Temporal bone histopathology in cockayne syndrome

Cockayne syndrome (CS) is a rare autosomal recessive syndrome resulting in defective DNA repair. Its features include cachectic dwarfism, hearing loss, skin hypersensitivity to sunlight, premature aging, and dementia. Presented is a right temporal bone of a patient who died at the age of 29 years. The clinical course was compatible with type 1 CS, the classical form. Homozygous missense variant in the ERCC6 gene (Excision Repair Cross-Complementation group 6) was found, compatible with CS complementation group B. Five years before his death he complained of tinnitus. An audiogram 3 and a 1/2 years before his death demonstrated a moderate symmetrical sensorineural hearing loss at 2 to 8 kHz. The speech reception threshold was 20 dB, and the word recognition score was 100% on the right. Histopathology revealed a near normal population of inner hair cells except in the basal 5 mm of the cochlea, and mild loss of outer hair cells particularly at the base of the cochlea. Severe atrophy of the spiral ligament and atrophy of stria vascularis and spiral prominence was present. There was loss of Claudius cells, outer sulcus cells, and mesenchymal cells on the scala tympani side of the basilar membrane and loss of cellularity of the limbus. There was a moderate loss of Scarpa's and spiral ganglion neurons, with the most severe loss in the basal segment. The vestibular neuro-epithelium was nearly intact, with the exception of mild loss in the saccule. The vestibular perilymphatic, and to a lesser extent endolymphatic spaces, were filled with filamentous material and osteoid. The patient had better hearing and a larger complement of neurons compared with the few published case reports. Neurodegenerative symptoms are likely attributed to the effect of intramitochondrial reactive oxygen species. The pathogenesis of hearing loss in CS may shed light on other causes of hearing loss, such as that induced by noise.