Complex epilepsy phenotype associated with chromosome 2q24.2-q24.3 deletion involving sodium channel gene cluster

Abstract

Objective

The 2q24.2-24.3 chromosome region encodes sodium channel genes important in severe childhood epilepsy, notably SCN1A linked to Dravet syndrome (DS). However, the roles of other genes, either within the SCN cluster or in the segments proximal to it, have not been clearly delineated. The combination of ketogenic diet and fenfluramine is known to provide substantial benefits to patients with DS, but there is a paucity of literature regarding its role in other developmental and epileptic encephalopathies (DEE). This report aims to further explore clinical findings and treatment outcomes in a patient with a complex epilepsy phenotype.

Methods

Our patient's extensive diagnostic evaluation revealed 14 deleted genes within the 2q24.2-24.3 chromosome region.

Results

The patient initially presented with clusters of focal motor seizures with apnea and cyanosis requiring intubation as well as prolonged hospitalizations for status epilepticus. He has baseline hypotonia, dysphagia, and developmental delay. He had a >50% reduction in his seizures following a combination of ketogenic diet and fenfluramine. His seizures are now responsive to rescue midazolam, and he no longer has status epilepticus.

Interpretation

Our patient's remarkable clinical improvement suggests that this dual therapy may be beneficial in patients with DEE exhibiting pathogenic variations in this region of chromosome 2, beyond just DS.