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Microdeletion syndromes (chromosomes 12 to 22)

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


Chromosome deletions that span at least 5 megabases (Mb) are usually microscopically visible on chromosome-banded karyotypes. Microdeletions, or submicroscopic deletions, are chromosomal deletions that are too small to be detected by light microscopy using conventional cytogenetic methods. Specialized testing is needed to identify these deletions. Microdeletions are typically 1 to 3 Mb long and involve several contiguous genes. The exact size and location of a microdeletion that causes a syndrome may vary, but a specific "critical region" is consistently involved. Most phenotypic effects of these microdeletions are due to haploinsufficiency of a few critical genes or, in some cases, a single gene.

This topic reviews microdeletion syndromes involving chromosomes 12 through 22. Microdeletion syndromes involving chromosomes 1 through 11 are discussed separately, as are microduplication syndromes and congenital abnormalities of the sex chromosomes. Other congenital chromosomal abnormalities, such as trisomies, are also reviewed in detail elsewhere. (See "Microdeletion syndromes (chromosomes 1 to 11)" and "Microduplication syndromes" 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 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'.)

The main mechanism that leads to disease in genomic disorders secondary to deletions and duplications is a change in the copy number of a dose-sensitive gene or genes. Other disease mechanisms include interference with imprinted genes and with regulatory elements outside genes. (See "Genomic disorders: An overview", section on 'Disease mechanisms'.)

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Literature review current through: Sep 2017. | This topic last updated: Jun 20, 2016.
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