An episodic ataxia type 2 (EA2) kindred with ataxic spells induced by fever or high environmental temperature and a novel CACNA1A mutation were identified and reported from the Universities of Mississippi and Minnesota. The proband was a 75-year-old woman with episodes beginning in childhood of ataxia, vertigo, weakness, and migraine lasting several hours, and provoked by fever, heat, stress, or sudden movements. The proband’s father and sister were similarly affected. In 11 patients with episodic ataxia, age of onset varied from infancy to the twenties. Episodes ranged from daily to 2 annually, and lasted minutes to days. They were sometimes accompanied by headaches, diplopia, nausea, and vertigo. Those with the mutation had interictal cerebellar deficits. Early cerebellar dysfunction in EA2 results from the mutations in the neuronal calcium-channel gene and not a degenerative process. [1]

COMMENT. Episodic ataxia type 2 (EA2) is a dominantly inherited disorder, characterized by spells of ataxia, dysarthria, vertigo, and migraine, associated with mutations in the neuronal calcium-channel gene CACNA1A. Attacks are precipitated by stress, exercise, or alcohol. Some patients have nystagmus between spells and some develop a progressive ataxia in adulthood. Twenty one CACNA1A mutations have been described in EA2. The above kindred study adds a further mutation and clinical syndrome in which ataxic spells are precipitated by fever or overheating, and patients develop signs of cerebellar dysfunction between attacks. Other neurologic disorders caused by mutations in the CACNA1A gene are the dominantly inherited progressive spinocerebellar ataxia (SCA6), and familial hemiplegic migraine.