Orofaciodigital Syndrome Xvii

A number sign (#) is used with this entry because of evidence that orofaciodigital syndrome XVII (OFD17) is caused by homozygous mutation in the INTU gene (610621) on chromosome 4q28. One such patient has been reported.

Clinical Features

Panigrahi et al. (2013) described an unrelated Indian girl and boy with overlapping orofaciodigital phenotypes. Both children showed short stature and low weight, prominent forehead and nose, low-set ears with hearing loss, midline cleft lip, and retrognathia. The girl had cleft tongue, dental malocclusion, and multiple oral frenula, whereas the boy had high-arched palate and nodular tongue. Both also exhibited multiple digital anomalies, including bifid thumbs and great toes, short index fingers due to shortening of the middle phalanx, polydactyly of the hands and feet, and a Y-shaped central metacarpal. In addition, the boy had tetralogy of Fallot, bilateral small kidneys, hypomyelination of the corpus callosum, and ventriculomegaly, whereas the girl had normal echocardiography, renal ultrasound, and brain MRI. The boy showed speech delay but otherwise average academic ability, and the girl had global developmental delay with mild learning disability. Chest x-ray in the girl did not show short ribs or narrow chest; these features were not reported for the boy. The authors noted that Y-shaped metacarpal is a characteristic feature of OFD6 (277170), whereas the face and hand abnormalities in the 2 children were suggestive of Mohr syndrome (OFD2; 252100).

Inheritance

The transmission pattern of OFD in the family reported by Toriyama et al. (2016) was consistent with autosomal recessive inheritance.

Molecular Genetics

Toriyama et al. (2016) examined the exomes of patients diagnosed with OFD and identified homozygosity for a 1-bp deletion in the INTU gene (610621.0004) in a 10-year-old Indian boy (case 3) with OFD who was originally reported by Panigrahi et al. (2013). The mutation was present in heterozygosity in his unaffected parents.