Objective: To illustrate a family of episodic ataxia type 2 with atypical presentations and a novel mutation of CACNA1A gene

Background: The episodic ataxias (EAs) are a group of rare autosomal dominant diseases characterized by recurrent attacks of vertigo and cerebellar ataxia. EA type 2(EA2) is characterized by longer attacks of vertigo, and associated with headache and nystagmus both during and between the episodes. The CACNA1A gene is responsible for EA2 (MIM 108500). Here, we confirmed an EA2 family with a novel mutation of CACNA1A gene by whole-exome sequencing.

Methods: Neurologic examinations were conducted for the patient and his affected family members. DNA samples from the proband, one affected family member and one unaffected family member were analyzed with whole-exome sequencing and confirmed the novel mutation.

Results: A 40-year-old man complained of episodic unsteady gait, vertigo and vomiting since childhood, When vertigo developed, it accompanied with gait unsteadiness, shortness of breath, nausea, vomiting, four limbs tremor, and cold sweating. The episodes usually lasted for hours. Sleeping a while could relieve the symptoms. It occurred several times per month, and sometimes even daily. He noticed that drinking coffee must induce vertigo attack. His mother, older brother and son also had similar symptoms but milder and they did not notice any obvious precipitant. He presented with scanning speech and poor tandem gait but no nystagmus between attacks. The proband did not respond to acetazolamide treatment but temporarily underwent fewer attacks with Levetiracetam. A deletion mutation of CACNA1A gene, c.3014delG, was confirmed by Whole-Exome Sequencing.

Conclusions: This EA2 family presented atypical symptoms and carried a novel CACNA1A gene mutation. Further functional validation could help us to know the detailed mechanisms and possible treatments.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/novel-cacna1a-gene-mutation-in-a-taiwan-family-with-episodic-ataxia-type-2/