microdeletions

Microdeletions are submicroscopic chromosomal abnormalities in which a small segment of DNA, typically ranging from a few kilobases to several megabases, is missing from the genome. They are not detectable by conventional karyotyping but can be identified using molecular techniques such as fluorescence in situ hybridization (FISH), microarray comparative genomic hybridization (aCGH), or next‑generation sequencing. The loss of genetic material can disrupt one or more genes, leading to a spectrum of phenotypic effects that vary according to the size of the deletion, the genes involved, and the presence of additional genetic or environmental modifiers.

Clinically, microdeletions are linked to a number of developmental and neuropsychiatric disorders. Well‑characterized syndromes include 22q11.2 deletion syndrome (DiGeorge/velocardiofacial syndrome), 15q13.3 microdeletion associated with epilepsy and intellectual disability, and 16p11.2 deletion linked to autism spectrum disorder and obesity. In many cases, the same microdeletion may be found in individuals with mild or no observable symptoms, highlighting variable penetrance and expressivity.

The detection of microdeletions has important implications for diagnosis, genetic counseling, and management. Early identification can guide surveillance for associated medical complications, inform prognosis, and facilitate tailored interventions. For families, understanding the recurrence risk is essential; many microdeletions arise de novo, while others are inherited in an autosomal dominant or X‑linked pattern.

Research continues to elucidate the functional consequences of specific microdeletions, their role in complex traits, and potential therapeutic strategies. Advances in high‑resolution genomic technologies are expanding the catalog of pathogenic microdeletions, improving the ability to diagnose rare genetic conditions and refine genotype‑phenotype correlations.