Orofaciodigital Syndrome Xv

A number sign (#) is used with this entry because of evidence that orofaciodigital syndrome XV (OFD15) is caused by compound heterozygous mutation in the KIAA0753 gene (617112) on chromosome 17p13. One such patient has been reported.

Clinical Features

Chevrier et al. (2016) studied a female infant who was born with facial dysmorphism, lobulated tongue, clefting of the alveolar ridges, left hand postaxial polydactyly, broad right hallux and left hallux duplication, and intermittent respiratory difficulty. Brain MRI showed multiple anomalies, including vermis hypoplasia with molar tooth sign (MTS), agenesis of corpus callosum, and ventricular dilation. Abdominal ultrasound revealed bilateral hydronephrosis. Because of the association of oral defects, polydactyly, and MTS, the authors designated the clinical classification of this patient as orofaciodigital syndrome type VI (OFD6; see 277170).

Molecular Genetics

By exome sequencing in a female infant with orofaciodigital syndrome, Chevrier et al. (2016) identified compound heterozygosity for a nonsense mutation (K631X; 617112.0001) and a splice site mutation (617112.0002) in the KIAA0753 gene. Her unaffected mother carried the nonsense mutation, but the splice mutation occurred de novo. Analysis of KIAA0753 in 32 patients diagnosed with either OFD6 or Joubert syndrome (see 213300) did not reveal any additional mutations.