Otosclerosis is a major cause of acquired
hearing loss in adult life affecting exclusively the human temporal bone. Until recently, the etiopathogenesis of
otosclerosis was still a matter of debate. Genetic research, however, has evolved enormously the last years and unveiled important clues regarding the cause of
otosclerosis. The objective of this article is to review the genetics of
otosclerosis with special attention for the links to the bone homeostasis of the otic
capsule.
DATA SOURCES: A detailed literature study was performed focusing on the recent genetic findings in
otosclerosis and the special bone turnover of the otic
capsule. A PubMed search and own research data were used to bring the relevant information for this review together.
CONCLUSION: Unlike all other bones in the human skeleton, the otic
capsule undergoes very little remodeling after development, possibly due to local inner ear factors.
Otosclerosis is a process of pathologic increased bone turnover in the otic
capsule, which in most cases leads to stapes fixation, resulting in a
conductive hearing loss. Although environmental factors such as
estrogens,
fluoride, and
viral infection have been implicated, it is clear that genetic factors play a significant role in the manifestation of
otosclerosis. From a genetic viewpoint,
otosclerosis is considered to be a complex disease with rare autosomal dominant forms caused by a single gene. Already, 7 monogenic loci have been published, but none of the genes involved have been identified. For the complex form of
otosclerosis, caused by an interaction between genetic and environmental factors, the first susceptibility genes were identified by case-control association studies. All 3 replicated genes, TGFB1, BMP2, and BMP4, are a part of the
transforming growth factor-beta1 pathway. Data from both genetic association studies and gene expression analysis of otosclerotic bone showed that the
TGF-beta1 pathway is most likely an important factor in the pathogenesis of
otosclerosis.