Walsh & Hoyt: Hereditary Optic Atrophy with Progressive Hearing Loss and Polyneuropathy

Rosenberg and Chutorian reported the occurrence of progressive optic atrophy, sensorineural deafness, and polyneuropathy in three men belonging to two generations of a single family, two brothers and their nephew. The two brothers were 32 and 29 years-old and the nephew was 3.5 years-old when examined. All patients had poor hearing since childhood, with progression to virtually complete deafness. In the two older patients, gait disturbance began between 5 and 10 years of age, and the child had an awkward gait, absent deep tendon reflexes, and a partial Gowers sign. One brother had visual acuity of 20/100 bilaterally with full visual fields and bilateral optic atrophy, temporal more than nasal. The other brother had visual acuity of 20/400 in both eyes with constricted fields and bilateral optic atrophy. The nephew had a normal ophthalmoscopic examination. All three individuals had abnormally slow nerve conduction velocities. The two brothers had gastrocnemius muscle biopsies showing severe neurogenic atrophy, whereas their nephew had a normal muscle biopsy but a sural nerve biopsy showing demyelination with axonal preservation. A similar family was reported by Iwashita et al., consisting of a 25-year-old man and his 15-year-old sister. Both patients had bilateral optic atrophy, although the affected man had visual acuity of 20/100 in each eye while his sister had visual acuity of 20/20. Neurogenic hearing loss was present in both individuals; however, unlike the patients described by Rosenberg and Chutorian, nerve conduction velocities were normal in bothpatients, as were muscle biopsies. A sural nerve biopsy in the affected male showed mild demyelination. Subsequently, Hagemoser et al. reported two families with autosomal-dominant optic atrophy in the first decade of life, followed by the development of hearing loss and peripheral neuropathy. These authors differentiated these families from those of Rosenberg and Chiturian and Iwashita et al. by the severity and early onset of the optic atrophy and by the mode of inheritance. Hagemoser et al. suggested that the Rosenberg and Chiturian pedigree represents an X-linked disorder and the Iwashita et al. family an autosomal-recessive disorder. These disorders can be included in the spectrum of hereditary polyneuropathies that includes Charcot-Marie-Tooth disease.