Myers Kenneth A, White Susan M, Mohammed Shehla, Metcalfe Kay A, Fry Andrew E, Wraige Elisabeth, Vasudevan Pradeep C, Balasubramanian Meena, Scheffer Ingrid E
Department of Pediatrics, Faculty of Medicine, McGill University, Montreal, Quebec, Canada; Division of Child Neurology, Montreal Children's Hospital, McGill University Health Centre, 1001 Décarie Blvd., Montreal, Quebec, H4A 3J1, Canada; Epilepsy Research Centre, Department of Medicine, The University of Melbourne, Austin Health, Heidelberg, Victoria, 3084, Australia.
Victorian Clinical Genetics Service, Murdoch Children's Research Institute, 50 Flemington Road, Parkville, Victoria, 3052, Australia; Department of Paediatrics, The University of Melbourne, 50 Flemington Road, Parkville, Victoria, 3052, Australia.
Epilepsy Res. 2018 Feb;140:166-170. doi: 10.1016/j.eplepsyres.2018.01.014. Epub 2018 Feb 3.
Bainbridge-Ropers syndrome is a genetic syndrome caused by heterozygous loss-of-function pathogenic variants in ASXL3, which encodes a protein involved in transcriptional regulation. Affected individuals have multiple abnormalities including developmental impairment, hypotonia and characteristic facial features. Seizures are reported in approximately a third of cases; however, the epileptology has not been thoroughly studied. We identified three patients with pathogenic ASXL3 variants and seizures at Austin Health and in the DECIPHER database. These three patients had novel de novo ASXL3 pathogenic variants, two with truncation variants and one with a splice site variant. All three had childhood-onset generalized epilepsy with generalized tonic-clonic seizures, with one also having atypical absence seizures. We also reviewed available clinical data on five published patients with Bainbridge-Ropers syndrome and seizures. Of the five previously published patients, three also had generalized tonic-clonic seizures, one of whom also had possible absence seizures; a fourth patient had absence seizures and possible focal seizures. EEG typically showed features consistent with generalized epilepsy including generalized spike-wave, photoparoxysmal response, and occipital intermittent rhythmic epileptiform activity. Bainbridge-Ropers syndrome is associated with childhood-onset generalized epilepsy with generalized tonic-clonic seizures and/or atypical absence seizures.
班布里奇-罗佩斯综合征是一种由ASXL3基因杂合功能丧失性致病变异引起的遗传综合征，ASXL3基因编码一种参与转录调控的蛋白质。受影响的个体有多种异常表现，包括发育障碍、肌张力减退和特征性面部特征。约三分之一的病例有癫痫发作的报道；然而，癫痫学方面尚未得到充分研究。我们在奥斯汀健康中心和DECIPHER数据库中识别出3例携带ASXL3致病变异且有癫痫发作的患者。这3例患者有新的ASXL3基因新生致病变异，其中2例为截短变异，1例为剪接位点变异。3例患者均为儿童期起病的全面性癫痫，伴有全面性强直阵挛发作，其中1例还伴有不典型失神发作。我们还回顾了5例已发表的患有班布里奇-罗佩斯综合征且有癫痫发作患者的现有临床资料。在这5例先前发表的患者中，3例也有全面性强直阵挛发作，其中1例还可能有失神发作；第4例患者有失神发作和可能的局灶性发作。脑电图通常显示与全面性癫痫一致的特征，包括全面性棘波、光阵发性反应和枕叶间歇性节律性癫痫样活动。班布里奇-罗佩斯综合征与儿童期起病的全面性癫痫伴全面性强直阵挛发作和/或不典型失神发作有关。
