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Microduplication syndromes

Carlos A Bacino, MD, FACMG
Section Editor
Helen V Firth, DM, FRCP, DCH
Deputy Editor
Elizabeth TePas, MD, MS


Microduplications, or submicroscopic duplications, are chromosomal duplications that are too small to be detected by light microscopy using conventional cytogenetics methods. Specialized testing is needed to identify these duplications. Microduplications are typically one to three megabases (Mb) long and involve several contiguous genes. The exact size and location of a microduplication that causes a syndrome may vary, but a specific "critical region" may be consistently involved. Most of the phenotypic effects of these microduplications are due to changes in a few critical dose-sensitive genes or, in some cases, a single gene if a duplication disrupts its integrity.

The phenotype of microduplication syndromes is often less clear and less well defined than for the corresponding microdeletion syndrome. In addition, some microduplication syndromes may be inherited from apparently normal parents, raising important issues regarding incomplete penetrance and ascertainment bias in these newly described clinical entities.

This topic reviews microduplication syndromes of chromosomes 1 to 22. Microdeletion syndromes, congenital abnormalities of the sex chromosomes, and other congenital chromosomal abnormalities, such as trisomies, are reviewed in detail elsewhere. (See "Microdeletion syndromes (chromosomes 1 to 11)" and "Microdeletion syndromes (chromosomes 12 to 22)" and "Sex chromosome abnormalities" and "Congenital cytogenetic abnormalities".)


Genomic disorders are diseases that result from the loss or gain of chromosomal/DNA material. The most common and better delineated genomic disorders are divided in two main categories: those resulting from copy number losses (deletion syndromes) and those resulting from copy number gains (duplication syndromes). (See "Genomic disorders: An overview".)

Copy number variations (CNVs) are submicroscopic genomic differences in the number of copies of one or more sections of DNA that result in DNA gains or losses (figure 1). Some CNVs are pathogenic and cause syndromic disorders with consistent phenotypic features, as are discussed here. Other CNVs are associated with disease susceptibility or resistance, and the same CNV can be associated with several diverse disorders. Still, other CNVs are part of normal genetic variation and have no recognized disease association. Contiguous gene syndromes can occur when CNVs affect several adjacent genes. (See "Overview of genetic variation", section on 'Copy number variations (CNVs)' and "Basic principles of genetic disease", section on 'Copy number variation'.)

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Literature review current through: Sep 2017. | This topic last updated: Jun 24, 2016.
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