A review on the genetics of otosclerosis

The aetiology of otosclerosis is not fully understood despite intensive research. It is, however, certain that a genetic component plays a significant role in the manifestation of otosclerosis, although the precise mode of inheritance is still uncertain.

To provide an up-to-date review for the genetics of otosclerosis. The mode of inheritance, chromosomal and linkage studies are presented. In addition, the possible genetic relationship between otosclerosis and osteogenesis imperfecta, and the association between otosclerosis and specific human leucocyte antigen types are described.

Systematic analysis of the literature was focused on any information related to the genetics of otosclerosis.

A MEDLINE search (1960-2007) was undertaken to perform a comprehensive review. Articles were also identified through searches of the files of authors.

The majority of epidemiological studies on families with otosclerosis suggest an autosomal dominant mode of inheritance with reduced penetrance of approximately 40%. Genetic linkage studies have demonstrated the presence of six loci (OTSC1, OTSC2, OTSC3, OTSC4, OTSC5 and OTSC7) located on chromosomes 15q, 7q, 6p, 16q, 3q and 6q respectively. Although these loci have been mapped, no causative genes have been identified, and we have little idea of the molecular process involved in this disease. While clinical similarities and some unreplicated genetic association studies suggest an aetiological relationship between otosclerosis and osteogenesis imperfecta-type I, there is no definite evidence of a common pathological process between the two diseases.

Otosclerosis may be considered as a complex disease with relatively common monogenic forms. Knowledge of these genes could lead to substantial improvements in our ability to diagnose and possibly even prevent or treat this type of hearing deterioration.