Phenotype of the first otosclerosis family linked to OTSC10

OBJECTIVES: To report on the audiometric findings in the first otosclerosis family linked to OTSC10. STUDY DESIGN: Retrospective cohort study. METHODS: A family study in a large otosclerosis family was performed, and a pedigree was constructed. Examination of all family members consisted of medical history guided by a questionnaire, pure-tone audiometry, otoscopy, and collection of blood samples for genetic linkage analysis. In addition, a selected group underwent stapedial reflex measurements and tympanometry. Cross-sectional as well as longitudinal analyses of audiometric data were performed. RESULTS: Eleven family members were identified as clinically affected and were all carriers of the disease haplotype. Twelve clinically unaffected family members carried the disease haplotype as well. Cross-sectional analyses of clinically affected family members showed no significant progression of air conduction (AC) thresholds, bone conduction (BC) thresholds, and air-bone gap (ABG) levels with increasing age. Longitudinal regression analyses in one family member revealed significant deterioration of AC thresholds at all frequencies. The BC thresholds showed a significant increase with advancing age at 0.5 kHz, 2 kHz, and 4 kHz. A significant progression of ABG was seen at 8 kHz. CONCLUSIONS: The intersubject variation, in terms of age of onset, level of progression, and audiogram configuration, was remarkable, probably due to reduced penetrance and variable expression of the disease. Long-term audiometric data in one patient, however, were useful to demonstrate progression of hearing impairment