Division of Child Neurology, Department of Pediatrics, Montreal Children's Hospital, McGill University, Montreal, Quebec, Canada.
Department of Paediatrics, Royal Children's Hospital, The University of Melbourne, Flemington, Victoria, Australia; Speech and Language, Murdoch Children's Research Institute, Royal Children's Hospital, Flemington, Victoria, Australia.
Eur J Paediatr Neurol. 2021 Jan;30:25-28. doi: 10.1016/j.ejpn.2020.12.010. Epub 2020 Dec 24.
Heterozygous pathogenic WAC variants cause Desanto-Shinawi syndrome; affected patients have dysmorphic features, developmental impairment and behavioral abnormalities. Seizures are reported in one quarter, including tonic-clonic, absence, and febrile seizures. This study aimed to better understand the phenotypic spectrum of epilepsy and development in Desanto-Shinawi syndrome. We identified four children with seizures and pathogenic WAC variants, including two siblings. All had global developmental impairment with language affected most severely; two had diagnoses of childhood apraxia of speech and two had autism spectrum disorder. Seizure onset age ranged from six months to 14 years. Seizures always occurred from sleep and were focal impaired awareness with motor features in three patients, with one having bilateral tonic-clonic seizures of suspected focal onset. Two patients had spontaneous seizure resolution without treatment, and the remaining two were well-controlled on monotherapy. EEG was normal in two patients; one had focal right frontal spikes in drowsiness and sleep while the last had independent centrotemporal spikes from both hemispheres, activated in sleep. All patients had heterozygous truncating pathogenic WAC variants, with negative parental testing. The findings in this cohort of patients suggest that epilepsy in Desanto-Shinawi syndrome is usually focal and self-limited, and may fall within the epilepsy-aphasia spectrum.
杂合致病性 WAC 变异导致 Desanto-Shinawi 综合征；受影响的患者具有发育障碍和行为异常的特征。四分之一的患者报告有癫痫发作，包括强直-阵挛发作、失神发作和热性惊厥。本研究旨在更好地了解 Desanto-Shinawi 综合征中癫痫和发育的表型谱。我们确定了四个有癫痫发作和致病性 WAC 变异的儿童，包括两个兄弟姐妹。所有患者均有全面发育障碍，语言障碍最严重；两个患者有儿童言语运动性失用症的诊断，两个患者有自闭症谱系障碍。癫痫发作的起始年龄从 6 个月到 14 岁不等。癫痫发作总是在睡眠中发生，且具有局灶性意识障碍和运动特征，三名患者中有一名患者疑似局灶性起源的双侧强直-阵挛发作。两名患者自发缓解，无需治疗，其余两名患者单药治疗控制良好。两名患者的脑电图正常；一名患者在困倦和睡眠时出现右侧额部棘波，另一名患者则有来自两个半球的独立中央颞区棘波，在睡眠时激活。所有患者均携带杂合截断致病性 WAC 变异，父母检测结果均为阴性。本患者队列的研究结果表明，Desanto-Shinawi 综合征中的癫痫通常为局灶性和自限性的，可能属于癫痫-失语症谱。
