Abstract
The Thr226Met pathologic variant of the SCN1A gene has been associated with the clinical development of an early infantile developmental
and epileptic encephalopathy (EIDEE) different from Dravet's syndrome. The electrophysiological
mechanisms of the mutated channel lead to a paradoxical gain and loss of function.
The use of sodium channel blockers (SCB) that counteract this gain of function has
been described in previous studies and they can be safely administered to patients
carrying mutations in other sodium channel subtypes without causing a worsening of
seizures. We report the use of SCB in a child harboring the Thr226Met pathologic variant
of SCN1A with early-onset pharmaco-resistant migrating seizures, as well as developmental
delay. Lacosamide led to a dramatic reduction in seizure frequency; however, only
a mild improvement in the epileptic activity depicted by electroencephalography (EEG)
was achieved. The introduction of carbamazepine as an add-on therapy led to a notable
reduction in epileptic activity via EEG and to an improvement in sensorimotor development.
Despite the overall clinical improvement, the patient developed febrile seizures and
a nonepileptic jerking of the right hand. In this case of EIDEE with the Thr226Met
variant, we demonstrate a beneficial pharmacological intervention of SCB in contrast
to findings described in current literature. Our report encourages the cautious use
of SCB at early stages of the disease in patients carrying this pathologic variant.
Keywords
SCN1A
- Thr226Met - early infantile developmental and epileptic encephalopathy - sodium
channel blocker - gain and loss of function - voltage gated sodium channel
