ABSTRACT
Pathogenic missense variants in COCH are associated with DFNA9, an autosomal dominantly inherited type of progressive sensorineural hearing loss with or without vestibular dysfunction. This study is a comprehensive overview of genotype-phenotype correlations using the PRISMA and HuGENet guidelines. Study characteristics, risk of bias, genotyping and data on the self-reported age of onset, symptoms of vestibular dysfunction, normative test results for vestibular function, and results of audiovestibular examinations were extracted for each underlying pathogenic COCH variant. The literature search yielded 48 studies describing the audiovestibular phenotypes of 27 DFNA9-associated variants in COCH. Subsequently, meta-analysis of audiometric data was performed by constructing age-related typical audiograms and by performing non-linear regression analyses on the age of onset and progression of hearing loss. Significant differences were found between the calculated ages of onset and progression of the audiovestibular phenotypes of subjects with pathogenic variants affecting either the LCCL domain of cochlin or the vWFA2 and Ivd1 domains. We conclude that the audiovestibular phenotypes associated with DFNA9 are highly variable. Variants affecting the LCCL domain of cochlin generally lead to more progression of hearing loss when compared to variants affecting the other domains. This review serves as a reference for prospective natural history studies in anticipation of mutation-specific therapeutic interventions.
Subject(s)
Extracellular Matrix Proteins , Hearing Loss, Sensorineural , Vestibular Diseases , Extracellular Matrix Proteins/genetics , Genetic Association Studies , Hearing Loss, Sensorineural/genetics , Humans , Mutation , Prospective Studies , Vestibular Diseases/genetics , Vestibular Diseases/pathologyABSTRACT
No evidenced-based guidelines exist for the treatment of extracranial carotid artery aneurysms (ECAAs). The "gold standard" for symptomatic ECAAs is surgical intervention. In distally located ECAAs just below the base of the skull, endovascular monotherapy may be beneficial. We present the case of a 21-year-old man with a symptomatic saccular aneurysm in the distal internal carotid artery receiving a flow-diverting stent. The stent was successfully positioned without adverse procedural events. At 6 months, computed tomography angiography revealed secondary occlusion of the aneurysm without further complications. The flow-diverting stent may serve as an additional treatment option for the endovascular specialist considering invasive treatment in patients with an ECAA.