22q13 deletion syndrome (Phelan McDermid syndrome)

Page most recently updated 7 September 2026

This page focuses on the reported psychiatric associations, which may be the initial presenting manifestation, and on other clinical features that may assist the psychiatrist or primary care physician in identifying the underlying diagnosis, considered through the lenses of the diagnostic lenses framework.

22q13 deletion syndrome (Phelan-McDermid syndrome) is a rare genetic disorder caused by deletion of part of the terminal region of the long arm of chromosome 22. It can occur as an inherited or de novo genetic condition, so absence of a relevant family history does not exclude the diagnosis. Most cases arise de novo, although inherited cases can occur. In some individuals, the deletion occurs as part of a ring chromosome 22 (a circular form of chromosome 22 formed when the chromosome ends join together). A distinctive presentation may include the combination of long eyelashes, bulbous nose, and large fleshy hands.

It can present with psychiatric features such as autism spectrum disorder (ASD), ADHD, anxiety, mood disorders, behavioral dysregulation, aggression, and self-injurious behavior. Repetitive and stereotypic behaviors and sleep disturbance are also common. Mood cycling, psychotic symptoms, and catatonia may emerge particularly during adolescence or adulthood and may be associated with regression or loss of previously acquired skills. Cognitive impairment, developmental delay, and severe speech and language impairment are common, with some individuals having absent or very limited expressive speech. These manifestations generally emerge during childhood or development, although neuropsychiatric difficulties may become more prominent later in development and may be associated with functional regression.

From a morphologic lens perspective, other features include (but are not limited to):

  • Prominent forehead

  • Fullness of eyelids

  • Bulbous nose

  • Syndactyly (2nd and 3rd toes)

Other characteristic features include hypotonia, seizures/epilepsy, ataxia or abnormal gait, and sleep disturbance. Neurologic manifestations may include structural brain abnormalities and developmental or functional regression. Other recognized features include decreased pain perception, lymphedema, feeding difficulties, gastroesophageal reflux, decreased perspiration with a tendency to overheat, hearing and visual abnormalities, congenital heart defects, and renal and urogenital abnormalities. In individuals with a ring chromosome 22, there is an increased risk of NF2-related tumours, including vestibular schwannomas, meningiomas, and spinal and peripheral schwannomas.

Early diagnosis is important to identify and monitor potentially serious neurologic, cardiac, renal, and gastrointestinal complications, recognize neuropsychiatric needs early, and institute tailored multidisciplinary surveillance and treatment.

Selected references and further reading — Morphologic lens

Jones KL, Jones MC, del Campo M. Smith's recognizable patterns of human malformation. 8th ed. Philadelphia: Elsevier; 2021.

Reardon W. The bedside dysmorphologist: a guide to identifying and assessing congenital malformations. 2nd ed. Oxford: Oxford University Press; 2016.

Allanson JE, Biesecker LG, Carey JC, Hennekam RCM. Elements of morphology: introduction. Am J Med Genet A. 2009;149A(1):2-5. doi:10.1002/ajmg.a.32601.

Hennekam RCM, Biesecker LG, Allanson JE, Hall JG, Opitz JM, Temple IK, Carey JC; Elements of Morphology Consortium. Elements of morphology: general terms for congenital anomalies. Am J Med Genet A. 2013;161A(11):2726-2733. doi:10.1002/ajmg.a.36249.