colobomatous optic disc-macular atrophy-chorioretinopathy syndrome

Colobomatous optic disc-macular atrophy-chorioretinopathy syndrome is a rare genetic eye disorder that primarily affects the structure of the optic disc and the macula. It is associated with pathogenic variants in the SIX6 gene, which plays a role in eye development. Affected individuals typically present early in life with visual disturbances such as horizontal nystagmus and poor visual acuity. This condition is extremely rare, affecting fewer than 1 in 1,000,000 people.

The clinical presentation is dominated by distinctive abnormalities in the optic disc, including bilateral colobomatous optic disks and retinal vessels that originate from the peripheral edge of the optic disk, along with macular atrophy. Most individuals exhibit microphthalmia, a feature that is consistently present, while other ocular issues such as buphthalmos, retinal detachment, corneal scarring, glaucoma, chorioretinal coloboma, and iris coloboma occur in a subset of cases. In infancy, patients may be noted to have horizontal nystagmus and decreased visual acuity. Not all individuals experience all features, and severity varies considerably.

The condition is caused by pathogenic variants in the SIX6 gene, which is important for proper eye formation. It is inherited in an autosomal recessive pattern, meaning that an affected individual has received two copies of the pathogenic variant, one from each parent. This condition is more common when parents share a common ancestor, as both are more likely to carry the same rare genetic change. Families are encouraged to seek genetic counseling to better understand the inheritance pattern and recurrence risk, which is 25% for each pregnancy if both parents are carriers.

Currently, management focuses on supportive care and symptom management, as no specific foundational or FDA-approved treatments exist for this condition. A multidisciplinary approach involving ophthalmologists, low vision specialists, and other healthcare professionals is used to address visual impairment and monitor ocular health. Genetic counseling is also recommended to help families understand the implications of the autosomal recessive inheritance pattern and to guide family planning. Treatment is tailored to the individual's needs, and patients should discuss all available options with their healthcare team.

The course of colobomatous optic disc-macular atrophy-chorioretinopathy syndrome is highly variable, with the severity of vision impairment differing among individuals. With current standards of care, many individuals manage their visual challenges into adulthood, though outcomes depend on the extent of ocular involvement and access to supportive interventions. Outcomes described in medical literature continue to evolve as standards of care improve. Families are encouraged to connect with genetic counselors and specialized care teams for personalized guidance and support.