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

Objective: To describe the temporal bone histopathologic and genetic abnorm alities in a case of Mohr-Tranebjaerg syndrome Background: Mohr-Tranebjaerg syndrome (DFN-I) is an X-linked, recessive, sy ndromic hearing loss, characterized by postlingual sensorineural hearing lo ss with onset in childhood, followed in adult life by progressive dystonia, spasticity, dysphagia, and optic atrophy. The syndrome is caused by mutati ons in the DDP (deafness/dystonia peptide) gene, which are thought to resul t in mitochondrial dysfunction with subsequent neurodegeneration. The tempo ral bone pathologic changes in this syndrome have not been reported. Methods: Hearing loss developed in the patient at age 4, blindness at age 4 8, and dystonia at age 57. Genetic studies on peripheral blood showed a 151 delT mutation in his DDP gene. He died at age 66. The right temporal bone w as subjected to Light microscopy and polymerase chain reaction-based analys is 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 ce lls remained (8.5% of mean normal far age). The organ of Corti (including h air cells), stria vascularis, and spiral ligament were preserved. There was also a severe loss of Scarpa's ganglion cells with preservation of vestibu lar hair cells. The population of geniculate and trigeminal ganglion cells appeared normal. Sequence analysis from temporal bone DNA showed the 151del T DDP gene mutation. Conclusion: Sensorineural hearing loss in Mohr-Tranebjaerg syndrome is the result of a postnatal, progressive, severe auditory neuropathy.