9q34.3 subtelomeric deletion syndrome (Kleefstra 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.

9q34.3 subtelomeric deletion syndrome (Kleefstra syndrome) is a rare genetic disorder caused by deletion of part of the terminal region of the long arm of chromosome 9. 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 rare inherited cases can occur. A distinctive presentation may include the combination of synophrys, everted lower lip vermilion, and relative prognathism.

It can present with psychiatric features such as autism spectrum disorder (ASD), stereotypic behaviors, anxiety, mood disorders, and psychotic disorders. Sleep disturbance and behavioral dysregulation are also common. A particularly distinctive neuropsychiatric presentation is extreme apathy and catatonic-like behavior emerging after puberty, which may be associated with psychosis and functional regression. Cognitive impairment, developmental delay, and severe speech and language impairment are common. These manifestations generally emerge during childhood or development, although psychiatric and behavioral difficulties may persist into adulthood or become more prominent later in development.

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

  • Microcephaly

  • Prognathism

  • Widely spaced eyes

  • Synophrys

  • Short nose

  • Downturned corners of mouth

Other characteristic features include childhood hypotonia, seizures/epilepsy, and hearing and visual abnormalities. Neurologic manifestations may include structural brain abnormalities, including abnormalities of the corpus callosum and white matter. Additional reported features include congenital heart defects, renal and urologic abnormalities, genital abnormalities in males, obesity, severe respiratory infections, feeding difficulties, gastroesophageal reflux, skeletal abnormalities, and dental abnormalities.

Early diagnosis is important to identify and monitor potentially serious neurologic, cardiac, renal, and respiratory 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.