Temporal bone histopathologic and genetic studies in Mohr-Tranebj rg syndrome (DFN-1)

Objective: To describe the temporal bone histopathologic and genetic abnormalities in a case of Mohr-Tranebjaerg syndrome Background: Mohr-Tranebjaerg syndrome (DFN-I) is an X-linked, recessive, syndromic hearing loss, characterized by postlingual sensorineural hearing loss with onset in childhood, followed in adult life by progressive dystonia, spasticity, dysphagia, and optic atrophy. The syndrome is caused by mutations in the DDP (deafness/dystonia peptide) gene, which are thought to result in mitochondrial dysfunction with subsequent neurodegeneration. The temporal bone pathologic changes in this syndrome have not been reported. Methods: Hearing loss developed in the patient at age 4, blindness at age 48, and dystonia at age 57. Genetic studies on peripheral blood showed a 151delT mutation in his DDP gene. He died at age 66. The right temporal bone was subjected to Light microscopy and polymerase chain reaction-based analysis of the DDP gene sequence. Results: There was near complete loss of spiral ganglion cells with loss of nearly all peripheral and central processes. Only 1,765 spiral ganglion cells remained (8.5% of mean normal far age). The organ of Corti (including hair cells), stria vascularis, and spiral ligament were preserved. There was also a severe loss of Scarpa's ganglion cells with preservation of vestibular hair cells. The population of geniculate and trigeminal ganglion cells appeared normal. Sequence analysis from temporal bone DNA showed the 151delT DDP gene mutation. Conclusion: Sensorineural hearing loss in Mohr-Tranebjaerg syndrome is the result of a postnatal, progressive, severe auditory neuropathy.