Understanding Otosclerosis Etiology and Impacting Factors

What is the current understanding of the etiology of otosclerosis and what are the genetic and environmental factors that have been implicated in the disease?

Background: A common disease characterized by a disordered bone remodeling in the otic capsule, otosclerosis has a prevalence of about 0.3 percent to 0.4 percent in the Caucasian population. In 10 percent of cases, a sensorineural hearing loss is present in addition to the conductive hearing loss. Although many environmental and genetic factors have been suggested for the development of otosclerosis, a great part of the etiology remains a mystery.

Study Design: A contemporary review

Setting: Department of Medical Genetics, University of Antwerp, Antwerp, Belgium

Synopsis: The data suggest that measles virus infection is probably a susceptibility factor involved in otosclerosis but not the single cause or necessary for the disease to manifest. Endocrine factors could be involved because of the large difference in prevalence between males and females (1:2). In addition, epidemiological studies show otosclerosis associated with low fluoride content in the drinking water. Evidence for genetic variants in otosclerosis has been discovered in different parts of the spectrum, but the extent to which these contribute to the disease is unclear since only a limited number of genetic studies have been done. Most cases of otosclerosis, however, do not have a clear familial background. The success in identifying loci in large otosclerosis families by linkage analysis has been hampered by the presence of reduced penetrance and phenocopies. The authors noted that recently they have been able to provide strong evidence for T cell receptor beta as the responsible gene at the OTSC2 region. The authors also discussed association studies for otosclerosis, including genes in the immune system, in bone remodeling and in hormonal and other pathways. Regarding otosclerosis as an autoimmune disease, the authors said the precise underlying mechanism might vary among otosclerosis patients as several factors can influence and contribute to a similar disease outcome and it is unclear whether an autoimmune pathology underlies disease development.

Bottom Line: Overall, studies suggest a heterogeneous etiology for otosclerosis with the extent of involvement of environmental versus genetic factors unclear.

Citation: Schrauwen I, Van Camp, G. The etiology of otosclerosis: a combination of genes and environment. Laryngoscope. 2010; 120(6):1195-1202.

—Reviewed by Sue Pondrom