VP.78 Clinical and genetic study of LAMA2-related muscular dystrophy patients with seizures

Abstract

<i>LAMA2</i>-related muscular dystrophy (LAMA2-MD) is an autosomal recessive muscular dystrophy caused by pathogenic variants in <i>LAMA2</i> gene, including two subgroups: severe, early-onset <i>LAMA2</i>-related congenital muscular dystrophy (LAMA2-CMD) and mild, late-onset autosomal recessive limb-girdle muscular dystrophy-23 (LGMD R23). Seizures frequently occurred in LAMA2-MD, however, the relationship between seizures and genotype in LAMA2-MD is not fully known. The clinical information of seizures including seizure type, frequency, treament, EEG changes, brain MRI and genetic data of LAMA2-MD patients from Peking University First Hospital between January 2003 and March 2022 were collected and analyzed. Among 141 LAMA2-MD patients, seizures were observed in 10.5% (13/124) of LAMA2-CMD patients and 29.4% (5/17) of LGMD R23 patients, including 14 patients with epilepsy and 4 patients with febrile seizures. The median (range) age of first seizure episode was 5 (0.1-20) years in LAMA2-CMD and 14 (1-24) years in LGMD R23. Eight patients with epilepsy showed focal seizures. Abnormal results of electroencephalography were found in 8/10 patients, manifesting as temporal, occipital or temporo-occipital epileptiform abnormalities. Brain magnetic resonance imaging (MRI) was performed in 16 patients with seizures, showing occipital pachygyria in 4 patients, cerebellum and brain stem dysplasia in 2 patients. Brain MRI of 41 LAMA2-MD patients without seizures were reassessed, showing occipital lobe pachygyria in 6 patients. Therefore, there was no significant association between seizures and occipital pachygyria in our cohort (P=0.18). Nine patients received antiepileptic drugs, while patients with occipital lobe pachygyria showed poor seizure control. The pathogenic variants included splice mutation (n=8), nonsense mutation (n=6) and frameshift mutation(n=6) in LAMA2-CMD patients, while missense mutation (n=5), frameshift mutation(n=4) in LGMD R23 patients. Compared with LAMA2-CMD, seizures were more frequently occurred in LGMD R23 patients and mainly manifested as focal seizures. No correlation between genotype and seizures was observed. In this study, we found that seizures occurred in 10.5% of LAMA2-CMD and 29.4% of LGMD R23 patients, and described the features of seizures in LAMA2-MD patients.