Pitt-Hopkins 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.

Pitt-Hopkins syndrome is a rare genetic condition. It usually occurs as a de novo genetic condition, although it can occasionally be inherited from an affected parent as an autosomal dominant condition; therefore, absence of a relevant family history does not exclude the diagnosis. A distinctive presentation may include the combination of severe intellectual disability and absent or severely limited speech, characteristic facial features including a wide mouth, episodic hyperventilation/apnoea, and a typically cheerful or excitable demeanour.

It can present with psychiatric features such as autism spectrum disorder (ASD), ADHD, anxiety, behavioural dysregulation, stereotypic behaviours, irritability and self-injurious behaviour. Features of ASD are common, although social interest and a generally happy or excitable affect may be relatively preserved. Anxiety and behavioural difficulties have been reported in adolescents and adults. The neurodevelopmental manifestations generally emerge during infancy or early childhood, and late-onset psychiatric presentations in adulthood are not characteristic.

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

  • Prognathism

  • Upslanted palpebral fissures

  • Broad nasal bridge

  • Thick vermilion

  • Wide mouth

  • Widely spaced teeth

  • Clinodactyly of fifth fingers

  • Prominent fingertip pads

  • Single transverse palmar crease

Other characteristic features include severe developmental delay and intellectual disability, with marked impairment of expressive language and absent or severely limited speech. Neurological manifestations may include hypotonia, motor delay, ataxia, gait abnormalities and seizures. A characteristic respiratory abnormality consists of episodes of rapid breathing followed by breath-holding or apnoea, often occurring during wakefulness and sometimes triggered by excitement or anxiety. These episodes are variable and may emerge during later childhood or adolescence; their absence does not exclude the diagnosis. Constipation and gastroesophageal reflux are common, and visual abnormalities, particularly severe myopia and strabismus, are frequent. Other reported features include sleep disturbance, scoliosis, flat feet, urinary retention and, less commonly, congenital heart and genitourinary abnormalities. The facial phenotype may become more distinctive with age.

Early diagnosis is important to identify and manage respiratory abnormalities and seizures; distinguish characteristic episodes of hyperventilation and apnoea from behavioural or psychiatric phenomena; assess associated gastrointestinal, visual, musculoskeletal and other medical complications; provide appropriate developmental, educational and psychiatric assessment and support; and facilitate genetic counselling and recurrence-risk assessment for the family.

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.