Inherited deafness in childhood—the genetic revolution unmasks the clinical challenge

Approximately one child per 1000 is diagnosed with severe, profound, or early onset hearing impairment, of whom approximately 50% are thought to have a genetic cause.1 2 Associated clinical findings, if present and recognised neonatally, often facilitate the identification of a syndrome and the prediction that a hearing problem is likely to be part of the clinical profile. While the presence of such findings affords the recognition of an underlying syndromic diagnosis in up to 30% of hearing impaired individuals, in most children with hearing impairment there are no other clinical findings—that is, the hearing loss is non-syndromic. As most such cases are transmitted in autosomal recessive manner,3 the finding of hearing loss in the affected child is unexpected, often delayed and, in addition to the obvious social and educational implications, frequently accompanied by parental anxiety for subsequent born siblings or ongoing pregnancies. Faced with such clinical tensions, the paediatrician may rightly wonder whether the recent molecular advances in the genetics of deafness might not benefit hearing impaired patients and their families. It is scarcely credible now to recall that less than 10 years ago genetic loci for different forms of hearing loss were just starting to be mapped—initially concentrating on well defined syndromic forms of deafness.4 Though apt to rapid change, reflecting new advances, the situation in September 1999 identified 31 loci for autosomal dominant non-syndromic forms of hearing loss, designated DFNA 1–31, 28 loci for autosomal recessive forms, designated DFNB 1–28, and six loci for X linked forms, designated DFN 1–6.5Since 1997 mutations have been established in 10 genes for autosomal dominant and six genes for autosomal recessive hearing loss with the result that important scientific insights into the biological basis of hearing and deafness in different clinical situations have been recorded. Moreover, …