Child Neurology and Psychiatry Unit, S Orsola Malpighi Hospital, University of Bologna, Bologna, Italy.
Am J Med Genet A. 2013 Feb;161A(2):273-84. doi: 10.1002/ajmg.a.35717. Epub 2013 Jan 15.
Mowat-Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene and is characterized by distinctive facial features, epilepsy, moderate to severe intellectual disability, corpus callosum abnormalities and other congenital malformations. Epilepsy is considered a main manifestation of the syndrome, with a prevalence of about 70-75%. In order to delineate the electroclinical phenotype of epilepsy in MWS, we investigated epilepsy onset and evolution, including seizure types, EEG features, and response to anti-epileptic therapies in 22 patients with genetically confirmed MWS. Onset of seizures occurred at a median age of 14.5 months (range: 1-108 months). The main seizure types were focal and atypical absence seizures. In all patients the first seizure was a focal seizure, often precipitated by fever. The semiology was variable, including hypomotor, versive, or focal clonic manifestations; frequency ranged from daily to sporadic. Focal seizures were more frequent during drowsiness and sleep. In 13 patients, atypical absence seizures appeared later in the course of the disease, usually after the age of 4 years. Epilepsy was usually quite difficult to treat: seizure freedom was achieved in nine out of the 20 treated patients. At epilepsy onset, the EEGs were normal or showed only mild slowing of background activity. During follow-up, irregular, diffuse frontally dominant and occasionally asymmetric spike and waves discharges were seen in most patients. Sleep markedly activated these abnormalities, resulting in continuous or near-to-continuous spike and wave activity during slow wave sleep. Slowing of background activity and poverty of physiological sleep features were seen in most patients. Our data suggest that a distinct electroclinical phenotype, characterized by focal and atypical absence seizures, often preceded by febrile seizures, and age-dependent EEG changes, can be recognized in most patients with MWS.
Mowat-Wilson 综合征（MWS）是一种由 ZEB2 基因突变或缺失引起的遗传疾病，其特征为独特的面部特征、癫痫、中度至重度智力障碍、胼胝体异常和其他先天性畸形。癫痫被认为是该综合征的主要表现，患病率约为 70-75%。为了描绘 MWS 中癫痫的电临床表型，我们研究了 22 例经基因证实的 MWS 患者的癫痫发作起始和演变，包括发作类型、脑电图特征和抗癫痫治疗反应。癫痫发作的起始中位年龄为 14.5 个月（范围：1-108 个月）。主要发作类型为局灶性和非典型失神发作。所有患者的首次发作均为局灶性发作，常由发热诱发。症状学多种多样，包括运动减少、扭转或局灶性阵挛表现；频率从每日到偶发不等。局灶性发作在困倦和睡眠时更频繁。在 13 例患者中，非典型失神发作在疾病后期出现，通常在 4 岁以后。癫痫通常很难治疗：20 例治疗患者中有 9 例达到无发作状态。在癫痫发作时，脑电图正常或仅显示背景活动轻度减慢。在随访过程中，大多数患者可见不规则、弥漫性额区优势、偶尔不对称的棘波和尖波放电。睡眠明显激活了这些异常，导致慢波睡眠期间出现连续或近乎连续的棘波和尖波活动。大多数患者可见背景活动减慢和生理性睡眠特征缺失。我们的数据表明，大多数 MWS 患者可识别出一种独特的电临床表型，特征为局灶性和非典型失神发作，常由热性惊厥引起，并且脑电图随年龄而变化。
