Investigation of the audiometric characteristics of a large Dutch DFNX4 family with a p.Glu72X mutation in the SMPX gene.Patients and methods:
Sixty family members participated in this study and examination consisted of medical history, otoscopy, pure tone and speech audiometry. Linkage and mutation analysis revealed a pathogenic mutation in the SMPX gene.Results:
All 25 mutation carriers exhibited hearing impairment, except one woman aged 25 years. The men (n = 10) showed more severe hearing impairment than the women (n = 14) and already at a younger age. The age of onset according to history was 2–10 years (mean: 3.3 years) in men and 3–48 years (mean: 26.4 years) in women. In the men, severe threshold deterioration mainly occurred during the first two decades of life, especially at the higher frequencies. The women showed milder threshold deterioration and more pronounced across-subjects and individual inter-aural variation, especially at 2–8 kHz. Longitudinal linear regression analysis demonstrated significant progression of at least two frequencies in five individuals (3 men and 2 women).Results:
The speech recognition scores of the mutation carriers with hearing impairment were decreased at relatively young ages compared to a reference group of patients with only presbycusis, especially in men. However, all these patients tended to have better speech recognition scores than the presbycusis patients at matching PTA1,2,4 kHz levels.Conclusion:
This study demonstrates the phenotypic heterogeneity in this large family with an X-linked pattern of inherited sensorineural hearing impairment. The men showed more severe hearing impairment at a younger age with more pronounced progression during the first two decades of life, while women demonstrated less severe hearing impairment with more gradual progression and a wider variation in age of onset, degree of hearing impairment and inter-aural asymmetry in thresholds.