Objective:

Our aim is to describe the neuro-ophthalmic manifestations of CACNA1A-related disorders, highlighting their role as potential presenting signs in a series of patients with genetics-confirmed diagnoses.

Background:

CACNA1A-related disorders are a group of rare channelopathies caused by voltage-gated calcium channel gene mutations. They are associated with heterogenous neurologic presentations, including ataxia, epilepsy, and intellectual disabilities. Disorders of ocular motility may be appreciated at a young age by families and clinicians. Pediatric ophthalmologists and neuro-ophthalmologists may be the first to encounter affected patients, so awareness of this entity is crucial.

Design/Methods:

Retrospective chart review of five patients with genetically-confirmed CACNA1A mutations seen at a single institution. Data collected includes disease history, exam findings, diagnostic process, and management history.

Results:

Average age is 27 (range 6-43), age at diagnosis was 22.6 (2-40). All patients had heterozygous pathogenic mutations and diagnosed episodic ataxia 2 (EA2). Three experienced hemiplegic migraines (FHMs), and one had spinocerebellar ataxia 6 (SCA6). Presenting symptoms were non-specific, including early childhood convulsions (3/5), developmental delays (4/5), and gait ataxia (3/5). Notable neuro-ophthalmic findings include multiple manifestations of nystagmus (direction changing gaze-evoked, rebound, downbeat), slow/hypometric saccades, saccadic pursuits, and intermittent diplopia from eye misalignment (with headaches, blur, and imbalance). Two patients possibly experienced paroxysmal tonic upgaze, a characteristic but often underreported finding. Best corrected visual acuity ranged from 20/25-20/40. No abnormalities were present on fundus, optic nerve, or color vision exam. Most patients had intact visual fields, one has homonymous superior quadrantanopia after anterior medial temporal lobectomy for medication-refractory seizures. Other shared features include recurrent migraines (4/5), medication-resistant seizures (2/5), intellectual disability (2/5), and cerebellar volume loss on neuroimaging (2/5).

Conclusions: