Oral-facial–digital syndrome (OFD syndrome, type I)

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.

Oral-facial-digital syndrome type I (OFD syndrome type I, OFD1) is an X-linked genetic condition. It can occur as an inherited or de novo genetic condition, so absence of a relevant family history does not exclude the diagnosis. It occurs almost exclusively in females because the condition is usually lethal in males during gestation. A distinctive presentation may include the combination of accessory oral frenula, underdeveloped alae nasi, and digital asymmetry.

It can present with psychiatric features such as ADHD, autism spectrum disorder (ASD), behavioural difficulties, and intellectual or learning disability. These neurobehavioural features are generally recognised during childhood or development, and there is limited evidence for new-onset psychiatric presentations in adulthood.

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

  • Short neck

  • Micrognathia

  • Telecanthus

  • Underdeveloped alae nasi

  • Short philtrum

  • Accessory oral frenula

  • Cleft palate (including submucous cleft palate)

  • Bifid tongue

  • Brachydactyly

  • Syndactyly

Other characteristic features include structural brain abnormalities such as intracerebral cysts, agenesis of the corpus callosum, and cerebellar abnormalities, which may be associated with seizures or ataxia. Intellectual or learning disability occurs in approximately half of affected individuals. Renal cystic disease is common and may become clinically significant in adulthood. Other features may include hearing impairment, milia, and cystic disease affecting the liver, pancreas, or ovaries.

Early diagnosis is important to identify neurological and developmental complications, detect renal cystic disease and other potentially progressive organ involvement, guide appropriate developmental, behavioural, hearing, and educational support, and allow surveillance and management of seizures and kidney disease.

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.