17q21 microdeletion syndrome (Koolen-de Vries 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.

17q21 microdeletion syndrome (Koolen-de Vries syndrome) is a rare genetic disorder caused by deletion of a small part of the long arm of chromosome 17. 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. A distinctive presentation may include the combination of a long face, upslanted palpebral fissures, and protruding ears.

It can present with psychiatric features such as ADHD, anxiety, autism spectrum disorder (ASD), stereotypic or repetitive behaviors, and behavioral dysregulation. Depression and psychotic symptoms have also been reported, although these are less characteristic. A typically friendly, sociable, and cooperative disposition is common and may be a useful behavioral clue. Cognitive impairment, developmental delay, and particularly marked speech and language impairment are common. These manifestations generally emerge during childhood or development, although anxiety, behavioral difficulties, and other neuropsychiatric manifestations may persist into adulthood or become more prominent later in development.

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

  • Macrocephaly

  • Prominent forehead

  • Epicanthus

  • Upslanted palpebral fissures

  • Ptosis

  • Low-set ears

  • Protruding ears

  • Long fingers

  • Prominent fingertip pads

Other characteristic features include hypotonia, seizures/epilepsy, and structural brain abnormalities, including abnormalities of the corpus callosum and, in some individuals, Chiari malformation. Ophthalmologic features may include strabismus, hypermetropia, congenital cataracts, and optic atrophy, while hearing impairment may also occur. Additional reported features include congenital heart defects, renal and urologic abnormalities, feeding difficulties, joint hypermobility, scoliosis, and tracheo-/laryngomalacia.

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