LETTER TO JMG Four novel mutations in the OFD1 (Cxorf5) gene in Finnish patients with oral-facial-digital syndrome 1

Oral-facial-digital syndrome type 1 (OFD1, MIM 311200) was first described by Papillon-Léage and Psaume in 1954 and further delineated in 1962 by Gorlin and Psaume, who called it orodigitofacial dysostosis. It is a multiple congenital anomaly syndrome characterised by malformations of the face, oral cavity, and hands and feet. The facial dysmorphic features include hypertelorism, frontal bossing, broad nasal bridge, hypoplasia of alar cartilage, and transient milia. Oral cavity malformations include often asymmetrical cleft of the palate (80%), small midline cleft of the upper lip (45%), clefts of the tongue, hamartomatous masses on the ventral surface of the tongue (70%), mucobuccal fibrous bands, and dental abnormalities. Malformations of the fingers are seen in 50-70% and toe malformations in 25%. Central nervous system abnormalities, such as hydrocephalus, porencephaly, and agenesis of the corpus callosum, with mild mental retardation are seen in 40%. In recent years, a kidney disease closely resembling adult type polycystic kidney disease has been shown to be one of the distinct features of this syndrome. 5 At least nine different forms of oral-facial-digital syndromes have been described, type 1 being the most common with a suggested incidence of 1:50 000 live births. OFD1 syndrome has dominant X linked inheritance with lethality in males. However, a case of Klinefelter syndrome (XXY) with OFD1 has been reported. By linkage analysis in two kindreds, the locus for OFD1 was mapped to Xp22.3-22.2. Recently, the gene for OFD1, Cxorf5, was identified, and mutations of three familial and four sporadic cases were identified by Ferrante et al. Expression of the gene was seen in all the tissues affected in the syndrome. We report here the identification of four novel mutations in the OFD1 gene together with the clinical findings in four Finnish families, of which two are familial and two sporadic.