Episodic Ataxia Type 2 Presenting with Fluctuating Weakness in a Child with a De Novo CACNA1A Variant

Background: Episodic ataxia type 2 (EA2) is the most common subtype of episodic ataxia and is primarily caused by pathogenic variants in the CACNA1A gene. Although classically characterized by paroxysmal ataxia, CACNA1A-related disorders are increasingly recognized as an age-dependent phenotypic continuum that extends beyond episodic cerebellar dysfunction to include fluctuating weakness, persistent neurological signs, and neurodevelopmental impairments. Case report: A 12-year-old boy presented with episodic vertigo. His medical history was notable for infantile paroxysmal tonic upward gaze beginning at 6 months of age. From the age of 7 years, he developed frequent episodes of vertigo and ataxia lasting 2 to 3 h. At 10 years of age, he experienced an episode of acute lower limb weakness with diminished deep tendon reflexes, without prominent ataxia. Guillain–Barré syndrome was initially suspected, and he received two courses of intravenous immunoglobulin, with only transient improvement. Neurophysiological studies were largely unremarkable, except for an isolated decremental response on repetitive nerve stimulation. In addition to paroxysmal events, he exhibited persistent interictal cerebellar signs, including dysmetria, dysdiadochokinesia, and downbeat nystagmus. Neuropsychological testing revealed mild intellectual disability with prominent visuospatial deficits. Trio-based whole-exome sequencing identified a de novo CACNA1A splice donor variant (c.978 + 1G > A), confirming the diagnosis of EA2. Treatment with acetazolamide resulted in marked improvement in episodic ataxic events. Conclusions: This case highlights EA2 as part of a broader CACNA1A-related phenotypic continuum rather than a purely paroxysmal disorder. Awareness of atypical and age-dependent manifestations is crucial to avoid diagnostic pitfalls and to facilitate the timely initiation of targeted therapy and appropriate developmental support.