X-linked deafness-4 is a nonsyndromic form of progressive hearing loss with postlingual onset. Affected males show earlier onset of hearing loss than affected females (summary by del Castillo et al., 1996).
Del Castillo et al. (1996) reported a Spanish family affected by a previously undescribed X-linked form of hearing impairment. Deafness in this family was nonsyndromic, sensorineural, and progressive. In affected males, the auditory impairment was first detected at ... Del Castillo et al. (1996) reported a Spanish family affected by a previously undescribed X-linked form of hearing impairment. Deafness in this family was nonsyndromic, sensorineural, and progressive. In affected males, the auditory impairment was first detected at school age (5-7 years), and it affected mainly high-frequency hearing. It later evolved to become severe to profound and affected all frequencies. Carrier females manifested moderate hearing impairment in the high frequencies with onset in the fourth decade of life. Schraders et al. (2011) reported a large 5-generation family of Dutch origin with postlingual progressive hearing impairment showing an X-linked pattern of inheritance. Hearing impairment developed earlier and was more severe in males than in females: it was first noticed between ages 2 and 10 years in males (mean of 3.3 years) and between 3 and 48 years in females (mean of 28.2 years). In males, the largest decrease in hearing occurred in the first 2 decades. Hearing impairment in females exhibited a large variation in severity. Abdelfatah et al. (2013) reported 2 large, multigenerational families from Newfoundland with DFNX4. Males with the mutation developed progressive, severe bilateral sensorineural deafness affecting all frequencies. It was usually of prelingual onset, but not necessarily present from birth, as at least 2 males had onset in the first decade and had difficulties in school. Female mutation carriers showed a variable phenotype, some with early-onset hearing loss and others with later-onset hearing loss. None of the mutation carriers had muscle weakness.
In 2 unrelated families with X-linked deafness-4, including the large Spanish family previously reported by del Castillo et al. (1996), Huebner et al. (2011) identified 2 different truncating mutations in the SMPX gene (300226.0001 and 300226.0002, respectively). Noting ... In 2 unrelated families with X-linked deafness-4, including the large Spanish family previously reported by del Castillo et al. (1996), Huebner et al. (2011) identified 2 different truncating mutations in the SMPX gene (300226.0001 and 300226.0002, respectively). Noting that a characteristic of SMPX is to respond to physical force, the authors suggested that loss of SMPX from the inner ear may render certain cells susceptible to the stress of mechanical challenges innate to the hearing process. Schraders et al. (2011) independently identified 2 more truncating mutations in the SMPX gene (300226.0003 and 300226.0004, respectively) in 2 families with DFNX4. The authors suggested that SMPX functions in the development and/or maintenance of sensory hair cells.
Abdelfatah et al. (2013) identified a truncating mutation in the SMPX gene (99delC; 300226.0005) in affected members of 2 large, multigenerational families from Newfoundland with DFNX4. Haplotype analysis indicated a founder effect.