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Epilepsy and episodic ataxia type 2: family study and review of the literature

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Abstract

Episodic ataxia type 2 (EA2) is a hereditary disorder characterized by paroxysmal attacks of ataxia, vertigo and nausea, due to mutations in the CACNA1A gene, which encodes for α1 subunit of the P/Q-type voltage-gated Ca2+ channel (CaV2.1). Other manifestations may be associated to CACNA1A mutations, such as migraine and epilepsy. The correlation between episodic ataxia and epilepsy is often underestimated and misdiagnosed. Clinical presentation of EA2 varies among patients and within the same family, and the same genetic mutation can lead to different clinical phenotypes. We herewith describe an Italian family presenting with typical EA2 and, in two of the family members (patients II.3 and III.1), epileptic seizures. The sequencing revealed a heterozygous deletion of 6 nucleotides in exon 28 of CACNA1A gene, present in all affected patients. Evidence suggests that mutations of CACNA1A, conferring a loss/reduction of CaV2.1 function, lead to an increase of thalamocortical excitation that contributes to epileptiform discharges. Our description highlights intra-family variability of EA2 phenotype and suggests that mutations in the CACNA1A gene should be suspected in individuals with focal or generalized epilepsy, associated with a family history of episodic ataxia.

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Acknowledgements

Data access, responsibility, and analysis: all the authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. We would like to thank the family for participating in this study.

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Authors and Affiliations

  1. Neurology Unit, Department of Neurosciences, Santa Maria della Misericordia University Hospital, ASUFC, Piazzale Santa Maria della Misericordia 15, 33100, Udine, Italy

    Lorenzo Verriello & Giada Pauletto

  2. Department of Medicine (DAME), University of Udine, Udine, Italy

    Incoronata Lonigro, Mariarosaria Valente & Francesco Curcio

  3. Clinical Neurology Unit, Department of Neurosciences, Santa Maria della Misericordia University Hospital, ASUFC, Udine, Italy

    Annacarmen Nilo, Mariarosaria Valente & Gian Luigi Gigli

  4. Department of Mathematics, Informatics and Physics (DMIF), University of Udine, Udine, Italy

    Gian Luigi Gigli

  5. Department of Laboratory Medicine, Santa Maria della Misericordia University Hospital, ASUFC, Udine, Italy

    Incoronata Lonigro, Elena Betto & Francesco Curcio

Authors
  1. Lorenzo Verriello
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  2. Giada Pauletto
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  3. Annacarmen Nilo
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  4. Incoronata Lonigro
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  5. Elena Betto
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  6. Mariarosaria Valente
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  7. Francesco Curcio
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  8. Gian Luigi Gigli
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Contributions

LV: design and conceptualized study; acquisition of data; interpreted the data; drafted and revised the manuscript for intellectual content; study supervision. GP: design and conceptualized study; acquisition of data; interpreted the data; drafted and revised the manuscript for intellectual content; study supervision. AN: acquisition of data; interpreted the data; drafted and revised the manuscript for intellectual content. IL: acquisition of data; interpreted the data; drafted and revised the manuscript for intellectual content. EB: acquisition of data; interpreted the data; revised the manuscript for intellectual content. MV, FC and GLG: revised the manuscript for intellectual content; study supervision. All the authors approved the submitted version.

Corresponding author

Correspondence to Lorenzo Verriello.

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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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The study was performed in accordance with the Declaration of Helsinki.

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Verriello, L., Pauletto, G., Nilo, A. et al. Epilepsy and episodic ataxia type 2: family study and review of the literature. J Neurol 268, 4296–4302 (2021). https://doi.org/10.1007/s00415-021-10555-0

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  • DOI: https://doi.org/10.1007/s00415-021-10555-0

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