Ganglion Cell Diseases

Abstract

Inherited optic neuropathies are diseases of retinal ganglion cell dysfunction or loss which lead to optic atrophy. This group of conditions share many common clinical features, which comprise bilateral, symmetrical, painless reduced visual acuity; colour vision defects; central or centro-caecal visual field loss; and pallor of the optic disc. They are a genetically heterogeneous group of conditions, with autosomal dominant, recessive and X-linked, as well as mitochondrial inheritance. The dominant and mitochondrial forms are the commonest. Table 48.1 shows the seven mapped autosomal loci and five known genes to date. OPA1 is the locus for the so-called Kjer autosomal dominant optic atrophy on chromosome 3q29 (OPA1; MIM: 165500) and is due to mutation in the OPA1 gene. It is also associated with the allelic condition syndromic dominant optic atrophy, DOA + syndrome. X-linked optic atrophy 2, OPA2 (311050), has been mapped to chromosome Xp11.4-p11.21. Optic atrophy 3, or dominant optic atrophy and cataract (OPA3; 165300), is caused by mutation in the OPA3 gene (606580) on chromosome 19q13.2-q13.3. This is allelic to recessive optic atrophy 3 or Costeff syndrome. Optic atrophy 4 (OPA4; 605293) has been mapped to chromosome 18q12.2-q12.3 and optic atrophy 5 (OPA5; 610708) to chromosome 22q12.1-q13.1. Recessive optic atrophy 6 (OPA6; 258500) maps to chromosome 8q. And recessive optic atrophy 7 (OPA7; 612989) is caused by mutation in the TMEM126A gene (612988) on chromosome 11q14.1-q21. Wolfram syndrome 1 (DIDMOAD) is due to mutations in the Wolframin gene, whereas WFS2 is caused by mutation of the CSID2 gene. From this description it is clear that there remain a number of as yet unidentified genes. In addition to the above autosomal optic neuropathies, there is the maternally inherited mitochondrial disease Leber’s hereditary optic neuropathy (LHON), which is due to a primary mutation in the mitochondrial DNA.