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 and microduplication syndromes are genomic disorders caused by submicroscopic chromosomal deletions or duplications (copy number variants) that typically result in a heterogeneous spectrum of neurodevelopmental, cognitive, behavioral, and congenital anomalies, with variable expressivity and variable expressivity depending on the specific genomic region involved.
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 are now more clearly defined.
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 usually involve smaller segments (typically 1 to 3 megabases) and are detectable only with fluorescent probes (fluorescent in situ hybridization) and chromosomal microarray analysis (1). 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 in which genes are clustered together; it is commonly associated with microdeletions but may also be associated with microduplications.
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, which is estimated to occur in 1/25,000 people worldwide (2). Infants with this syndrome have hypotonia, feeding problems, growth and weight faltering (formerly failure to thrive), heart defects, developmental delay, and autism spectrum disorder.
Williams-Beuren syndrome is another multisystem genetic condition caused by a microdeletion on chromosome 7 (at band q11.23) (3). It is characterized by the presence of distinctive facial features, intellectual disability with retained verbal skills, and a sociable, outgoing personality with a tendency for anxiety and phobias. Cardiovascular complications include supravalvular aortic stenosis.
(See also Next-generation sequencing technologies.)
Examples of Microdeletion Syndromes
Syndrome | Chromosomal Deletion | Description |
|---|---|---|
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 delay; seizures; severe intellectual disability |
Paternal chromosome at 15q11 | In infancy: Hypotonia, poor feeding, growth and weight faltering (formerly 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 |
References
1. Wetzel AS, Darbro BW. A comprehensive list of human microdeletion and microduplication syndromes. BMC Genom Data. 2022;23(1):82. Published 2022 Nov 26. doi:10.1186/s12863-022-01093-3
2. MedlinePlus [Internet]. Bethesda (MD): National Library of Medicine (US); [updated 2020 Jun 24]. Potocki-Lupski syndrome; [updated 2020 Jun 10; reviewed 2017 Oct 1; cited 2025 Jul 29]; [about 5 p.]. Available from: https://medlineplus.gov/genetics/condition/potocki-lupski-syndrome/.
3. Osborne LR, Mervis CB. 7q11.23 deletion and duplication. Curr Opin Genet Dev. 2021;68:41-48. doi:10.1016/j.gde.2021.01.013
