The most common trisomy among live births is chromosome 21 or Down's syndrome, deriving its eponym from Langdon Down, who first described the clinical features in 1866.79 Systemic findings include hypotonia; brachycephaly; a large protruding tongue; small nose with a low, small bridge; small, poorly defined ears; short, thick neck; stubby hands with a single palmar crease; clinodactyly of fifth digit with hypoplasia of mid-digital phalanges; short, stubby feet with a wide gap between first and second toes; and cardiac malformations. Affected individuals have a higher incidence of leukemia. Males are usually sterile; females, on occasion, are fertile.280
The ocular features include epicanthus, upward slanting of the palpebral fissures, myopia, strabismus, nystagmus, blepari-tis, ectropion of the eyelids, keratoconus, Brushfield spots of the irides, infantile glaucoma, congenital or acquired cataracts, and an increased number of retinal vessels crossing the disc margin.42'46 130'322,353 The pathological features include focal condensation or hyperplasia of the iris in the region of the Brushfield spots, choroidal congestion, elongation of the ciliary processes, and focal hyperplasia of the retinal pigment epithelium.130,131
Most affected children have 47 chromosomes with an extra chromosome 21.194 About 5% have 46 chromosomes with a translocation involving chromosome 13, 14, or 15, with 14 being most frequent, or a Robertsonian translocation involving either chromosome 21 or 22 (G group), with 21 being most frequent. The translocation may be inherited from a phenotypically normal parent with 45 chromosomes. There are no clinical differences between children with Down's syndrome caused by trisomy 21 or by a translocation. The overall incidence of Down's syndrome is 1 in 700 live births and is age dependent. The risk increases with increasing maternal age. The recurrence risk for parents of a child with Down's syndrome is about 1% if both parents have normal chromosomes. In the event of a parental translocation, the risk is higher if the mother is the carrier; in the rare case of a 21;21 translocation in a parent, all the offspring will have Down's syndrome (see Fig. 3-7).
Mosaicism for trisomy 21 is common. The clinical manifestations vary from a normal phenotype to that of typical Down syndrome.
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