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Chromosomal
deletion syndromes result from loss of parts of chromosomes. They
tend to cause severe congenital anomalies and markedly retarded
mental and physical development. Chromosomal deletion syndromes
are rarely suspected prenatally but may be incidentally discovered
at that time if karyotyping is done for other reasons. Postnatal
diagnosis is suspected by clinical appearance and is confirmed by
karyotyping and other genetic analysis.
5p-Deletion
(cri du chat syndrome):
Deletion of the end of the short arm of chromosome 5 (5p) (usually paternal) is characterized by a high-pitched, mewing cry, closely resembling the cry of a kitten, which is heard in the immediate neonatal period, lasts several weeks, and then disappears. Affected neonates are hypotonic and have low birth weight, microcephaly, a round face with wide-set eyes, downward slanting of the palpebral fissures (with or without epicanthal folds), strabismus, and a broad-based nose. The ears are low-set, abnormally shaped, and frequently have narrow external auditory canals and preauricular tags. Syndactyly, hypertelorism, and heart anomalies occur often. Mental and physical development is markedly retarded. Many affected children survive into adulthood but have significant disability.
4p-Deletion
(Wolf-Hirschhorn syndrome):
Deletion of the short arm of chromosome 4 (4p) results in profound mental retardation. Manifestations also may include epilepsy, a broad or beaked nose, midline scalp defects, ptosis and colobomas, cleft palate, delayed bone development, and, in boys, hypospadias and cryptorchidism. Many affected children die during infancy; those who survive into their 20s have severe disability.
Contiguous
gene syndromes:
These include microscopic and submicroscopic deletions of contiguous genes on particular parts of many chromosomes; small duplications of chromosomes also occur. The effects of duplications, however, are usually milder than those of deletions. Almost all cases are sporadic; however, mildly affected parents, as in some 22q11.21 deletions, can pass on the syndrome. Numerous syndromes have been identified, with widely varying manifestations (see Table 2: Chromosomal Anomalies: Examples of Contiguous Gene Syndromes ). Deletions and duplications are often detectable with fluorescent probes and other techniques. Sometimes deletions and duplications cannot be shown cytogenetically, but their presence can be confirmed by DNA probes specific to the deleted or duplicated area.
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Table 2
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Examples of Contiguous
Gene Syndromes
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Syndrome
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Chromosomal Deletion
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Description
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Alagille syndrome
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20p.12
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Cholestasis, bile duct paucity, cardiac anomalies, pulmonary artery stenosis, butterfly vertebrae, posterior embryotoxon of the eye
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Angelman's syndrome
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Maternal chromosome at 15q11
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Seizures, puppet-like ataxia, frequent laughter, hand flapping, severe mental retardation
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DiGeorge syndrome (DiGeorge anomaly, velocardiofacial syndrome, pharyngeal pouch syndrome, thymic aplasia—see Immunodeficiency Disorders: DiGeorge Syndrome)
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22q11.21
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Hypoplasia or lack of thymus and parathyroids, heart anomalies, cleft palate, mental retardation, and psychiatric problems
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Langer-Giedion syndrome (trichorhinophalangeal syndrome type II)
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8q24.1
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Exostosis, cone epiphyses, sparse hair, bulbous nose, hearing loss, mental retardation
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Miller-Dieker syndrome
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17p13.3
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Lissencephaly; short, upturned nose; severe growth retardation; seizures; severe mental retardation
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Prader-Willi syndrome (see Endocrine Disorders in Children: Secondary)
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Paternal chromosome at 15q11
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In infancy: Hypotonia, poor feeding, failure to thrive
In childhood and adolescence: Obesity, hypogonadism, small hands and feet, mental retardation, obsessive-compulsive behaviors
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Rubinstein-Taybi syndrome
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16p13−
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Broad thumbs and large toes, prominent nose and columella, mental retardation
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Smith-Magenis syndrome
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17p11.2
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Brachycephaly, midfacial hypoplasia, prognathism, hoarse voice, short stature, mental retardation
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Williams syndrome
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7q11.23
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Aortic stenosis, mental retardation, elfin facies, transient hypercalcemia in infants
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Telomeric
deletions:
These deletions are small and often submicroscopic and may occur at either telomere (the end of a chromosome). Phenotypic changes may be minimal. Telomeric deletions may account for many cases of nonspecific mental retardation in which the affected person has mildly dysmorphic features.
Last full review/revision December 2008 by Gregory S. Liptak, MD, MPH
Content last modified December 2008
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