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.
(See also Overview of Chromosomal Abnormalities.)
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 syndrome have hypotonia, feeding problems, failure to thrive, heart defects, developmental delay, and autism.
