CLIPP case 29. Infant with hypotonia (Trisomy 21, Congenital) Flashcards
4 day-old boy born via midwife presents for weight check. On exam, he is hypotonic with flattened mid-face, epicanthal folds, incurving of fifth fingers, and mild diastasis recti.
Down syndrome
- Diagnosis: Lymphocyte karyotyping shows trisomy 21
- Screening: hearing, vision, echocardiogram, thyroid studies, and atlantoaxial instability (C1-C2)
DDx of hypotonia
-Benign neonatal hypotonia: dx of exclusion
-Down syndrome
-Zellweger syndrome: peroxisomal disorder
Less likely:
-Perinatal asphyxia
-Metabolic abnormality
-Effect of maternal medications
-Other chromosomal abnormality
-Sepsis
-Central nervous system abnormality
Down Syndrome epidemiology
- Probably the most common cause of mental retardation that involves genetic material
- Prevalence: 1 in 700
Down Syndrome karyotypes
- Trisomy 21 (most common, regardless of mother’s age)
- Unbalanced translocations
- Mosaicism for a trisomy 21 cell line
Down Syndrome clinical features
- Mental retardation
- Heart defects (50%)
- Intestinal stenosis, umbilical hernia
- Leukemia predisposition
- Hypothyroidism (test often)
- Hypotonia (most consistent finding), short stature
- Epicanthic folds, flat facies, redundant nuchal folds
- Single palmar crease, gap b/t first and second toes
Down Syndrome risk factors
- Maternal age > 35 at delivery, although majority of Down syndrome pregnancies occur to women under age 35
- No strong paternal age effect
- Consanguinity is NOT a risk factor
Patau Syndrome
- Trisomy 13
- Incidence 1/10,000 births
- Clinical features: microphthalmia, microcephaly, severe mental retardation, polydactyly, cleft lip and palate, cardiac and renal defects, umbilical hernia, cutis aplasia
Edwards Syndrome
*Trisomy 18
-Incidence 1/6,000 births
-Clinical features: severe mental retardation, prominent occiput, micrognathia, low-set ears, short neck, overlapping fingers, heart defects,
renal malformations, limited hip abduction, rocker-bottom feet
Fragile X Syndrome
- Most common familial cause of MR
- Caused trinucleotide (CGG) repeats outside the coding region of the FMR1 gene on the X chromosome
- Clinical features: large testicles (after puberty); large, everted ears; long face with large mandible
Turner Syndrome
*45X
-Incidence 1/2000 female live births (but 99% of conceptuses with Turner syndrome miscarry)
-More likely to be associated with physical differences at birth
-Clinical features: Normal IQ, lymphedema in utero (webbed neck, low placement of ears, edema of the hands and feet), hyperconvex nails, “shield” chest, widely spaced nipples, Coarctation of the aorta (20%)
Short stature
Gonadal dysgenesis
Klinefelter Syndrome
- 47XXY
- Usually normal at birth
- Clinical features: IQ low-normal range, often infertility due to testicular atrophy, eunuchoid body habitus, gynecomastia in adolescence
How many generations should you cover in creating a family pedigree?
3
Indication for chromosome studies in an infant
- Clinical features of a known chromosome disorder (such as Down syndrome)
- Unrecognized malformation syndrome
- Known genetic condition but with additional or more severe findings
- Mental retardation and other unusual findings (including short stature)
- Stillborn with multiple malformations
- Features of a chromosome breakage syndrome
- Tumor (including leukemia) that may be associated with chromosome abnormalities (can study a specific tissue)
Prenatal screening (Down’s)
Chromosome analysis of:
- Chorionic villus sampling (CVS)
- Amniotic fluid cells
Down Syndrome Management
-Hearing and vision screenings
-Pediatric cardiology referral and echo
-Repeat thyroid studies 6 mo and annually:
incidence of both congenital hypothyroidism and hypothyroidism is increased
-X-rays for atlantoaxial instability, especially at school age
-Consider the predisposition for leukemia
