CACNA1A variant associated with generalized dystonia. in Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology / Neurol Sci. 2024 Sep;45(9):4589-4592. doi: 10.1007/s10072-024-07592-8. Epub 2024 May 14.

2024
AOU Città della Salute di Torino
ASL Torino 3

Tipo pubblicazione

Journal Article

Autori/Collaboratori (7)Vedi tutti...

Artusi CA
Department of Neuroscience "Rita Levi Montalcini", University of Torino, Turin, Italy.
Rizzone MG
Neurology 2 Unit, A.O.U. Città Della Salute E Della Scienza Di Torino, Corso Bramante 88, 10126, Turin, Italy.
Lopiano L
Department of Neurology, Ospedale Di Rivoli, ASL TO 3, Via Rivalta 29, 10098, Rivoli, Turin, Italy.

et alii...

Abstract

INTRODUCTION: CACNA1A gene variants are correlated with different disorders, including episodic ataxia type 2, spinocerebellar ataxia type 6, and familial hemiplegic migraine type 1. Despite dystonia not being a typical manifestation of CACNA1A variants, there are reports indicating a link between this gene mutation and dystonic features. METHODS: We report the case of a patient with a novel missense variant of the CACNA1A gene presenting headache, head and arm tremor, dystonia, episodic painful focal dystonic attacks, and unexplained falls. RESULTS:  A 57-year-old woman presented with a history of neck dystonia, head and arm tremor, and headaches since age 15. In 2017, she progressively developed dystonic tremor of the head and arms with an unremarkable brain MRI. In 2018 she experienced worsening of tremor and developed painful dystonic attacks, resistant to treatments including clonazepam, trihexyphenidyl, baclofen, and levodopa/benserazide. Botulinum toxin injections for neck dystonia provided limited benefit. The next-generation sequencing exam revealed a CACNA1A gene missense variant (NM_023035.2:c.1630C?>?T; p.Arg544Trp). In 2021 we observed a worsening of dystonia, accompanied by weight loss, mood changes, and unexplained falls. Deep brain stimulation was considered but ruled out due to cortical atrophy and mild cognitive deficits revealed by the neuropsychological examination. DISCUSSION: Only a few studies reported dystonia as part of the clinical features in carriers of CACNA1A mutations. This case points out the relevance of a need to expand the literature on voltage-dependent P/Q-type Ca2?+?channels' role in dystonia's pathogenesis and stresses the complex phenotype-genotype presentation of CACNA1A mutation.

Accesso banca dati bibliografica

PMID : 38743163

DOI : 10.1007/s10072-024-07592-8

Keywords

Tremor; Headache; Dystonia; Cerebellum; Dystonia/genetics; CACNA1A; Dystonic Disorders/genetics; Calcium Channels/genetics; Mutation, Missense; Middle Aged; Female; Humans;