22q13

22q13 refers to the distal portion of the long arm of chromosome 22, specifically the region at band q13.3. Deletions or mutations in this region disrupt the SHANK3 gene and most commonly cause Phelan‑McDermid syndrome (PMS), a rare neurodevelopmental disorder. PMS may result from a terminal deletion of 22q13.3 or from pathogenic variants in SHANK3, and sometimes includes additional genes that modify the phenotype.

Clinical features typically include global developmental delay and intellectual disability, absent or severely limited spoken language, and low muscle tone (hypotonia) in infancy. Autistic features are common, and individuals may have feeding difficulties, sleep problems, hypotonia, and minor dysmorphic facial features. Seizures occur in a subset of patients.

Diagnosis is usually made by chromosomal microarray or SNP array to detect 22q13.3 deletions. If a deletion is not found, sequencing of SHANK3 can identify pathogenic variants. Most cases arise de novo, but inherited cases have been reported; parental testing helps determine recurrence risk.

Management is multidisciplinary and supportive. Interventions include physical, occupational, and speech therapy, special education services, and treatment of associated problems such as seizures, reflux, and gastrointestinal issues. There is no cure for PMS; management focuses on maximizing development and quality of life and coordinating medical and educational care. Research continues into SHANK3 function and potential targeted therapies.