Objective:

NA

Background:

Pathogenic variants in SCN1A are classically linked to epileptic encephalopathies such as Dravet syndrome and GEFS+, but have also been associated with familial hemiplegic migraine type 3 (FHM3). Recent studies indicate that certain SCN1A variants may produce mixed phenotypes, blurring clinical boundaries between epilepsy, migraine, and episodic encephalopathy, thereby complicating diagnostic and therapeutic decisions.

Design/Methods:

NA

Results:

A 13-year-old right-handed male with a history of language delay, ADHD, and depression presented with recurrent episodes of altered awareness and abnormal behavior beginning at age 8. Episodes were triggered by exertion or illness and featured a prodrome of headache and dizziness, followed by pallor, unresponsiveness, glazed expression, toe-walking, nausea, and dream-like awareness. Events lasted 5–40 minutes, with prolonged postictal confusion. EEG showed rare generalized spike-wave discharges during sleep. Brain MRI and metabolic studies were unremarkable. Genetic testing identified a heterozygous pathogenic SCN1A variant (c.5620C>T; p.Arg1874Trp), inherited from an asymptomatic father. Symptoms resolved with Levetiracetam (750 mg BID), with no recurrence over 3 years. The absence of febrile seizures, hemiplegia, and developmental regression argued against classic epileptic encephalopathy. Given the episodic nature and associated symptoms, FHM3 remains a diagnostic consideration.

Conclusions:

This case illustrates the expanding phenotypic spectrum of SCN1A-related disorders and raises the possibility that FHM3 may present in childhood with atypical features mimicking epilepsy or encephalopathy. Functional studies and long-term phenotyping of individuals with SCN1A variants are needed to clarify genotype–phenotype correlations. Clinicians should consider FHM3 in exertion- or illness-induced episodic encephalopathy, particularly when associated with preserved cognition and a positive family history.