Chapter 174

Chromosome disorders and their associated syndromes can be classified into abnormalities of chromosome number and chromosome structure as well as divided into conditions involving autosomes and those involving sex chromosomes.1,2 Three autosomal trisomy syndromes involving chromosomes 21, 18, and 13 and the now well-recognized 22q11 deletion syndrome are the most common disorders involving the autosomes.

Abnormalities of chromosome structure involve duplication or deficiency of a chromosome region or a combination of both. The common deletion syndromes involving terminal (partial) monosomy of chromosomes 4p, 5p, 18p, and 18q were described in the 1960s. However, the introduction of banding techniques led to the recognition and delineation of many other partial monosomy and partial trisomy syndromes since then.1 Whereas many of the phenotypic defects and syndromes caused by chromosome abnormalities have been cataloged, most of these disorders are typified by a consistent pattern of multiple anomalies, growth delays, and developmental disability.1-3 In this section the most common trisomy conditions will be presented; selected deletion syndromes and other aneuploid conditions will also be reviewed.

Chromosome abnormalities occur in about 1 in 150 live births, are responsible for a substantial proportion of genetic diseases, are a major contributor to fetal loss, and are a significant cause of congenital malformations and mental retardation.2 About 15% of all newborns with a congenital malformation and approximately 20% of persons with moderate to severe mental retardation have a chromosomal abnormality.4 Trisomy 21, the most common of the trisomy syndromes, accounts for more than one third of the infants born with a chromosome abnormality, and about 1 in 300 newborns will have an abnormality of one of the sex chromosomes. All the other autosomal disorders of number and structure combined have an overall frequency of less than 1/1000. Of note, balanced rearrangements such as translocations and inversions occur in about 1 in 500 individuals.

Each chromosome syndrome has its own natural history, list of component manifestations, and intrinsic variability. Most disorders of autosomes are associated with alterations of growth and development, such as developmental disabilities, prenatal growth deficiency, short stature, and microcephaly.1 In addition, congenital heart defects are observed with increased frequency in all the well-established chromosome syndromes. Although the separate features of each chromosome syndrome are relatively nonspecific, the total constellation of phenotypic findings in each of the more common syndromes is distinctive enough to permit clinical recognition.3 In particular, this is true of the common autosomal trisomy syndromes and well-established deletion syndromes. Moreover, it is usually the minor anomalies of structure and the alterations of facial morphogenesis that provide the clinical clues that alert the clinician to the possibility of a chromosomal syndrome. Furthermore, a remarkable consistency of the facial gestalt of children with a well-established syndrome at similar ages occurs and is clearly evident by examining photographs of different children with Down syndrome.1,3

The phenotypes of chromosome disorders of structure ...

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