Phelan-McDermid syndrome, 22q13 deletion syndrome, is a genetic condition caused by the deletion of the terminal end of chromosome 22 or mutation of the SHANK3 gene.
The genetic changes that cause PMS vary from person to person and can occur from a de novo mutation or be inherited (autosomal dominant). Global developmental delay, intellectual disability of varying degrees, autism or autistic-like behaviour, hypotonia, epilepsy, absent or severely delayed speech, gastroesophageal reflux, syndactyly, genitourinary abnormalities, brain structural abnormalities such as microcephaly and distinctive facial features with possible tracheal stenosis may occur. Chromosomal microarray is the most common method for diagnosing Phelan-McDermid syndrome. Fluorescence in situ hybridisation (FISH) may detect larger deletions. If a diagnosis of Phelan-McDermid syndrome is suspected, but no deletion of 22q13 is detected by microarray, targeted DNA sequencing may detect mutations of the SHANK3 gene. Mitochondrial abnormalities, specifically abnormalities in complex I and IV activity, may explain some phenotypic variation in PMS individuals.