Clinical analysis of PAFAH1B1 gene variants in pediatric patients with epilepsy

• Published in: Seizure (London, England) England), 2024-04, Vol.117, p.98-104
• Main Authors: Feng, Wei-Xing, Wang, Xiao-Fei, Wu, Yun, Li, Xing-Meng, Chen, Shu-Hua, Wang, Xiao-Hui, Wang, Zi-Han, Fang, Fang, Chen, Chun-Hong
• Format: Article
• Language: English
• Subjects: 1-Alkyl-2-acetylglycerophosphocholine Esterase - genetics; Child; Child, Preschool; Developmental Disabilities - genetics; Developmental disability; Electroencephalography; Epilepsy; Epilepsy - genetics; Epilepsy - physiopathology; Female; Humans; Infant; Magnetic Resonance Imaging; Male; Microtubule-Associated Proteins; PAFAH1B1; Phenotype; Seizure
• ISSN: 1059-1311; 1532-2688
• DOI: 10.1016/j.seizure.2024.01.020

•PAFAH1B1, also known as LIS1, is associated with type I lissencephaly in humans, which is a severe developmental brain disorder believed to result from abnormal neuronal migration.•The aim of this present study is to elucidate the phenotypic presentations and molecular genetic characteristics of PAFAH1B1-related epilepsy in a Chinese cohort.•Notably, the clinical presentation in patients with PAFAH1B1 gene variants exhibits heterogeneity, and this heterogeneity is associated with the specific type of variant. PAFAH1B1, also known as LIS1, is associated with type I lissencephaly in humans, which is a severe developmental brain disorder believed to result from abnormal neuronal migration. Our objective was to characterize the genotypes and phenotypes of PAFAH1B1-related epilepsy. We conducted a comprehensive analysis of the medical histories, magnetic resonance imaging findings, and video-electroencephalogram recordings of 11 patients with PAFAH1B1 variants at the Neurology Department of Beijing Children's Hospital from June 2017 to November 2022. The age of onset of epilepsy ranged from 2 months to 4 years, with a median onset age of 5 months. Among these 11 patients (comprising 6 boys and 5 girls), all were diagnosed with lissencephaly type 1. Predominantly, generalized tonic-clonic and spasm seizures characterized PAFAH1B1-related epilepsy. Additionally, 10 out of the 11 patients exhibited severe developmental disorders. All patients exhibited de novo variants, with three individuals displaying 17p13.3 deletions linked to haploinsufficiency of PAFAH1B1. Four variants were previously unreported. Notably, three patients with 17p13.3 deletions displayed developmental delay and drug resistant epilepsy, whereas the single patient with mild developmental delay, Intelligence Quotient (IQ) 57 and well-controlled seizures had a splicing-site variant. The severity of the phenotype in patients with PAFAH1B1 variants ranged from drug-responsive seizures to severe epileptic encephalopathy. These observations underscore the clinical heterogeneity of PAFAH1B1-related disorders, with most patients exhibiting developmental disorders. Moreover, the severity of epilepsy appears to be linked to genetic variations.