Contiguous gene syndromes are disorders caused by microscopic and submicroscopic deletions or duplications of contiguous genes on particular parts of chromosomes. These syndromes differ from chromosomal deletion syndromes (Chromosomal Anomalies: Chromosomal Deletion Syndromes) in that deletion syndromes are usually visible on karyotyping because of their larger size (typically > 5 megabases), whereas the abnormalities in contiguous gene syndromes involve smaller segments (typically 1 to 3 megabases) and are detectable only with fluorescent probes (fluorescent in situ hybridization) and microarray analysis. A given gene segment can be deleted or duplicated (termed a reciprocal duplication). The clinical effects of microscopic reciprocal duplications tend to be similar but less severe than those of deletions involving the same segment.

Most clinically significant microdeletions and duplications seem to occur sporadically; however, mildly affected parents may be diagnosed when parental testing is done after a child is found to have an abnormality. Numerous syndromes have been identified, with widely varying manifestations (see Table 2: Chromosomal Anomalies: Examples of Contiguous Gene Deletion Syndromes).

Table 2
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Examples of Contiguous Gene Deletion Syndromes Syndrome Chromosomal Deletion Description Alagille syndrome 20p.12 Cholestasis, bile duct paucity, cardiac anomalies, pulmonary artery stenosis, butterfly vertebrae, posterior embryotoxon of the eye Angelman syndrome Maternal chromosome at 15q11 Seizures, puppet-like ataxia, frequent laughter, hand flapping, severe intellectual disability DiGeorge syndrome (DiGeorge anomaly, velocardiofacial syndrome, pharyngeal pouch syndrome, thymic aplasia—see Immunodeficiency Disorders: DiGeorge Syndrome) 22q11.21 Hypoplasia or lack of thymus and parathyroids, cardiac anomalies, cleft palate, intellectual disability, psychiatric problems Langer-Giedion syndrome (trichorhinophalangeal syndrome type II) 8q24.1 Exostosis, cone epiphyses, sparse hair, bulbous nose, hearing loss, intellectual disability Miller-Dieker syndrome 17p13.3 Lissencephaly; short, upturned nose; severe growth retardation; seizures; severe intellectual disability Prader-Willi syndrome (see Endocrine Disorders in Children: Secondary) Paternal chromosome at 15q11 In infancy: Hypotonia, poor feeding, failure to thrive In childhood and adolescence: Obesity, hypogonadism, small hands and feet, intellectual disability, obsessive-compulsive behaviors Rubinstein-Taybi syndrome 16p13− Broad thumbs and large toes, prominent nose and columella, intellectual disability Smith-Magenis syndrome 17p11.2 Brachycephaly, midfacial hypoplasia, prognathism, hoarse voice, short stature, intellectual disability Williams syndrome 7q11.23 Aortic stenosis, intellectual disability, elfin facies, transient hypercalcemia in infants

Last full review/revision December 2012 by Nina N. Powell-Hamilton, MD

Content last modified January 2013