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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.
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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.
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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.
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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
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The phenotypes of chromosome disorders of structure ...