Anterior Segment, Brain, and Facial Anomalies

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.


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). 

Treatment Options: 

Monitoring for glaucoma and appropriate treatment are indicated.  Hearing tests should be performed early.  The usual treatments for keratoconus should be considered.  Excess brain fluid may need surgical drainage.


Article Title: 


Mintz-Hittner HA, Semina EV, Frishman LJ, Prager TC, Murray JC. VSX1 (RINX) mutation with craniofacial anomalies, empty sella, corneal endothelial changes, and abnormal retinal and auditory bipolar cells. Ophthalmology. 2004 Apr;111(4):828-36.

PubMedID: 15051220