Adult-Onset Neurological Deterioration in Dravet Syndrome Associated With a Novel SCN1A Missense Variant (p.Gly1371Asp): A Case Report

TL;DR

A 26-year-old woman with Dravet syndrome experienced new neurological symptoms in adulthood linked to a novel SCN1A gene variant.

Contribution

Reports a novel SCN1A missense variant (p.Gly1371Asp) associated with adult-onset neurological deterioration in Dravet syndrome.

Findings

The patient developed progressive tremor, postural instability, and dysphagia beginning at age 20.

Neuroimaging showed new basal ganglia and thalamic calcifications not present in childhood.

A de novo SCN1A missense variant (p.Gly1371Asp) was identified as the genetic cause.

Abstract

We report the case of a 26-year-old woman with genetically confirmed Dravet syndrome (DS) who experienced atypical neurological deterioration in early adulthood, despite a previously stable clinical course. Her early history met the classical DS criteria, with the onset of febrile and afebrile seizures in infancy, followed by myoclonic, focal, and absence seizures, as well as developmental delay. Beginning at age 20, however, she developed new symptoms, including progressive tremor, postural instability, frequent gelastic-like seizures, and dysphagia severe enough to require temporary nasogastric feeding. Neuroimaging revealed basal ganglia and thalamic calcifications that had not been present in childhood. Mitochondrial evaluation demonstrated a mild reduction in oxygen consumption, despite normal enzyme activity. Genetic analysis, performed for the first time in adulthood, identified a previously unreported de novo missense variant in SCN1A (c.4112G>A, p.Gly1371Asp). This case highlights the potential for adult-onset phenotypic progression in SCN1A-related epilepsy and may broaden the clinical spectrum of DS, underscoring the importance of ongoing surveillance during adulthood, particularly in patients with rare or novel SCN1A missense variant (p.Gly1371Asp).

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