Cornelia de Lange syndrome (Brachmann-de Lange 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.

Cornelia de Lange syndrome (Brachmann-de Lange syndrome) is a rare genetic disorder characterized by a distinctive facial appearance, developmental and intellectual impairment, growth restriction, hypertrichosis, and variable limb abnormalities. It can occur as an inherited or de novo genetic condition, so absence of a relevant family history does not exclude the diagnosis. The inheritance pattern varies according to the underlying genetic cause, with both autosomal dominant and X-linked forms recognized. A distinctive presentation may include the combination of synophrys, thin downturning upper lip, and micromelia.

It can present with psychiatric features such as autism spectrum disorder (ASD), ADHD, anxiety, repetitive or stereotypic behaviors, compulsive behaviors, and behavioral dysregulation. Self-injurious behavior is particularly characteristic and may include hand-directed self-injury, biting, or skin picking. Sleep difficulties and sensory-processing difficulties are also common. Cognitive impairment, developmental delay, and speech and language impairment are common, with expressive language often more impaired than receptive language. These manifestations generally emerge during childhood or development, although anxiety, repetitive behaviors, self-injury, and other neurobehavioral difficulties may persist into adulthood and require ongoing assessment and support.

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

  • Microcephaly

  • Midface retrusion

  • Micrognathia

  • Synophrys

  • Long eyelashes

  • Short nose

  • Smooth philtrum

  • Long philtrum

  • Downturned corners of mouth

  • Widely spaced teeth

  • Syndactyly (2nd and 3rd toes)

  • Clinodactyly of fifth fingers

  • Single transverse palmar crease

Other characteristic features include hypertrichosis, hypotonia, seizures/epilepsy, and upper-limb abnormalities, including radioulnar synostosis, oligodactyly, and more severe limb-reduction defects. Other reported features include gastroesophageal reflux and other gastrointestinal abnormalities, feeding difficulties, congenital heart defects, hearing impairment, ophthalmologic abnormalities, genitourinary abnormalities, dental abnormalities, and scoliosis.

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