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.
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Data availability
The data supporting the study findings are available from the corresponding author upon reasonable request.
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Funding
The authors did not receive support from any organization for the submitted work.
DR received travel grants from AbbVie. MT reports no financial disclosures. CL received a travel grant from Lusofarmaco. FDM received travel grants from AbbVie. MGR received honoraria for lecturing and travel grants from Medtronic, UCB Pharma, and AbbVie. LL received honoraria for lecturing and travel grants from Medtronic, UCB Pharma, and AbbVie. CAA received travel grants from Zambon and AbbVie and educational grants from Ralpharma.
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Authors and Affiliations
Contributions
Domiziana Rinaldi: study conception and design; interpretation of data; drafting the manuscript.
Marta Tangari: study conception and design; interpretation of data; drafting the manuscript.
Claudia Ledda: study conception and design; interpretation of data; drafting the manuscript.
Francesca Dematteis: acquisition and interpretation of data; revising the manuscript for intellectual content.
Mario Giorgio Rizzone: interpretation of data; revising the manuscript for intellectual content.
Leonardo Lopiano: interpretation of data; revising the manuscript for intellectual content.
Carlo Alberto Artusi: study conception and design; interpretation of data; revising the manuscript for intellectual content.
All the co-authors listed above gave their final approval of this manuscript version.
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Supplementary file1 Supplementary Video 1. Neurological examination of the patient in 2019 (MP4 5755 KB)
Supplementary file2 Supplementary Video 2. Neurological examination of the patient in 2021 (MP4 18003 KB)
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Rinaldi, D., Tangari, M.M., Ledda, C. et al. CACNA1A variant associated with generalized dystonia. Neurol Sci (2024). https://doi.org/10.1007/s10072-024-07592-8
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DOI: https://doi.org/10.1007/s10072-024-07592-8