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Down Syndrome

Down Syndrome (aka trisomy 21) is one of only three thoroughly-studied viable non-mosaic autosomal disorders (the others being trisomies 13 and 18), all of which result in stunted growth, mental retardation and multiple congenital deformities.

The phenotype of Down Syndrome involves: hypotonia (low muscle tone) at birth; dysmorphic facial features; folded, low-set ears; flat nasal bridge; mental retardation, with an average adult IQ or 30-60; and, in about a third of all cases, congenital heart disease. Down Syndrome is the most frequent and studied chromosomal disorder, and can arise in several different ways. All of these avenues somehow involve trisomy of Chromosome 21, and are detailed below.

Trisomy 21Approximately 95% of Down Syndrome cases arise from meiotic nondisjunction of the chromosome 21 pair, leading to trisomy 21. This nondisjunction is maternal in 90% of cases, usually occurring during meiosis I. In the paternal 10% of cases, the nondisjunction usually occurs in meiosis II.
Robertsonian TranslocationApproximately 4% of Down Syndrome patients have Robertsonian translocations. These patients arise when the long arm of Chromosome 21 (Chromosome 21q) fuses with the long arm of another chromosome, and the short arms break off (but are not considered their own chromosome). If this occurs during meiosis, then cells arise that are trisomic for Chromosome 21q, with: 2 normal Chromosome 21's; and a Robertsonian chromosome containing Chromsome 21q and the long arm of another chromosome. Usually a translocation with Chromosome 14, this Robertsonian chromosome is denoted der(14;21).
21q21q TranslocationActually an isochromosome, this situation usually occurs postzygotically when one Chromosome 21 breaks apart into a short arm and a long arm; the long arm duplicates, forming a chromosome composed of two Chromosome 21 long arm.
Mosaic Down SyndromeAccounting for approximately 2% of patients, mosaic Down Syndrome can range from very mild to very severe, depending on the number of affected cells. This variability possibly reflects what proportion of embryonic cells carried the disease genotype.
Partial Trisomy 21There are a few rare patients who have trisomy of only a portion of Chromosome 21; these patients give tremendous insight into which genes are responsible for disease when triplicate.
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