Adam Margaret P, Schelley Susan, Gallagher Renata, Brady April N, Barr Kimberly, Blumberg Bruce, Shieh Joseph T C, Graham John, Slavotinek Anne, Martin Madelena, Keppler-Noreuil Kim, Storm Andrea L, Hudgins Louanne
Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
Am J Med Genet A. 2006 Dec 15;140(24):2730-41. doi: 10.1002/ajmg.a.31530.
Mowat-Wilson syndrome (MWS) is a relatively newly described multiple congenital anomaly/mental retardation syndrome. Haploinsufficiency of a gene termed ZFHX1B (also known as SIP1) on chromosome 2 is responsible for this condition, and clinical genetic testing for MWS recently became available. The majority of reports in the literature originate from Northern Europe and Australia. Here we report our clinical experience with 12 patients diagnosed with MWS within a 2-year period of time in the United States, with particular emphasis on clinical characteristics and management strategies. Individuals with this condition have characteristic facial features, including microcephaly, hypertelorism, medially flared and broad eyebrows, prominent columella, pointed chin, and uplifted earlobes, which typically prompt the clinician to consider the diagnosis. Medical issues in our cohort of patients included seizures (75%) with no predeliction for any particular seizure type; agenesis of the corpus callosum (60% of our patients studied); congenital heart defects (75%), particularly involving the pulmonary arteries and/or valves; hypospadias (55% of males); severely impaired or absent speech (100% of individuals over 1 year of age) with relatively spared receptive language; and Hirschsprung disease (50%) or chronic constipation (25%). The incidence of MWS is unknown, but based on the number of patients identified in a short period of time within the US, it is likely greatly under recognized. MWS should be considered in any individual with severely impaired or absent speech, especially in the presence of seizures and anomalies involving the pulmonary arteries (particularly pulmonary artery sling) or pulmonary valves.
莫瓦特-威尔逊综合征（MWS）是一种相对较新描述的多发性先天性异常/智力发育迟缓综合征。2号染色体上一个名为ZFHX1B（也称为SIP1）的基因单倍剂量不足导致了这种疾病，最近针对MWS的临床基因检测已经可用。文献中的大多数报告来自北欧和澳大利亚。在此，我们报告在美国2年时间内诊断出的12例MWS患者的临床经验，特别强调临床特征和管理策略。患有这种疾病的个体具有特征性的面部特征，包括小头畸形、眼距过宽、眉毛向内侧展开且宽阔、鼻小柱突出、下巴尖以及耳垂上翘，这些特征通常促使临床医生考虑进行诊断。我们患者队列中的医学问题包括癫痫发作（75%），对任何特定癫痫类型均无偏好；胼胝体发育不全（在我们研究的患者中占60%）；先天性心脏缺陷（75%），尤其涉及肺动脉和/或瓣膜；尿道下裂（男性患者中占55%）；严重言语受损或无言语能力（1岁以上个体中占100%），而接受性语言相对保留；以及先天性巨结肠（50%）或慢性便秘（25%）。MWS的发病率尚不清楚，但基于在美国短时间内确诊的患者数量，很可能未得到充分认识。对于任何严重言语受损或无言语能力的个体，尤其是伴有癫痫发作以及涉及肺动脉（特别是肺动脉吊带）或肺动脉瓣异常的个体，都应考虑MWS。
