Abstract
In the last decade, variants in the Ca2+ channel gene CACNA1A emerged as a frequent aetiology of rare neurological phenotypes sharing a common denominator of variable paroxysmal manifestations and chronic cerebellar dysfunction. The spectrum of paroxysmal manifestations encompasses migraine with hemiplegic aura, episodic ataxia, epilepsy and paroxysmal non-epileptic movement disorders. Additional chronic neurological symptoms range from severe developmental phenotypes in early-onset cases to neurobehavioural disorders and chronic cerebellar ataxia in older children and adults.
In the present review we systematically approach the clinical manifestations of CACNA1A variants, delineate genotype–phenotype correlations and elaborate on the emerging concept of an age-dependent phenotypic spectrum in CACNA1A disease. We furthermore reflect on different therapy options available for paroxysmal symptoms in CACNA1A and address open issues to prioritize in the future clinical research.
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Indelicato, E., Boesch, S. (2023). CACNA1A-Related Channelopathies: Clinical Manifestations and Treatment Options. In: Striessnig, J. (eds) Voltage-gated Ca2+ Channels: Pharmacology, Modulation and their Role in Human Disease. Handbook of Experimental Pharmacology, vol 279. Springer, Cham. https://doi.org/10.1007/164_2022_625
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