Two distinct phenotypes, hemiplegic migraine and episodic Ataxia type 2, caused by a novel common CACNA1A variant

Rosaria Nardello, Giorgia Plicato, Giuseppe Donato Mangano, Elena Gennaro, Salvatore Mangano, Filippo Brighina, Vincenzo Raieli, Antonina Fontana

Research output: Contribution to journalArticlepeer-review


BACKGROUND: To investigate the genetic and environmental factors responsible for phenotype variability in a family carrying a novel CACNA1A missense mutation. Mutations in the CACNA1A gene were identified as responsible for at least three autosomal dominant disorders: FHM1 (Familial Hemiplegic Migraine), EA2 (Episodic Ataxia type 2), and SCA6 (Spinocerebellar Ataxia type 6). Overlapping clinical features within individuals of some families sharing the same CACNA1A mutation are not infrequent. Conversely, reports with distinct phenotypes within the same family associated with a common CACNA1A mutation are very rare.

CASE PRESENTATION: A clinical, molecular, neuroradiological, neuropsychological, and neurophysiological study was carried out in proband and his carrier mother. The new heterozygous missense variant c.4262G > A (p.Arg1421Gln) in the CACNA1A gene was detected in the two affected family members. The proband showed a complex clinical presentation characterized by developmental delay, poor motor coordination, hemiplegic migraine attacks, behavioral dysregulation, and EEG abnormalities. The mother showed typical episodic ataxia attacks during infancy with no other comorbidities and mild cerebellar signs at present neurological evaluation.

CONCLUSIONS: The proband and his mother exhibit two distinct clinical phenotypes. It can be hypothesized that other unknown modifying genes and/or environmental factors may cooperate to generate the wide intrafamilial variability.

Original languageEnglish
Pages (from-to)155
JournalBMC Neurology
Issue number1
Publication statusPublished - Apr 26 2020


  • Ataxia/genetics
  • Calcium Channels/genetics
  • Child
  • Family
  • Humans
  • Male
  • Migraine with Aura/genetics
  • Mutation, Missense
  • Nystagmus, Pathologic/genetics
  • Phenotype


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