Sensorineural hearing loss in OPA1-linked disorders

ARTICLE Sir, We have read with interest the article by Yu-Wai-Man et al. (2010) reporting heterogeneous multi-system manifestations in 104 patients affected with autosomal dominant optic atrophy (DOA) caused by mutations in the nuclear gene encoding the mitochondrial OPA1 protein. Yu-Wai-Man et al. (2010) found that ∼20% of the OPA1 mutation carriers had complicated forms of dominant optic atrophy, the so-called ‘DOA+’ forms, associating extra-ocular features such as hearing loss or neuromuscular disorders similar to those observed in mitochondrial oxidative phosphorylation defects or in syndromes with mitochondrial DNA instability (Amati-Bonneau et al. , 2008; Hudson et al. , 2008; Yu-Wai-Man et al. , 2010). Interestingly, Yu-Wai-Man et al. (2010) report that sensorineural hearing loss, the most frequent extra-ocular manifestation in ‘DOA+’, occurred in nearly two-thirds of their patients. To characterize the prevalence and the type of hearing loss in OPA1 mutation carriers, we retrospectively reviewed the files of 1380 patients affected with hereditary optic neuropathies referred to our laboratory from 2003 to 2011 for molecular diagnosis. During this period, an OPA1 mutation was identified in 327 patients (24%), 21 of whom (6.4%) had hearing impairment. Clinical information about these 21 patients was obtained from 13 departments of ophthalmology, ENT and medical genetics (12 in France, one in Denmark) (Table 1). All patients had undergone standard pure-tone air and bone conduction audiometry (125–8000 Hz), and speech audiometry had been performed in eight patients. Results of auditory brainstem responses and otoacoustic emission testing were available for only eight patients (Table 2). View this table: Table 1 Clinical and molecular findings in 21 OPA1 mutation carriers affected with optic atrophy and hearing loss View this table: Table 2 Audiological data from 10 OPA1 mutation carriers The 21 OPA1 mutation carriers with hearing loss (11 females and 10 males) belonged to 13 families and were aged from 12 to 73 years …