Xq distal duplication or disomy (Xq27-q28 terminal duplications including MECP2 duplication)

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.

Xq distal duplication or disomy (Xq27-q28 terminal duplications, including MECP2 duplication) is a rare genetic disorder caused by duplication of part of the distal long arm of the X chromosome. Xq distal duplications are a heterogeneous group, and clinical features vary according to the size and location of the duplicated region; the phenotype associated with MECP2 duplication is particularly well characterized and accounts for much of the recognized neuropsychiatric phenotype. It can occur as an inherited or de novo genetic condition, so absence of a relevant family history does not exclude the diagnosis. Most reported MECP2 duplications are inherited, although de novo cases can occur. It predominantly affects males in the MECP2 duplication phenotype, while females may have milder or variable manifestations related in part to X-chromosome inactivation. A distinctive presentation may include the combination of severe intellectual disability, autism spectrum disorder (ASD), mild facial abnormalities, and recurrent infections.

It can present with psychiatric features such as ASD, ADHD, anxiety, stereotypic behaviors, and behavioral dysregulation. Cognitive impairment, developmental delay, and severe speech and language impairment are common, particularly in males with MECP2 duplication. Behavioral and neuropsychiatric manifestations generally emerge during childhood or development, although anxiety, autistic features, and other neuropsychiatric difficulties may persist into adulthood.

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

  • Flat occiput

  • Midface retrusion

  • Widely spaced eyes

  • Epicanthus

  • Depressed nasal bridge

Other characteristic features include hypotonia, seizures/epilepsy, progressive spasticity, and recurrent respiratory infections. Neurologic manifestations may include structural brain abnormalities, including abnormalities of the corpus callosum, white matter, and cerebellum. Additional reported features include feeding difficulties, gastroesophageal reflux, constipation, urogenital abnormalities, hearing and visual abnormalities, and mottled skin.

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