Craniofacial Anomalies And Anterior Segment Dysgenesis Syndrome

A number sign (#) is used with this entry because of evidence that craniofacial anomalies and anterior segment dysgenesis syndrome is caused by heterozygous mutation in the VSX1 gene (605020) on chromosome 20p11. One such family has been reported.

Clinical Features

Mintz-Hittner et al. (2004) studied 7 members of a 3-generation African American family, 4 of whom had abnormal craniofacial features and anterior segment developmental anomalies. Clinical features demonstrated extremely variable expressivity, but all affected individuals had wide interpupillary distance, abnormal corneal endothelium, and unusual pinnae. Other features included partially to completely empty sella turcica, posterior fossa cyst, anterior encephalocele, and/or hydrocephalus. Electrophysiologic examination provided evidence for abnormal cone bipolar cells (on visual evoked response and electroretinogram) in affected adult patients and for abnormal auditory bipolar cells (on audiogram and audio-evoked brainstem response) in the propositus.

Molecular Genetics

In affected members of an African American family with abnormal craniofacial features and anterior segment developmental anomalies, Mintz-Hittner et al. (2004) found a heterozygous G-to-T transversion at codon 256 in the CVC domain of the VSX1 protein that resulted in a change of an alanine to serine (A256S; 605020.0004). The A256S mutation segregated with the 4 patients and was not found in 624 control chromosomes.