orofaciodigital syndrome type 1
MIM.311200 Xp22.3-p22.2
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.
Synopsis
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
Etiology
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.
References
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