Abstracts

Rationale: Mutations in the Tre2/Bub2/Cdc16 (TBC) 1 domain family member 24 (TBC1D24) gene are associated with a range of inherited neurological disorders including drug-resistant epilepsy. Recently, advances in molecular genetic technologies have enabled accelerated gene discovery, adding to our understanding of rare genetic epilepsy and epilepsy syndrome. Herein, we report on three patients with TBC1D24 gene mutation-related focal status epilepticus. Methods: Three patients, from two families, had seizure onset at neonatal stage in two and at age of 7 months in one. All patients presented with seizure semiologies consisting of long-lasting, from minutes to hours, unilateral, focal clonic seizures of the face, tongue, arm, hand, leg or foot in addition to generalized clonic seizure or myoclonic seizure. Interictal EEG features of 3 patients showed normal results. Ictal EEG was recorded in one patient with characteristics of myoclonic seizures at sleep stage and it showed focal spikes over F4. Brain MRI of all patients revealed negative findings. Diagnostic whole genome sequencing was performed. Results: Patient 1 had compound heterozygous TBC1D24 c.1499C>T (p.Ala500Val) and c.119G>A (p.Arg40His) gene mutations from the father and the mother, respectively. Patients 2 and 3 were siblings and had homozygous TBC1D24 c.1499C>T (p.Ala500Val) gene mutations. All three patients experienced refractory focal status epilepticus despite administration of multiple antiepileptic drugs and the ketogenic diet. The two siblings exhibited seizure aggravation while febrile illnesses. All patients had mild to moderate developmental delay. Conclusions: TBC1D24-related epilepsy can manifest with developmental delays and a variety of focal-onset seizures prone to electroclinical dissociation. Early diagnosis is important to provide genetic counseling for the patients’ families. Funding: No funding