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A NOVEL KCNA1 MUTATION CAUSES EPISODIC ATAXIA TYPE 1 WITH PERSISTENT CEREBELLAR DEFICITS
Objectives: Episodic ataxia type 1 (EA1) is an autosomal dominant disorder associated with mutations in the potassium channel gene KCNA1. It is characterized by brief episodes of ataxia and interictal myokymia. Phenotypic variants including partial epilepsy have been reported. We further illustrate the phenotypic variability of this disorder by describing the unique clinical features present in a family found to have a novel KCNA1 mutation.
Methods: The clinical features and KCNA1 mutation identified in a mother and son with EA1 are described.
Results: The male proband presented at birth with hypertonia and persistently clenched fists. He developed partial seizures at 2 months of age. At 2 years of age lower extremity joint contractures and seizures persist. He is also globally delayed. The proband's mother presented similarly at birth. Her seizures began at 10 days of age but resolved in infancy. Persistent cerebellar dysarthria and ataxia began at 2 years of age. Brief episodes of vertigo followed. Her IQ was determined to be in the low average range. Continuous electrical activity on EMG noted in infancy was confirmed to be myokymia in adulthood. Brain MRI showed cerebellar hypoplasia. A novel point mutation at highly conserved site in KCNA1 resulting in amino acid substitution of valine to leucine at position 408 was found only in affected family members.
Conclusion: Patients with EA1 may also develop cerebellar hypoplasia and clinical cerebellar signs, which are features described for Episodic Ataxia type 2. The cognitive difficulties and global developmental delay are additional unique features in this family. This family illustrates the clinical variability and expands the phenotype of this potassium channelopathy.