microdeletion

Microdeletion is a chromosomal deletion of a small genomic region that is typically too small to be seen on conventional light microscopy. Such deletions usually span tens of kilobases to a few megabases and can remove one or more genes, leading to a distinct clinical syndrome through gene dosage effects or haploinsufficiency.

Detection relies on molecular cytogenetic methods rather than standard karyotyping. Genome-wide approaches such as array comparative genomic hybridization or SNP arrays identify copy number changes, while targeted tests like FISH or MLPA can confirm specific recurrent microdeletions. Parental testing helps determine whether a deletion is de novo or inherited and informs recurrence risk.

Most microdeletions occur through mechanisms such as non-allelic homologous recombination facilitated by flanking segmental duplications, producing recurrent deletions of common size. Nonrecurrent microdeletions can vary in size and gene content. The phenotype depends on the deleted genes and ranges from mild to severe developmental disorders.

Common microdeletion syndromes include 22q11.2 deletion syndrome and Williams syndrome; others involve 5p-, 15q11-q13, 17p11.2, and 4p16.3 deletions. Features commonly include developmental delay or intellectual disability, distinctive facial features, congenital anomalies, and variable cardiovascular, renal, or endocrine problems.

Management is multidisciplinary and tailored to the individual, emphasizing developmental therapies, medical surveillance for associated anomalies, and genetic counseling. Prognosis varies widely by syndrome and by individual; many affected individuals achieve meaningful milestones with appropriate support.