| Locus (OMIM) | Gene (OMIM) | Inheritance | Key Locus References (PubMed) | Key Gene References (PubMed) | Evidence (ClinGen)  |
|---|---|---|---|---|---|
| OTSC1 | unknown | Autosomal Dominant | Tomek et al., 1998 | n/a | n/a |
| OTSC2 | unknown | Autosomal Dominant | Van Den Bogaert et al., 2001 | n/a | n/a |
| OTSC3 | unknown | Autosomal Dominant | Chen et al., 2002 | n/a | n/a |
| OTSC4 | unknown | Autosomal Dominant | Brownstein et al., 2006 | n/a | n/a |
| OTSC5 | unknown | Autosomal Dominant | Van Den Bogaert et al., 2004 | n/a | n/a |
| OTSC7 | unknown | Autosomal Dominant | Thys et al., 2007 | n/a | n/a |
| OTSC8 | unknown | Autosomal Dominant | Bel Hadj Ali et al., 2008 | n/a | n/a |
| OTSC10 | unknown | Autosomal Dominant | Schrauwen et al., 2011 | n/a | n/a |
| OTSC11 | FOXL1 | Autosomal Dominant | Abdelfatah et al., 2022 | Abdelfatah et al., 2022 | not reviewed |
| OTSC12 | SMARCA4 | Autosomal Dominant | Drabkin et al., 2024 | Drabkin et al., 2024 | not reviewed |
| unassigned | SERPINF1 (see note 1) | Autosomal Dominant | Ziff et al., 2016; Valgaeren et al., 2019 | Ziff et al., 2016; Valgaeren et al., 2019 | not reviewed |
| unassigned | MEPE | Autosomal Dominant | Schrauwen et al., 2019 | Schrauwen et al., 2019 | not reviewed |
n/a = not applicable
Note 1: Valgaeren et al., 2019 disputes the role of SERPINF1 in the pathogenesis of otosclerosis.
Clinical otosclerosis has a reported prevalence of 0.2 - 1% among white adults, making it the single most common cause of hearing impairment in this population. Mean age-of-onset is in the third decade, and 90% of affected persons are under 50 years of age at the time of diagnosis. It is characterized by isolated sclerosis of endochondral bone of the inner ear. Conductive hearing loss develops when otosclerotic foci invade the stapedio-vestibular joint (oval window) and interfere with free motion of the stapes. Sensorineural hearing loss may also be present. Although the sensorineural loss cannot be corrected, stapes microsurgery has proven to be a successful means to restore normal ossicular conduction and can improve hearing thresholds. Families with autosomal dominantly inherited otosclerosis have been described, but in most patients the etiology of the disease is unknown.