OMIM ID:
Anterior Segment, Brain, and Facial Anomalies
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
The interpupillary distance appears abnormally wide. VEP and ERG responses suggest abnormal retinal bipolar cells. Specular microscopy reveals variable sizes and shapes of corneal endothelial cells with scattered vesicles and large ‘holes’ in the usual hexagonal array. The iris may be malformed (no collarette, stromal hypoplasia) and there may be peripheral iridocorneal adhesions. Elevated IOP, band keratopathy, corneal clouding, and keratoconus have been reported. Visual acuity is impaired to some extent, from near normal (20/25) to NLP. Progressive optic atrophy was observed in one patient.
Systemic Features
Four members of a 3 generation family had malformed pinnae (posterior placement and rotation). Other features variably present were an empty sella turcica, posterior fossa cyst, and hydrocephalus. The propositus also was found to have abnormal auditory bipolar cells based on the audiogram and audio-evoked brainstem responses.
Genetics
Inheritance
Based on direct sequencing in one family (3 adults and 1 child), this condition seems to be caused by heterozygous variations or mutations in the VSX1 gene (20p11.21).
Pedigree
Autosomal dominant
Autosomal dominant disorders require only one mutation for the disease to be expressed. Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease. It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).
Autosomal dominant inheritance leads to a vertical pattern of transmission