DS is the most common abnormality of chromosomal number. It occurs in 1 of every 1000 births. Most cases (92.5%)are due to nondisjunction; in 68%, the nondysjunctionalevent occurs in maternal meiosis phase I. As a result ofnondisjunction, there are three copies of chromosome 21(trisomy 21); using standard cytogenetic nomenclature, trisomy 21 is designated 47,XX,+21 or 47,XY,+21. In 4.5%of cases, the extra chromosome is part of a robertsonian translocation, which occurs when the long arms (q) of twoacrocentric chromosomes (numbers 13, 14, 15, 21, or 22)fuse at the centromeres, and the short arms (p), containing copies of ribosomal RNA, are lost. The most commonrobertsonian translocation leading to DS involves chromosomes 14 and 21; standard nomenclature is 46,XX,t(14q21q)or 46,XY,t(14q21q). The parents of DS infants with trans-locations should have a karyotype to exclude a balancedtranslocation.
In approximately 1% to 2% of children with DS, mosaicism occurs. These individuals have two populations of cells: one with trisomy 21 and one with a normal chromosome complement. Mosaicism results from a either a nondisjunctional event that occurs after fertilization and after a few cell divisions, or from trisomic rescue. The loss of this aneuploidy returns the cell to 46,XX or 46,XY. In either case, the individual is referred to as a mosaic for these two populations of cells and is designated 47,XX, +21/46XX or 47,XY,+21/46,XY. Although it is widely believed that individuals with mosaic DS are more mildly affected, there are wide variations in the clinical findings.
Children with DS are most likely diagnosed in the newbornperiod. These infants tend to have normal birth weight andlength, but are hypotonic. The characteristic facial appearance,with brachycephaly, flattened occiput, hypoplastic midface, flattened nasal bridge, upslanting palpebral fissures, epicanthal folds,and large protruding tongue, is apparent at birth. Infants also haveshort broad hands, often with a single transverse palmar crease,and a wide gap between the first and second toes. The severe hypotonia may cause feeding problems and decreased activity.
Approximately 50% of children with DS have congenital heart disease, including atrioventricular canal, ventriculoseptal or atrioseptal defects, and valvular disease. Approximately 10% of newborns with DS have gastrointestinal tract anomalies. The three most common defects are duodenal atresia, annular pancreas, and imperforate anus.
Four percent to 18% of infants with DS are found to have congenital hypothyroidism, which is identified as part of the newborn screening program. Acquired hypothyroidism is a more common problem. Thyroid function testing must be monitored periodically during the child’s life.