Clinical Characteristics
Ocular Features
The most consistent feature associated with mutations in the VSX2 gene is, of course, microphthalmia/anophthalmia. Other anomalies include dysplasia of the retina, cataracts and/or dislocated lenses, and iris anomalies ranging from hypoplasia to colobomas and absence of the pupils. Colobomas may also involve the posterior uveal tract as well as the optic nerve. The majority of patients are blind.
Systemic Features
No systemic features are associated.
Genetics
Inheritance
This is an autosomal recessive disorder resulting from mutations in the VSX2 (formerly CHX10) gene located at 14q24.3. The gene is expressed in progenitor cells of the developing neuroretina and in inner nuclear cells of the adult retina. Most parents are consanguineous.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.