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orofaciodigital syndrome type 1

MIM.311200 Xp22.3-p22.2

Tuesday 28 February 2006

The oral-facial-digital type I (OFD1) syndrome (MIM.311200) is a X-linked dominant developmental disorder. Affected individuals have craniofacial and digital abnormalities and, in 15% of cases, polycystic kidney. The disease is inherited as an X-linked dominant male-lethal trait.


- short stature
- hearing loss
- telecanthus
- hypertelorism
- hypoplastic alar cartilage
- hyperplastic oral frenuli
- median cleft lip
- lobulated tongue
- bifid tongue
- tongue nodule
- cleft palate
- tongue hamartoma
- highly arched palate
- dental caries
- anomalous anterior teeth
- enamel hypoplasia
- supernumerary teeth
- missing teeth
- adult onset polycystic kidney
- clinodactyly
- syndactyly
- brachydactyly
- unilateral preaxial polydactyly
- milia of upper face and ears (infancy)
- dry scalp
- dry, rough, sparse hair
- alopecia
- variable mental retardation
- absence of corpus callosum
- gray matter heterotopias
- hydrocephalus
- seizures
- hypothalamic hamartoma
- porencephaly


- oral-facial-digital syndrome type I (OFD1) has been found to be caused by mutations in the CXORF5 gene (MIM.300170).

Animal models

- knock-out mice Ofd-/- (16311594)

  • Using a Cre-loxP system, knockout animals were generated lacking Ofd1 and reproduced the main features of the disease, albeit with increased severity, possibly owing to differences of X inactivation patterns between human and mouse.
  • Failure of left-right axis specification were found in mutant male embryos, and ultrastructural analysis showed a lack of cilia in the embryonic node.
  • Formation of cilia was defective in cystic kidneys from heterozygous females, implicating ciliogenesis as a mechanism underlying cyst development.
  • Impaired patterning were found of the neural tube and altered expression of the 5’ Hoxa and Hoxd genes in the limb buds of mice lacking Ofd1, suggesting that Ofd1 could have a role beyond primary cilium organization and assembly.


- Ferrante MI, Zullo A, Barra A, Bimonte S, Messaddeq N, Studer M, Dolle P, Franco B. Oral-facial-digital type I protein is required for primary cilia formation and left-right axis specification. Nat Genet. 2006 Jan;38(1):112-7. PMID: 16311594