Retinol dehydrogenase 12 (RDH12) is a small gene located on chromosome 14, encoding an enzyme capable of metabolizing retinoids. It is primarily located in photoreceptor inner segments and thereby is believed to have an important role in clearing excessive retinal and other toxic aldehydes produced by light exposure. Clinical features: RDH12-associated retinopathy has wide phenotypic variability; including early-onset severe retinal dystrophy/Leber Congenital Amaurosis (EOSRD/LCA; most frequent presentation), retinitis pigmentosa, cone-rod dystrophy, and macular dystrophy. It can be inherited in an autosomal recessive and dominant fashion. RDH12-EOSRD/LCA's key features are early visual impairment, petal-shaped, coloboma-like macular atrophy with variegated watercolour-like pattern, peripapillary sparing, and often dense bone spicule pigmentation. Future directions: There is currently no treatment available for RDH12-retinopathy. However, extensive preclinical investigations and an ongoing prospective natural history study are preparing the necessary foundation to design and establish forthcoming clinical trials. Herein, we will concisely review pathophysiology, molecular genetics, clinical features, and discuss therapeutic approaches.
Keywords: LCA; RDH12; early onset severe retinal dystrophy; gene therapy; molecular genetics; retinal dystrophy.