22q11.2 microdeletion syndrome (velocardiofacial syndrome, DiGeorge syndrome, Shprintzen 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.

22q11.2 microdeletion syndrome is a genetic disorder that can affect neurodevelopment, mental health, and multiple organ systems. The designation “22q11.2” is pronounced “twenty-two Q one-one point two.” It can occur as an inherited or de novo genetic condition, so absence of a relevant family history does not exclude the diagnosis.

It can present with psychiatric features such as anxiety, depression, attention-deficit symptoms, social difficulties, behavioural problems, cognitive and learning difficulties, and schizophrenia-spectrum disorders, including psychosis. Psychiatric manifestations may emerge during adolescence or adulthood, even when the characteristic congenital features were not previously recognized.

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

  • Microcephaly

  • Micrognathia

  • Widely spaced eyes

  • Short palpebral fissure

  • Telecanthus

  • Downslanted palpebral fissures

  • Underdeveloped alae nasi

  • Bulbous nose

  • Short philtrum

  • Cleft palate (including submucous cleft palate)

Other characteristic features include developmental delay, intellectual disability, speech and learning problems, and seizures in some individuals. Immune deficiency related to thymic hypoplasia or dysfunction and hypoparathyroidism with hypocalcaemia are also characteristic features. The clinical phenotype is highly variable, and adults may present predominantly with psychiatric or other later-onset manifestations despite the absence of a previously recognized congenital syndrome.

From a multisystemic lens perspective, clinical features in other body systems include (but are not limited to):

  • Cardiovascular: congenital heart disease, particularly conotruncal abnormalities such as ventricular septal defect, tetralogy of Fallot, interrupted aortic arch, and truncus arteriosus; aortic root dilatation and other cardiovascular abnormalities may also occur.

  • Respiratory: recurrent respiratory infections related to immune dysfunction, as well as laryngotracheal abnormalities and structural airway problems.

  • Renal/electrolytes: renal and urinary tract anomalies may occur; hypocalcaemia related to hypoparathyroidism is characteristic and may recur during periods of physiological stress.

  • Gastrointestinal: feeding difficulties, gastroesophageal reflux, gastrointestinal dysmotility, constipation, and other gastrointestinal abnormalities may occur.

  • Endocrine: hypoparathyroidism and hypocalcaemia, hypothyroidism, and, less commonly, growth hormone deficiency may occur.

  • Hematologic: cytopenias, including thrombocytopenia, neutropenia, and autoimmune haemolytic anaemia, may occur, reflecting the broader immune dysregulation associated with the syndrome.

  • Musculoskeletal: scoliosis, vertebral and rib abnormalities, cervical spine abnormalities, and other skeletal anomalies may occur.

Early diagnosis is important to identify potentially treatable medical contributors to psychiatric and cognitive presentations, recognize congenital cardiac, immune, endocrine, renal, and other systemic complications, guide appropriate surveillance and genetic counselling, and enable timely treatment of psychiatric illness and other comorbidities.

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.

Selected references and further reading — Multisystemic lens

Cardinal RN, Bullmore ET. The diagnosis of psychosis. Cambridge: Cambridge University Press; 2011.

Sachdev PS, Keshavan MS, editors. Secondary schizophrenia. Cambridge: Cambridge University Press; 2010.

Levenson JL, editor. The American Psychiatric Association Publishing textbook of psychosomatic medicine and consultation-liaison psychiatry. 3rd ed. Washington (DC): American Psychiatric Association Publishing; 2019.

Stern TA, Beach SR, Smith FA, Freudenreich O, Vranceau AM, Fava M, editors. Massachusetts General Hospital handbook of general hospital psychiatry. 8th ed. Philadelphia: Elsevier; 2025.

Arciniegas DB, Yudofsky SC, Hales RE, editors. The American Psychiatric Association Publishing textbook of neuropsychiatry and clinical neurosciences. 6th ed. Washington (DC): American Psychiatric Association Publishing; 2018.

Agrawal N, Faruqui R, Bodani M, editors. Oxford textbook of neuropsychiatry. Oxford: Oxford University Press; 2020.

Boland R, Verduin M, editors. Kaplan and Sadock's comprehensive textbook of psychiatry. 11th ed. Philadelphia: Wolters Kluwer; 2024.

Loscalzo J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, editors. Harrison's principles of internal medicine. 22nd ed. New York: McGraw Hill; 2025.