OPA1 and External ophthalmoplegia: ADOA has been known to be associated with sensorineural deafness as occasional co-occurring feature [134], but in 2008 an unexpected observation was reported, that missense heterozygous OPA1 mutations affecting the GTPase domain could lead to a multisystem disorder characterized by chronic progressive external ophthalmolplegia (CPEO), peripheral neuropathy, sensorineural deafness, cerebellar atrophy, white matter lesions and myopathy with RRF due to accumulation of mtDNA multiple deletions, providing a mechanistic link of OPA1 with mtDNA maintenance disorders [135,136].