Clinical Domain Working Groups

Pediatric cataracts affect 20,000-40,000 children each year worldwide. Cataract may be an isolated finding or seen in association with one of more than 200 syndromes. Identification of the underlying genetic etiology of pediatric cataracts may clarify associated health risks, aid in prognostication, and guide medical management and family planning. Early identification of a genetic etiology can have a significant impact, such as for those with cerebrotendinous xanthomatosis, a rare lipid storage disease in which early treatment can slow or even stop disease progression. Accordingly, a missed diagnosis can delay necessary screening or treatment, potentially increasing disease morbidity and deceasing quality of life for individuals with pediatric cataracts. We hypothesize that there will be fewer missed diagnoses and improved clinical outcomes if we develop gene-specific variant classification guidelines for clinically actionable pediatric cataracts.

We therefore propose a Pediatric Cataract VCEP. We plan to begin with 4 genes associated with systemic manifestations where pediatric cataracts may be the presenting symptom of a syndrome with treatment/screening recommendations in the following order: 1. CYP27A1, 2. OCRL, 2. MAF, and 4. FTL.

Prior to transitioning work to OCRL, we will invite additional members to join the VCEP with expertise in Lowe syndrome. Additionally, MAF and FTL will undergo gene curation through the Glaucoma and Neuro-Ophthalmology GCEPs prior to our VCEP work on these genes. Both have agreed to complete this work in accordance with our anticipated timeline.