CACNA1A encodes the Cav2.1 (P/Q-type) channel whose spectrum extends from FHM1/EA2/SCA6 to epilepsy and vertigo, but penetrance-especially sex differences-remains unclear. We report a three-generation family with CACNA1A c.5610del, detail electroclinical features, assess sex-stratified penetrance, and discuss individualised therapy.
Audiologists encountering patients with unexplained episodic vertigo alongside migraine, ataxia, or family history of these conditions should consider referral for genetic evaluation of CACNA1A and related channelopathies.
This case series highlights the wide spectrum of symptoms caused by CACNA1A variants, reinforcing that episodic vertigo in the clinic may have an underlying genetic channelopathy that warrants multidisciplinary and genetic evaluation.
- 01CACNA1A c.5610del variant identified in a three-generation family with epilepsy, ataxia, migraine, and vertigo.
- 02Same gene variant causes markedly different symptoms across family members — high phenotypic variability.
- 03Study explores penetrance (how often the gene change causes symptoms) and sex-based differences.
- 04Vertigo is a recognised but underemphasised feature of CACNA1A-related disorders.
- 05Published in BMC Neurology as a case series — evidence is preliminary and hypothesis-generating.
The CACNA1A c.5610del variant causes variable expression including epilepsy, ataxia, migraine, and vertigo within the same family.
studysupportedSex differences influence the penetrance or expression of CACNA1A c.5610del-related phenotypes.
studyunclear- PMID
- 42067833
- DOI
- 10.1186/s12883-026-04944-z.
- Journal
- BMC Neurology
- Publication type
- case_report
- Evidence level
- 4
- Population
- Three-generation family carrying the CACNA1A c.5610del variant presenting with epilepsy, ataxia, migraine, and vertigo
- Intervention
- Genetic characterisation of CACNA1A c.5610del variant
Primary outcomes
Phenotypic spectrum associated with CACNA1A c.5610del; Penetrance and sex-related differences in symptom expression