关键词: 无脑回-巨脑回畸形； 癫痫； PAFAH 1 B1 基因； TUBA1 A基因

Abstract: Objective To analyze the clinical and genetic characteristics of lissencephaly-pachygyria in children, and to perform genotype-phenotype analysis. Methods The clinical data of 60 children diagnosed with lissencephaly-pachygyria from January 2014 to March 2020 were collected, and next generation sequencing analysis was performed in 45 children and their parents. Results The onset age of 60 cases ( 30 males and 30 females) ranged from 2 days to 14 years old. Among 60 cases, 45 cases ( 75 %) were pachygyria, 4 cases ( 6 . 7 %) were lissencephaly, and 11 cases (18 . 3 %) were pachygyria with lissencephaly. Ten patients ( 16 . 7 %) had motor or language retardation as the onset symptom, and 48 patients ( 80 %) had epilepsy. Among them, 31 cases had spasm. During the follow-up period from 1 . 5 months to 5 years, among 50 patients with seizure, two cases of febrile seizure were seizure-free without treatment, 12 cases were seizure-free by treatment with antiepileptic drugs and 4 cases were seizure-free after epilepsy operation; 31 cases still had recurrent seizures; one case died of severe pneumonia. Among the 60 children, 59 had different degrees of psychomotor retardation, and 1 child (with onset age of 14 years) had normal development with focal pachygyria. Four mutations in PAFAH 1 B 1 /LIS 1 gene and one mutation in TUBA 1 A gene were found in 45 pedigrees. All the mutations were de novo and classified as pathogenic according to the American College of Medical Genetics and Genomics classification. Conclusions Most lissencephaly-pachygyria patients had refractory epilepsy, developmental retardation and poor prognosis. The first-line medication of epileptic spasm and epilepsy surgery may be beneficial to some patients. PAFAH 1 B 1 /LIS 1 gene and TUBA 1 A gene mutations were found in a few patients.

Key words: lissencephaly-pachygyria; epilepsy; PAFAH1B1 gene; TUBA 1 A gene