Genetics of recurrent vertigo and vestibular disorders.

Irene Gazquez,Jose A Lopez-Escamez

doi:10.2174/138920211797248600

Abstract

We present recent advances in the genetics of recurrent vertigo, including familial episodic ataxias, migraneous vertigo, bilateral vestibular hypofunction and Meniere’s disease.Although several vestibular disorders are more common within families, the genetics of vestibulopathies is largely not known. Genetic loci and clinical features of familial episodic ataxias have been defined in linkage disequilibrium studies with mutations in neuronal genes KCNA1 and CACNA1A. Migrainous vertigo is a clinical disorder with a high comorbidity within families much more common in females with overlapping features with episodic ataxia and migraine. Bilateral vestibular hypofunction is a heterogeneous clinical group defined by episodes of vertigo leading to progressive loss of vestibular function which also can include migraine. Meniere’s disease is a clinical syndrome characterized by spontaneous episodes of recurrent vertigo, sensorineural hearing loss, tinnitus and aural fullness and familial Meniere’s disease in around 10-20% of cases. An international collaborative effort to define the clinical phenotype and recruiting patients with migrainous vertigo and Meniere’s disease is ongoing for genome-wide association studies.

Highlights

Genomic medicine in complex middle or inner ear diseases such as chronic otitis media, otosclerosis or age-related hearing loss is an emerging topic [1]
Patients with imbalance or recurrent vertigo are a heterogeneous group of complex disorders affecting the peripheral and central vestibular system and they represent a diagnostic challenge for the clinicians since their genetic basis is largely not known
Familiar episodic ataxias are rare cause of recurrent vertigo, but molecular genetics has identified several mutations on KCNA1 and CACNA1A genes that suggest a key role for voltage-gated channels and solute carriers in the plasma membrane of neurons in recurrent vertigo

Summary

INTRODUCTION

Genomic medicine in complex middle or inner ear diseases such as chronic otitis media, otosclerosis or age-related hearing loss is an emerging topic [1]. Patients with imbalance or recurrent vertigo are a heterogeneous group of complex disorders affecting the peripheral and central vestibular system and they represent a diagnostic challenge for the clinicians since their genetic basis is largely not known. Recent advances in familiar vestibular disorders and in familial Menière’s disease have facilitated the pathways for clinical characterization and recruitment of patients for large collaborative studies. Recurrent vertigo with vestibular hypofunction is a common symptom in clinical practice and there is a hereditary component in neurotologic disorders that is not well defined. Migraine has a strong genetic background and it is frequently observed in these patients and the genomics for migraine has started to become known [2, 3], the shared allelic variants between vertigo and migraine remain to be discovered. 1389-2029/11 $58.00+.00 migrainous vertigo, bilateral vestibular hypofunction and Ménière’s disease

FAMILIAL EPISODIC ATAXIAS

Cognitive impairment

MENIERE DISEASE

Findings

Bilateral MD