Walsh & Hoyt: Apparent Sex-Linked Optic Atrophy

In 1975, Went et al. reported a three-generation family with eight individuals with optic atrophy, all male and all related via the maternal lineage. The onset of visual loss was inearly childhood, never acutely, with very slow progression. Visual acuities ranged from 20/50 to 20/1200. Visual evoked potentials showed prolonged latencies, and an ERG of the proband showed no abnormalities. One of the affected males had neurologic abnormalities, including ataxia, tremor, absent ankle jerks, and mental retardation. Subtle neurologic abnormalities were noted in the other males with optic atrophy, including absent ankle jerks, plantar responses, mild tremor, and gait disturbances. One branch of the pedigree had Huntingtons disease, presumably coincidentally. This family has subsequently been found to show close linkage to the Xp11.411.2 region of the X chromosome and not to harbor any of the common primary mtDNA mutations associated with LHON. Another family described by Lysen and Oliver demonstrated transmissionfrom anaffected grandfather to his grandson through an unaffected daughter, thereby strengthening the argument for sex-linked transmission. However, the documentation of optic atrophy was uncertain, and some affected individuals apparently had evidence of chorioretinitis