Sibling cases of DEPDC5-related developmental and epileptic encephalopathy successfully treated with lacosamide

Abstract

Background

DEPDC5 is a causative gene for various familial focal epilepsies. We report the cases of two Japanese sisters with DEPDC5-related epilepsy presenting as developmental and epileptic encephalopathy (DEE) that were successfully treated with lacosamide as add-on therapy.

Patients

The elder sister had focal tonic seizures at 3 years 10 months old. Long-term video-electroencephalography (EEG) monitoring disclosed that she also had atypical absence seizures with asymmetric generalized slow spike-and-wave complexes, leading to a diagnosis of Lennox-Gastaut syndrome (LGS). Zonisamide, levetiracetam, and sodium valproate (VPA) failed to resolve her seizures, but subsequent lacosamide (LCM) treatment effectively stopped them. At 4 years and 6 months of age, her development was normal. Her younger sister had experienced epileptic spasms at 4 months of age. Her interictal EEG showed hypsarrhythmia, leading to a diagnosis of infantile epileptic spasms syndrome (IESS). VPA was partially effective at decreasing her epileptic spasms, and an add-on therapy of LCM finally suppressed her seizures with normalization of her EEG. At 1 year and 2 months of age, she had developed normally without seizures. The two sisters' brain MRI findings eventually became unremarkable. Trio-based whole-exome sequencing identified a heterozygous germline variant in the DEPDC5 gene (NM_001242896: exon37: c.3751delT: p.F1251fs) in both sisters and their asymptomatic mother, illustrating the variant's incomplete penetrance.

Conclusion

The DEPDC5 variant can be causative for LGS and IESS with no malformations of cortical development. LCM may be effective for drug-resistant DEPDC5-related DEE.