Some specific examples of diseases involving changes in the karyotype are presented next.
Three autosomal trisomies (21, 18, and 13) and one deletion syndrome (cri du chat syndrome), which results from partial deletion of the short arm of chromosome 5, were the first chromosomal abnormalities identified. More recently, several additional trisomies and deletion syndromes (such as those affecting 22q) have been described. Most of these disorders are quite uncommon, but their clinical features should permit ready recognition (
Fig. 7.15
Only trisomy 21 and 22q11.2 deletions occur with sufficient frequency to merit further consideration.
Down syndrome, characterized by extra copy of genes on chromosome 21, is the most common of the chromosomal disorders. About 95% of affected persons have trisomy 21, so their chromosome count is 47. As mentioned earlier, the most common cause of trisomy, and therefore of Down syndrome, is meiotic nondisjunction. The parents of such children are normal in all respects. Maternal age has a strong influence on the incidence of Down syndrome. It occurs in 1 in 1550 live births in women younger than 20 years, in contrast with 1 in 25 live births in women older than 45 years. The correlation with maternal age suggests http://ebooksmedicine.net
Mental retardation Prominent occiput Mental retardation Micrognathia Low set ears Epicanthic folds and flat facial profile Congenital heart defects Intestinal stenosis Gap between first and second toe Umbilical hernia Hypotonia Abundant neck skin Simian crease Predisposition to leukemia TRISOMY 21: DOWN SYNDROME Incidence: 1 in 700 births Karyotypes: Trisomy 21 type: 47,XX, +21 Translocation type: 46,XX,der(14;21)(q10;q10),+21 Mosaic type: 46,XX/47,XX, +21 TRISOMY 13: PATAU SYNDROME Incidence: 1 in 15,000 births Karyotypes: Trisomy 13 type: 47,XX, +13 Translocation type: 46,XX,+13,der(13;14)(q10;q10) Mosaic type: 46,XX/47,XX, +13 TRISOMY 18: EDWARDS SYNDROME Incidence: 1 in 8000 births Karyotypes: Trisomy 18 type: 47,XX, +18 Mosaic type: 46,XX/47,XX, +18 Short neck Overlapping fingers Congenital heart defects Renal malformations Limited hip abduction Microphthalmia Polydactyly Cardiac defects Umbilical hernia Rocker-bottom feet Microcephaly and mental retardation Cleft lip and palate Renal defects Rocker-bottom feet
Fig. 7.15 Clinicalfeaturesandkaryotypesofthethreemostcommonautosomaltrisomies.
http://ebooksmedicine.net that in most cases the meiotic nondisjunction of chromosome 21 occurs in the ovum. Indeed, in 95% of cases the extra chromosome is of maternal origin. The reason for the increased susceptibility of the ovum to nondisjunction with aging is not fully understood. No effect of paternal age has been found in those cases in which the extra chromosome is derived from the father.