Abstracts

Rationale:
α-Dystroglycanopathies (α-DGP) are a clinically and genetically heterogeneous group of muscular dystrophies associated with defective glycosylation of α-dystroglycan. The mechanisms of epilepogenesis in α-DGP are associated with congenital brain malformations and postnatal development of an epileptogenic neuronal circuit. Seizures in α-DGP are mostly reported in Fukuyama congenital muscular dystrophy patients with FKTN mutations in Japan, and there are sparse reports in patients with other phenotype and genotype. So, we aimed to demonstrate the seizure phenotypes and electroencephalography (EEG) characteristics of α-DGP in Korean pediatric patients and correlate them with the radiologic and genotypic features.

Methods:
A total 14 patients with seizure were recruited from 42 α-DGP cohort in Seoul National University Children’s Hospital. Detailed clinical information, including seizure onset age and type, treatment response, EEG findings, radiologic and genetic tests were analyzed.

Results:
Fourteen patients (33.3%, 14/42) had seizures. During the follow-up, seven patients (16.7%) had fever provoked seizures (FS) and 10 (23.8%) had epileptic seizures (ES). The mean ages at onset of first FS and US, respectively, were 2.6 years and 5.4 years. Most seizure type of FS was generalized tonic-clonic seizure (GTCS) in six patients (85.7%, 6/7). Among the ten patients (23.8%, 10/42) with ES, five patients had focal seizures and seven had generalized seizures. Most patients (13/14, 92.9%) were treated with antiseizure medication (ASM) due to repeated FS or epilepsy and almost half of patients (6/13, 46.2%) showed poor response to ASM. Of the 14 patients, 11 patients (78.6%) had abnormal EEG results, including interictal epileptiform discharges (IEDs) in eight patients, both IEDs and abnormal background activities (BGA) in two patients, and abnormal BGA in one patient. Except one patient with only several episodes of prolonged FS, most patients showed severe radiologic finding with cortical malformation and white matter changes. Pathogenic variants were identified in 12 patients (12/14, 85.7%), 9 with FKTN, two with GMPPB, and one with POMGNT1 variant. Overall seizure phenotype and EEG findings showed no significant differences according to genotype. The brain magnetic resonance imaging (MRI) of 13 patients (13/14, 92.9%) showed various abnormalities including neuronal migration disorder. Three patients without ES showed polymicrogria limited in frontal or froto-temporal region. However, ten patients with ES showed more diffuse polymicrogyria from frontal to temporo-parietal region.

Conclusions:
The seizure phenotype of α-DGP can be presented with various features, not only by GTCS with fever. Seizure control were relatively poor than previous reported. More diffuse cortical malformations in brain MRI may suggest evolution to ES. A careful monitoring of seizures should be considered to manage α-DGP.

Funding: No funding.