NEIi004-A

OPA1-related optic atrophy with or without extraocular features

Any primary mitochondrial disease in which the cause of the disease is monoallelic or biallelic variants in the OPA1 gene. While optic atrophy is present in most affected cases, OPA1 is a mitochondrial protein and thus features of this disease include abnormal mitochondrial morphology and multiple mitochondrial DNA deletions, and can affect other organ systems and. Extraocular features can include progressive sensorineural hearing impairment, cognitive impairment, peripheral neuropathy, myopathy, ragged-red muscle fibers, and exercise-induced lactic acidemia, while additional ocular features can include progressive visual loss, central scotoma, and color vision abnormalities.; Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found the molecular mechanism (loss of function variants in OPA1) to be consistent among apparently unrelated patients, while related patients harboring either biallelic or monoallelic OPA1 variants were affected with optic atrophy. The phenotypic variability between them appeared to represent a spectrum of disease rather than separate disease entities. Therefore, affected cases harboring monoallelic or biallelic OPA1 variants have been lumped into a single disease entity, referred to as OPA1-related optic atrophy with or without extraocular features.