Orofaciodigital Syndrome Ix

Clinical Features

Gurrieri et al. (1992) described 2 brothers with an orofaciodigital syndrome which did not seem to fit into any of the 7 previously described types (Toriello, 1988; Munke et al., 1990). The 2 brothers were mildly mentally retarded. Both showed a small notch in the upper lip. The older brother had a highly arched palate with bifid tongue and a supernumerary lower canine bilaterally. The younger brother had a lobulated, hamartomatous tongue, and multiple frenula. The specific retinal abnormalities in the brothers reported by Gurrieri et al. (1992) were retinochoroidal lacunae of colobomatous type, similar to those seen in Aicardi syndrome (304050).

Nevin et al. (1994) reported a female case of OFDS with component manifestations typical of type II (252100), namely median cleft of the upper lip, multiple oral frenula, and lobulated or hamartomatous tongue, associated with retinal abnormalities as distinguishing feature. They referred to the disorder as OFDS type IX.

Sigaudy et al. (1996) reported the case of a 6-month-old girl with OFD anomalies associated with areas of chorioretinal atrophy. The parents were nonconsanguineous; the maternal and paternal ages at her birth were 33 and 41 years, respectively. She showed multiple hamartomas of the oral cavity, lobulated tongue, alveolar frenula, and a small median cleft of the upper lip. The great toes were broad. Psychomotor development was delayed. CT scan showed atrophy of the frontal and parietal lobes and NMR showed a hypothalamic hamartoma.

Nagai et al. (1998) described an affected female with features consistent with OFDS IX who was also noted to have Dandy-Walker malformation and retrobulbar cysts.

Erickson and Bodensteiner (2007) described 2 pairs of sibs (2 females, and 1 female and 1 male) from the Navajo population with orofaciodigital syndrome. In addition to retinal colobomas and mild digital anomalies, the sibs also had severe microcephaly, mental retardation, and short stature. Erickson and Bodensteiner (2007) suggested that this condition is a variant of OFDS IX caused by a unique allele of increased frequency in the Navajo population.

Inheritance

Based on their report of affected males, Gurrieri et al. (1992) recognized that inheritance of OFDS IX might be either autosomal or X-linked recessive.

Nevin et al. (1994) suggested that OFDS IX is inherited in an autosomal recessive manner since their reported patient was female.

Erickson and Bodensteiner (2007) also supported autosomal recessive inheritance based on the finding of the disorder in sibs from the Navajo population, which has undergone several genetic 'bottlenecks.'

Molecular Genetics

For discussion of a possible relationship between variation in the TBC1D32 gene and orofaciodigital syndrome IX, see 615867.0001.

For discussion of a possible relationship between variation in the SCLT1 gene and orofaciodigital syndrome IX, see 611399.0001.