Variable clinical features in patients with CDH23 mutations (USH1D-DFNB12)
Ronald J E Pennings1, Vedat Topsakal, Lisa Astuto
1Department of Otorhinolaryngology, UMC St Radboud, Nijmegen, The Netherlands. r.pennings@kno.umcn.nl
Summary
Mutations in the CDH23 gene cause hearing loss. Missense mutations result in a milder form (DFNB12) with normal vision and vestibular function, while splice-site mutations cause Usher syndrome Type 1D (USH1D).
Area of Science:
- Genetics
- Ophthalmology
- Audiology
Background:
- The CDH23 gene is implicated in hereditary hearing loss and vision disorders.
- Mutations in CDH23 are associated with both non-syndromic hearing loss (DFNB12) and Usher syndrome Type 1D (USH1D).
Purpose of the Study:
- To characterize the audiovestibular and ophthalmologic findings in families with CDH23 gene mutations.
- To differentiate the clinical phenotypes associated with different types of CDH23 mutations.
Main Methods:
- A family study involving four DFNB12 and six USH1D patients with confirmed CDH23 mutations.
- Comprehensive audiovestibular assessments including pure-tone audiometry and vestibular reflex testing.
- Detailed ophthalmologic examinations covering visual acuity, retinal function, and ocular imaging.
Main Results:
- USH1D patients exhibited significantly greater hearing impairment compared to DFNB12 patients.
- DFNB12 patients, with missense CDH23 mutations, presented with normal retinal and vestibular function.
- USH1D patients, with splice-site CDH23 mutations, displayed a typical Usher syndrome Type I phenotype; one DFNB12 patient showed subtle yellowish retinal flecks.
Conclusions:
- Recessive missense CDH23 mutations lead to a milder DFNB12 phenotype than splice-site mutations causing USH1D.
- DFNB12 patients may present with bilateral flecks, potentially indicating lipofuscin accumulation, despite normal retinal function.
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