Abstracts

Rationale: TBC1D24 is a protein which has been shown to have a role in developing neurons. Mutations in this gene can have different clinical manifestations, including mild infantile-onset myoclonic epilepsy with normal intellect and neuroimaging or more severe syndrome with focal epilepsy, cognitive impairment and cerebro-cerebellar malformations to severe infantile-onset myoclonic epilepsy with encephalopathy, progressive cerebral atrophy and childhood death. Only few isolated or familial cases are reported in literature. We describe the electroclinical phenotype and epilepsy course in 5 patients with TBC1D24 mutations. Methods: We retrospectively analyzed the clinical and electro-neuro-radiological features in five patients, two siblings (one male and one female) and 3 only child (2 males and 1 female) from 4 unrelated families, with early myoclonic seizures onset and psychomotor delay diagnosed with pathogenic TBC1D24 mutations detected with Sanger sequencing. Results: Three patients presented consanguinity. Mean seizure onset was 5 months (1-7 months), characterized by segmental or generalized erratic myoclonic seizure, evolving in myoclonic status epilepticus (SE). More over one patient presented with migrating focal seizures. Seizures ad SE resulted drug resistant despite different treatments. EEG could be negative at onset, later on abnormal background with focal and/or multifocal slow and epileptiform abnormalities had been recorded. Critical EEG during myoclonic SE was available in 4 patients. Focal migrating seizures had been recorded in one patient. Two patients developed encephalopathy. Seizure burden reduce during years, leaded to months/years of seizure freedom. MRI showed cerebellar atrophy in 2 patients, 1 patient presented with severe progressive cerebral and cerebellar atrophy, 2 patients with early negative MRI. Neurological examination showed severe apoxtural hypotonus in 2 patients, ataxia gait associated to tremor and dysmthria in 2 patients, language deficit in 1. All patients presented with developmental delay or mental retardation: 2 severe, 2 moderate and 1 mild. Two patients presented with neurosensorial deafness. Mean follow-up was 6,5 years (1-20 years). One patient died at the age of 20 during sleep. Conclusions: We emphasize that mutation analysis of TBC1D24 gene should be performed in patients with intractable early onset infantile myoclonic epilepsy experiencing developmental delay and progression into cerebral-cerebellar atrophy. Funding: No funding