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Microdeletion and Microduplication Syndromes

By

Nina N. Powell-Hamilton

, MD, Sidney Kimmel Medical College at Thomas Jefferson University

Last full review/revision Jun 2020| Content last modified Jun 2020
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Microdeletion and microduplication syndromes are disorders caused by submicroscopic deletions or duplications of contiguous genes on particular parts of chromosomes. Postnatal diagnosis is suspected by clinical appearance and preferably confirmed by chromosomal microarray analysis or by fluorescent in situ hybridization.

Microdeletion syndromes are better defined than are microduplication syndromes, and the significance of many microduplications is still unclear. The reciprocal duplications of well-recognized microdeletions such as 22q11.2 and 7q11.23 have been more clearly defined in recent years.

Microdeletion syndromes differ from chromosomal deletion syndromes in that chromosomal deletion syndromes are usually visible on karyotyping because of their larger size (typically > 5 megabases), whereas the abnormalities in microdeletion syndromes involve smaller segments (typically 1 to 3 megabases) and are detectable only with fluorescent probes (fluorescent in situ hybridization) and chromosomal microarray analysis. A given gene segment can be deleted and 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. The term contiguous gene syndrome typically refers to a condition that is commonly associated with microdeletions but that can also be associated with microduplications in which genes are clustered together. (See also Next-generation sequencing technologies.)

Most clinically significant microdeletions and microduplications 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 microdeletion syndromes have been identified, with widely varying manifestations (see Table: Examples of Microdeletion Syndromes).

Reciprocal microduplication involving chromosome 17p11.2 is associated with Potocki-Lupski syndrome. Infants with this disorder have hypotonia, feeding problems, failure to thrive, heart defects, developmental delay, and autism.

Table
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Examples of Microdeletion 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)

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

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

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