Microphthalmia, Syndromic 11

A number sign (#) is used with this entry because of evidence that microphthalmia associated with cleft lip and palate and agenesis of the corpus callosum (MCOPS11) is caused by homozygous mutation in the VAX1 gene (604294) on chromosome 10q25. One such patient has been reported.

Clinical Features

Slavotinek et al. (2012) studied an Egyptian boy, born of consanguineous parents, in whom bilateral severe microphthalmia and bilateral cleft lip and palate were noted at birth. At age 4 months, his development was delayed, he had no head control, and his anterior fontanel was open. Chest, heart, abdomen, genitalia, skeletal system, skin, and muscle tone were unremarkable, and hearing was reported to be normal. At 3.5 years of age, weight, height, and head circumference were at the 3rd centile, and he had global developmental delay, with a developmental level of 6 months. MRI of the brain revealed absence of normal ocular globes bilaterally, with a fluid-filled cyst in the right orbit, and small optic nerves. The corpus callosum and pineal gland were absent, and the hippocampus had a vertical orientation. The parents had no obvious eye malformations, and there was an unaffected sib.

Molecular Genetics

Slavotinek et al. (2012) sequenced the candidate genes VAX1 (604294) and VAX2 (604295) in 70 patients with clinical anophthalmia/microphthalmia and identified homozygosity for a VAX1 missense mutation (R152S; 604294.0001) in an Egyptian boy with bilateral severe microphthalmia and small optic nerves, bilateral cleft lip and palate, and agenesis of the corpus callosum. Slavotinek et al. (2012) then analyzed the VAX1 gene in an additional 10 patients with clinical anophthalmia/microphthalmia and at least 1 additional finding of cleft palate and/or agenesis of the corpus callosum, but found only 1 heterozygous silent substitution of unclear significance.