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.

中文翻译：

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自限性局灶性癫痫和儿童言语失用伴 WAC 致病变异

杂合致病性 WAC 变异导致 Desanto-Shinawi 综合征；受影响的患者有畸形特征、发育障碍和行为异常。四分之一报告癫痫发作，包括强直阵挛、失神和热性惊厥。本研究旨在更好地了解 Desanto-Shinawi 综合征中癫痫和发展的表型谱。我们确定了四名患有癫痫发作和致病性 WAC 变异的儿童，包括两个兄弟姐妹。所有人都有整体发育障碍，语言受影响最严重；两人被诊断为儿童言语失用症，两人患有自闭症谱系障碍。癫痫发作年龄从 6 个月到 14 岁不等。癫痫发作总是在睡眠中发生，并且有 3 名患者的运动特征的局灶性意识障碍，其中一个有疑似局灶性发作的双侧强直阵挛发作。两名患者在未经治疗的情况下自发性发作消退，其余两名患者在单药治疗后控制良好。2 例患者脑电图正常；一个在困倦和睡眠中具有局灶性右额叶尖峰，而最后一个在两个半球都有独立的中央颞尖峰，在睡眠中被激活。所有患者均具有杂合截短的致病性 WAC 变异，父母测试呈阴性。这组患者的研究结果表明，Desanto-Shinawi 综合征中的癫痫通常是局灶性和自限性的，可能属于癫痫-失语症谱。一个在困倦和睡眠中具有局灶性右额叶尖峰，而最后一个在两个半球都有独立的中央颞尖峰，在睡眠中被激活。所有患者均具有杂合截短的致病性 WAC 变异，父母测试呈阴性。这组患者的研究结果表明，Desanto-Shinawi 综合征中的癫痫通常是局灶性和自限性的，可能属于癫痫-失语症谱。一个在困倦和睡眠中具有局灶性右额叶尖峰，而最后一个在两个半球都有独立的中央颞尖峰，在睡眠中被激活。所有患者均具有杂合截短的致病性 WAC 变异，父母测试呈阴性。这组患者的研究结果表明，Desanto-Shinawi 综合征中的癫痫通常是局灶性和自限性的，可能属于癫痫-失语症谱。