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Master Boards Review -- Peds and Adult

Terms in this set (135)

Features:
Large for gestational age (LGA), hypoglycemia, omphalocele, macroglossia, hemihyperplasia, ear creases/pits, flamus nevus, organomegaly, cardiomegaly/cardiac anomalies.
4-10% risk for embryonal tumors:
US studies for hepatoblastoma and wilms tumors. Also at risk for rhabdomyosarcoma, adrenocortical carcinoma, neuroblastoma.
Genetics:
Chrom 11p15.5 with hypermethylation of H19, condition of abnormal maternal imprinting. Manifests only when the mutant gene is inherited from the mother. Maternal allele is not normally methylated, it is methylated in BWS and IGF2 expression is increased, H19 is silenced. Also KCNQ1 is usually methylated on maternal allele, but in BWS there is no methylation and silenced CDKN1C, which shuts off the brakes for growth
Inheritance and Recurrence Risks:
85% have no family history, 15% have AD inheritance pattern
1 - Methylation analysis: detect loss of methylation on IC2 of maternal chromosome (50% of cases) and gain of methylation on IC1 of mathernal chromosome (5% cases), very low RR
2 - Sequence analysis (if fhx of BWS, or last resort): Detects mutations in 5% of individuals w/ no fhx BWS and 40% in pt w/ fhx of BWS. If no fhx and CDKN1C mutation is detect, parents shoudl be tested for mutation. RR up to 50%.
3 - UPD analysis: paternal uniparental disomy of 11p15.5 (20% of cases), RR very low.
4 - Karyotype/FISH/microarray: Duplication, inversion or translocation of 11p15.5 (1% detection by Karyotype). Consider parental testing, RR can be as high as 50%.
Incidence overall: 1/600
Risk in 20s is about 1/1500, 30s rises, 40s levels out around 1/100. 50% of babies w/ DS born to mothers <35 years, average maternal age 31.5.
Cardiac defect: VSD, endocardial cushion defect
50% of babies with DS have one or more congenital abnormality: 40-60% of babies with DS have a heart defect and 12% have a gastrointestinal defect that may require surgery.
Life expectancy into 50s or 60s
Other features: hypothyroidism, leukemia.
Males typically infertile, but there are reports of fathering pregnancies. Theoretical chance for offspring w/ DS is 50% one affected parent, 66% two affected parents. Empiric data shows 30-50% risk.
95% have extra chromosome 21 (non-disjunction)
RR: age at previous trisomy <35 is age-related risk X3.5 for T21 and any aneuploidy is X1.3
RR: age at prev trisomy 35+ is age-related risk X1.7 and any aneuploidy is 1.5
No increased recurrence risk for 2nd+ degree relatives
90% maternal origin, 10% paternal origin
3-4% have translocation, about 1/3 of which are inherited
If father is carrier of a Robertsonian translocation, risk is 0.5-1.5% depending on chromosomes involved
If mother is carrier, risk is about 10-15% in offspring (0-11% for 15;21)
If neither is a carrier, recurrence risk is similar to non-disjunction T21
RARE if t(21;21) translocation, risk is 100% for future offspring.
1% have mosaicism
Similar RR as non-disjunction, though it may overestimate riks
Cannot distinguish T21, translocation or mosaicism based on clinical features.