Objective: Identification and characterization of a novel pedigree with ATP1A3 mutations presenting with CAPOS syndrome and hemiplegic migraine.
Methods: We have carried out clinical examinations of a three-generation pedigree with CAPOS syndrome and analyzed the ATP1A3 gene to identify causative mutations. The pedigree is of Slavic origin from Southeastern Europe.
Results: The clinical phenotype comprised cerebellar ataxia, areflexia, optic atrophy, and sensorineural hearing loss. Pes cavus was present in two of the four patients studied. The symptoms were triggered by fever and varied in severity in family members, exhibiting a chronic progressive course with or without relapses/remissions. The ATP1A3 c.2452G>A mutation was identified in the affected members of the family, while one of the mutation carriers exhibited both CAPOS and hemiplegic migraine.
Conclusions: This study confirms that the specific c.2452G>A mutation in the ATP1A3 gene is associated with the CAPOS syndrome in pedigrees of different ethnic backgrounds. In patients with febrile episodes of ataxic encephalopathy or weakness, or both, genetic analysis of the ATP1A3 gene should be warranted. This is also the first report showing the co-occurrence of hemiplegic migraine and CAPOS syndrome in a patient with ATP1A3 mutations. Migraine has not been previously documented in ATP1A3 mutation carriers.
Keywords: ATP1A3 gene; Ataxia; Cerebellum; Channelopathies; Episodic encephalopathy; Fever; Migraine.
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