DOA, Wolfram, Is it All the Same? (PDF)

Amongst the many causes of optic neuropathies, the inherited optic neuropathies are figuring more commonly in the differential diagnosis of otherwise unexplained optic atrophy, despite there often being no recognized family history. While in the past this diagnosis was often one of exclusion or presumption, modern advances in the detection of genetic abnormalities in both the nuclear and mitochondrial genomes have allowed for a veritable revolution in the genetic diagnosis of inherited causes of optic nerve disease (1-3). Linkage analysis requiring large pedigrees and clinical syndrome recognition, although still often important to alert the astute clinician that a disorder might be genetic and prompt appropriate testing, have largely yielded to strategies that go even beyond targeted gene sequencing to gene panel screening with next generation sequencing (NGS) (1). As accessibility increases, costs decrease, and these tests are becoming more frequently used in routine neuroophthalmologic practice.