Background: To investigate the genetic and environmental factors responsible for phenotype variability in a familycarrying a novel CACNA1A missense mutation. Mutations in the CACNA1A gene were identified as responsible for atleast three autosomal dominant disorders: FHM1 (Familial Hemiplegic Migraine), EA2 (Episodic Ataxia type 2), andSCA6 (Spinocerebellar Ataxia type 6). Overlapping clinical features within individuals of some families sharing thesame CACNA1A mutation are not infrequent. Conversely, reports with distinct phenotypes within the same familyassociated with a common CACNA1A mutation are very rare.Case presentation: A clinical, molecular, neuroradiological, neuropsychological, and neurophysiological study wascarried 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 clinicalpresentation characterized by developmental delay, poor motor coordination, hemiplegic migraine attacks,behavioral dysregulation, and EEG abnormalities. The mother showed typical episodic ataxia attacks during infancywith 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 thatother unknown modifying genes and/or environmental factors may cooperate to generate the wide intrafamilialvariability.
|Numero di pagine||7|
|Stato di pubblicazione||Published - 2020|
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