Optic Atrophy 8

Description

Optic atrophy-8 (OPA8) is an autosomal dominant neurologic disorder characterized by progressive visual loss during the first or second decade of life. Some patients may have additional features, mainly late-onset sensorineural hearing loss.

For a discussion of genetic heterogeneity of optic atrophy, see OPA1 (165500).

Clinical Features

Carelli et al. (2011) reported a large multigenerational kindred from the Italian region of Emilia-Romagna in which 53 individuals had with optic neuropathy. Five affected adults were studied in detail. Onset of visual loss occurred between 6 and 21 years of age, and symptoms included central scotoma, diffuse reduction in the retinal nerve fiber layer, and abnormal visual evoked potentials. Electroretinogram was normal in all patients. Two patients had bilateral sensorineural hearing loss for high frequencies, and 3 had abnormal brainstem auditory evoked potentials. Somatosensory evoked potentials were also increased, suggesting some involvement of the dorsal columns. In addition, all 5 patients had mitral valve prolapse or insufficiency. Although mitochondrial integrity and respiratory enzyme analyses were normal, muscle biopsy showed subsarcolemmal accumulations of mitochondria and a slight increase in mtDNA content. Patient fibroblasts grown in galactose medium were unable to increase ATP content compared to controls, and showed an abnormally high rate of fusion activity, suggestive of mitochondrial dysfunction. Ophthalmologic investigations of 11 additional affected family members showed optic atrophy with central scotoma and reduced visual acuity. Carelli et al. (2011) noted that the patients had preferential involvement of the papillomacular bundle with temporal atrophy, which is a typical feature of mitochondrial optic neuropathies.

Inheritance

The transmission pattern of OPA8 in the family reported by Carelli et al. (2011) was consistent with autosomal dominant inheritance.

Mapping

By genomewide linkage analysis of a large Italian kindred with OPA8, Carelli et al. (2011) found significant linkage to a 6.94-cM region on chromosome 16q21-q22 (maximum 2-point lod score of 8.84 at D16S752). Genomic screening of candidate genes in this region did not reveal any mutations.