Hereditary optic neuropathies.

Abstract

The hereditary optic neuropathies comprise a group of disorders in which the cause of optic nerve dysfunction appears to be inheritable, as demonstrated or suggested by familial expression or genetic analysis. Clinical variability, both within and among families with the same disease, often makes recognition and classification difficult. Genetic analysis now permits diagnosis of some of the hereditary optic neuropathies in the absence of family history or in the setting of unusual clinical presentation^.^^,^^ The inherited optic neuropathies typically manifest as symmetric, bilateral, painless, central visual loss. In many of these disorders, the papillomacular nerve fiber bundle is affected, with resultant central or cecocentral scotomas. The exact location of initial pathology along the ganglion cell and its axon, and the pathophysiologic mechanisms of optic nerve injury remain unknown. Optic nerve damage is usually permanent and, in many diseases, may be progressive. Once optic atrophy is observed, substantial nerve injury has already occ~rred.~~,~~ In classifying the hereditary optic neuropathies, it is important to exclude the primary This article was adapted from Newman NJ. Hereditary optic neuropathies. In Miller NR, Newman NJ (eds). Walsh & Hoyt Clinical Neuro-Ophthalmology, vol 1 (ed 5). Baltimore, Williams & Wilkins, 1999, pp 741-773, with permission. retinal degenerations that may masquerade as primary optic neuropathies because of the common finding of optic disc pallor. Retinal findings may be subtle, especially among the cone dystrophies, where optic nerve pallor may be an early finding. The possibility of a primary retinal process should be considered in patients with temporal optic atrophy, even when the retina itself is not obviously abnormal. Retinal arterial attenuation and abnormal electroretinography should help distinguish these diseases from the primary optic neuropathies. However, optic nerve disease and retinal pathology may also coexist. Among the multi-system disorders (see below) primary retinal degeneration with secondary optic disc pallor is a frequent occurrence and may be difficult to distinguish from primary optic nerve involvement. At times there may be co-existent pathology. Customary classification of the inherited optic neuropathies is by pattern of transmission. The most common patterns of inheritance include autosomal dominant, autosomal recessive, and maternal (mitochondrial). The same genetic defect may not be responsible for all pedigrees with optic neuropathy inherited in a similar fashion. Similarly, different genetic defects may cause identical or similar phenotypes, some inherited in the same manner, others not. Alternatively, the same genetic defect may result in different clinical expression,