Genetics, Dysmorphology, and Congenital Anomalies
Common aneuploidies and syndromes
Trisomy 21: hypotonia, upslanting palpebral fissures, single palmar crease, sandal gap, atrioventricular canal, duodenal atresia, and Hirschsprung disease. Trisomy 18 and 13: growth restriction, clenched hands, rocker-bottom feet, congenital heart disease, and poor survival. Turner syndrome (45,X): cystic hygroma, coarctation, lymphedema, and gonadal dysgenesis. Klinefelter (47,XXY): minimal newborn findings.
Dysmorphology
Take a three-generation pedigree and describe minor anomalies precisely: preauricular pits, single transverse crease, clinodactyly. Three or more minor anomalies increase the chance of a syndrome. 22q11.2 deletion causes conotruncal heart defects, hypocalcemia, thymic hypoplasia, and palatal anomalies. Prenatal cell-free DNA is a screening test, not diagnostic; chromosomal microarray is first-tier for congenital anomalies.
Worked example
A newborn has a cleft palate, hypocalcemia, and interrupted aortic arch. Reasoning: this constellation suggests 22q11.2 deletion. Order FISH or microarray, check calcium and lymphocytes, involve feeding and immunology teams, and counsel the family.
Traps
- Calling a normal variant dysmorphic.
- Treating cell-free DNA as diagnostic.
- Missing that an apparently isolated cleft palate can be part of a syndrome.