Episodic Vestibulocerebellar Ataxia Associated with a CACNA1G Missense Variant

Gazulla J. ; Izquierdo-Alvarez S. ; Ruiz-Fernández E. ; Lázaro-Romero A. (Universidad de Zaragoza) ; Berciano J.

Resumen: Episodic vestibulocerebellar ataxias are rare diseases, frequently linked to mutations in different ion channels. Our objective in this work was to describe a kindred with episodic vestibular dysfunction and ataxia, associated with a novel CACNA1G variant. Two individuals from successive generations developed episodes of transient dizziness, gait unsteadiness, a sensation of fall triggered by head movements, headache, and cheek numbness. These were suppressed by carbamazepine (CBZ) administration in the proband, although acetazolamide and topiramate worsened instability, and amitriptyline and flunarizine did not prevent headache spells. On examination, the horizontal head impulse test (HIT) yielded saccadic responses bilaterally and was accompanied by cerebellar signs. Two additional family members were asymptomatic, with normal neurological examinations. Reduced vestibulo-ocular reflex gain values, overt and covert saccades were shown by video-assisted HIT in affected subjects. Hearing acuity was normal. Whole-exome sequencing demonstrated the heterozygous CACNA1G missense variant c.6958G>T (p.Gly2320Cys) in symptomatic individuals. It was absent in 1 unaffected member (not tested in the other asymptomatic individual) and should be considered likely pathogenic. CACNA1G encodes for the pore-forming, a1G subunit of the T-type voltage-gated calcium channel (VGCC), in which currents are transient owing to fast inactivation, and tiny, due to small conductance. Mutations in CACNA1G cause generalized absence epilepsy and adult-onset, dominantly inherited, spinocerebellar ataxia type 42. In this kindred, the aforementioned CACNA1G variant segregated with disease, which was consistent with episodic vestibulocerebellar ataxia. CBZ proved successful in bout prevention and provided symptomatic benefit in the proband, probably as a result of interaction of this drug with VGCC. Further studies are needed to fully determine the vestibular and neurological manifestations of this form of episodic vestibulocerebellar ataxia. This novel disease variant could be designated episodic vestibulocerebellar ataxia type 10. © 2021 The Author(s). Published by S. Karger AG, Basel.

Idioma: Inglés

DOI: 10.1159/000515974

Año: 2021

Publicado en: Case reports in neurology 13, 2 (2021), 347-354
ISSN: 1662-680X

Factor impacto CITESCORE: 0.9 - Medicine (Q3)

Factor impacto SCIMAGO: 0.263 - Neurology (clinical) (Q3)

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Area Medicina (Dpto. Medicina, Psiqu. y Derm.)