54 - Hereditary optic neuropathies

Abstract

Hereditary optic neuropathies are those optic nerve disorders which are expressed along familial lines or are identified on a genetic basis. These disorders can have significant variability in expression, and are most often inherited in autosomal dominant, autosomal recessive, X-linked recessive, or maternal patterns. Mitochondrial dysfunction is often the final common pathway for optic nerve damage in these disorders. Many of these diseases were defined initially by their clinical presentation. However, as more and more patients undergo genetic sequencing to determine a cause for their underlying disease, more pathogenic gene mutations are being identified. This has led to surprising findings as phenotype does not always correlate with genotype, and vice versa. Identifying causative loci has allowed for development of targeted therapies for hereditary optic neuropathies from specific mutations, particularly for Leber hereditary optic neuropathy. The chapter describes the most commonly encountered monosymptomatic hereditary optic neuropathies (Leber hereditary optic neuropathy and dominant optic atrophy) and their potential therapies and goes on to describe other syndromic optic neuropathies and optic neuropathies associated with inherited neurologic disease. Finally, secondary optic neuropathies from other inherited multisystem diseases are described.