays, hearing loss, hypotonia (infant) 4. Careful review of newborn screen for hypothyroidism; annual and/or systematic screening for hypothyroidism 5. Careful review of newborn CCHD with ongoing cardiac evaluations 6. Monitoring growth using syndrome specific growth chart 7. Ongoing ophthalmologic exam for cataracts 8. Careful review of newborn hearing screen, following by otologic/hearing evaluation 9. Monitor for OSA 10. Increased risk of duodenal atresia 11. High risk of atlantoaxial instability - if signs of cervical myelopathy, obtain radiograph, refer to neurosurgery -Diagnosis includes an xray -May have changes in ambulation, ability to use upper extremities, complaints of neck pain, a new fixed head tilt, bowel or bladder dysfunction, or new unexplained weakness -No soccer, skiing, gymnastics, diving, judo, snowboarding; they can do noncontact sports 12. Monitor for neurological disorder - infantile spasms, seizures, moyamoya malformation 13. Systematic screening for celiac disease 14. Increased risk for leukemia

Triage questions

1. Description - tell me about the problem; what signs and symptoms are present 2. Duration - how long has the problem been present 3. Clinical changes - how has the child's behavior or activity level changed - eating, sleeping, playing, interaction with others 4. Appetite - has there been a change in eating or drinking 5. Elimination - have there been changes in bowel or bladder habits 6. Sleep pattern - has there been a change in the child's sleeping habits 7. Cause - what does the parent believe ma be contributing to the condition 8. Management - what has the parent done and the effect 9. Feelings - does the parent feel anxious about the current condition

Family history - genetics

1. Does anyone in the family have/had a birth defect? - if yes, get more info about nature of defect 2. Has anyone had a stillborn baby? A baby who died early? A baby who died unexpectedly? - to identify unrecognized syndrome; if early - could be inheritable metabolic disorder; distinguish SUID and SIDS 3. Is there any chance that you and your partner are blood-related? Is this pregnancy a product of incest? Any history of incest in your extended family? - risk for AR disorders; if yes - genetics counseling 4. Anyone in the family who see a HCP for a specific condition? - ask about hearing, vision, growth disorders; significant if early onset, two or more close relatives affected; genetic heart disease and genetic cancer risks are important - genetic consultation 5. Have you, your partner, or any siblings has three or more miscarriages? how about infertility issues? - may indicate a chromosome translocation; order a karyotype of mother or father or both; genetic syndrome may be considered due to not being able to maintaining a pregnancy 6. Anyone have learning problems, MR, behavioral disorders, delays? - look for multiple members affected and associated with dysmorphic features - genetics 7. What is your ethnic/geographic background? your partners? - certain ethnic and or population risk factors

Physical findings indicating inherited or congenital disorders

1. General -Short/tall stature -Body/limb disproportion -Failure to thrive or obesity 2. Craniofacial features -Unusual head shape/circumference/fontanels -Synophyrys (fused eyebrows) -Long eyelashes -Hyper/hypotelorism -Epicanthal folds -Up/down slanting and/or short palpebral fissures -Heterochromia, ptosis, cataract, glaucoma -Low nasal bridge -Abnormal ear position/shape/tags/pits -Short, long, or flattened philtrum -Malar flattening -Prominent metopic ridge -Bifid uvula, high arched/cleft palpate -Natal teeth/central incisor -Micrognathia 3. Hands/feet -Abnormal creases -Short/long digits -Prominent digital pads -Clinodactyly (incurved fingers) -Syndactyly (fused digits) -Polydactyly -Camptodactyly (bent/flexed) -Dysplastic nails 4. Hair/skin -Abnormal hair line or color -Increased numbers or anterior location of hair whorl -Hirsutism -Hypopigmented/hyperpigmented patches -Pigmented nevi 5. Neck -Short, webbing 6. Chest -Widely spaced or supernumerary nipples -Abnormal chest shape 7. Abdomen/genitalia -Redundant umbilicus -Shawl scrotum

Components of medical necessity letter

1. Identifying information about child - name, parent/guardian, insurance policy, DOB 2. Identifying information about provider - name and credentials, relationship to child, length of time caring for child 3. Date of last patient visit - and reason 4. Diagnoses 5. Pertinent medical history 6. Pertinent medical, developmental, or evaluative information 7. Why product/treatment/evaluation is medically necessary 8. Summary statement

Key indicators that affect treatment adherence in children and adolescents with acute illnesses or chronic conditions

1. Illness -Severity -Length and prognosis -Effect of illness on functional and social activities of daily living 2. Management -Complexity of treatment plan -Length of time for each treatment, how often, and for what length -Visibility of assistive equipment 3. Family -Support network and size of family -Financial resources; knowledge base and the understanding of illness; overall cognitive skills; communication style -Coping ability and skills; problem-solving skills -Family's belief system and spiritual base 4. Child or teen -Age -Cognitive, social, and emotional level of development; temperament -Peer group; coping ability 5. Healthcare provider and environment -Communication style of PCP with child, family, and other healthcare providers; belief in empowerment of parent and child/teen -Organization of clinic or office setting to the child, teen, and family friendly, need for adaptive modifications in their environment -Number of healthcare providers involved in the child's care; team member collaboration and partnership among themselves and with the family -Open and "blame-free" approach when adherence issues arise

Diagnostic genetic testing

1. Karyotype - used to identify and evaluate the size, shape, and number of chromosomes -Detects large deletions or duplications -Detects translocations 2. Fluorescence in situ hybridization (FISH) - used to locate and detect a specific area of a particular chromosome including subtle missing, additional or rearranged chromosomal material by labeling a known chromosome with fluorescent tags -Detects large deletions or duplications -Detects deletions or duplication in part of a chromosome 3. Chromosomal microarray - used to detect microdeletions or duplications in any of the chromosomes but not specific gene mutations -Detects large deletions or duplications -Detects deletions or duplication in part of a chromosome -Detects small deletions or duplications 4. Molecular testing - used to detect specific single gene mutations known to cause single gene disorders -Detects very small structure and sequence changes and single gene mutations

Nontraditional inheritance patterns

1. Mitochondrial inheritance - from mtDNA; mothers alone pass on this because only egg cells contribute mitochondria to the embryo -Can appear in every generation, affecting both sexes -Males are more severely affected -LHON, myoclonic epilepsy with ragged red fibers and MELAS 2. Codominant inheritance - two different alleles for a gene can be expressed and different combinations result in slightly different proteins -ABO blood group 3. Genomic imprinting - in some cases, only one copy of genes is expressed and the other copy is turned off or silenced during embryogenesis -Improper imprinting can result in a child having two active copies or two inactive copies -Prader-Willi syndrome, Angelman syndrome, Beckwith-Wiedemann and Russell-Silver syndromes 4. Uniparental disomy - when a child receives two copies of one chromosome, or a part of a chromosome, rom one parent and none from the other parent -The child will be homozygous fore every gene located on that chromosome -This can be from a random event during the formation of an embryo, or may happen in early fetal development -This usually has no affect on the child's health or development because most genes are not imprinted -Prader Willi, Angelman syndrome

Mutations vs polymorphisms

1. Mutations -An allele is a mutation when its genetic variability is found in less than 1% of a population; means a disease-causing variation -Point mutations, nucleotide repeat expansions, copy number variants, or chromosome mutations 2. Polymorphism -Refers to a normal variation, or one that does not directly cause disease -Type - single nucleotide polymorphism or SNP - used to study the genetic contribution to multifactorial disorders, such as cleft lip and palate, diabetes, heart disease, and cancer -Relevant because they help identify individuals at increased risk for multifactorial disease

Referral and consultations

1. Referrals -the patient will be assessed and managed by the provider referred to 2. Consultation -the PCP wishes to continue to manage the patient's care but seeks consultation about particular aspects of the care

Genetic red flags from history

1. Rule of Too/Two -Too many of something, individual is too tall, too short, too early, too young, too different, and so on -Two birth defects, two cancers, two in a family, or two generations involved

Common issues or concerns of children and families related to chronic illness care

1. The high cost of treatment and the potential need for financial assistance 2. Lack of, or barriers in, acquiring health care insurance 3. Navigating the healthcare system and required paperwork 4. The need for multiple healthcare providers and the frequent lack of coordination of services in providing continuity of care 5. Family lifestyle alterations that may be required to care for the child 6. Parents striving to normalize the child's condition and fitting into the family lifestyle 7. The effect of stress on emotional and psychological well-being of all the members of the family 8. The desire to be kept informed of their child's condition and progress 9. The amount of parental education and disease process, pharmacology, and other therapeutic treatments required for the at-home care of the child 10. How to best advocate for these children to access services through schools, state and community agencies, or special federally sponsored programs 11. Treatments or procedures that may be embarrassing, painful or time consuming 12. Unpredictability of the child's condition and the potential for complications, frequent medical visits, hospitalizations, and death 13. The developmental effect that chronic disease can have on a child, especially during adolescence and early adulthood (periods of increased vulnerability) 14. Acceptance by peers 15. Dealing with feelings (anger, sorrow) while attempting to cope with chronic illness 16. Problems of non-compliance

Differences between CSHCN (children with special health care needs) and without special needs

Table 7.1 -Mental health problems - ADD, mood disorders, autism, tic disorders -Atopic and rheumatic disorders - asthma, JRA, lupus -Endocrine and metabolic diseases - growth disorders, adrenal disorders, disorders of sex development, thyroid disorders, inborn errors of metabolism, DM, pituitary disorders -Congenital, genetic, or chromosomal defects - rare genetic diseases/syndrome -Premature and/or very low birth weight infants -Severe injuries or burns -Static or progressive neurologic and neuromuscular disorders - CP, global developmental delays, muscular dystrophy, spina bifida, seizure disorders -Respiratory disorders - cystic fibrosis -CV disorders - cardiac defects, long-term effects of acquired CV disease -GI disorders - IBD -Childhood cancers -Family psychosocial concerns - trauma/abuse, homelessness, undocumented immigration status, overwhelming needs with limited resources