Boycott Kym M, Parboosingh Jillian S, Scott James N, McLeod D Ross, Greenberg Cheryl R, Fujiwara T Mary, Mah Jean K, Midgley Julian, Wade Andrew, Bernier Francois P, Chodirker Bernard N, Bunge Martin, Innes A Micheil
Department of Medical Genetics, Alberta Children's Hospital and University of Calgary, Calgary, Alberta, Canada.
Am J Med Genet A. 2007 Aug 1;143A(15):1715-25. doi: 10.1002/ajmg.a.31832.
Meckel syndrome (MKS) is a rare lethal autosomal recessive disorder characterized by the presence of occipital encephalocele, cystic kidneys, fibrotic changes of the liver and polydactyly. Joubert syndrome (JS)-related disorders (JSRDs) or cerebello-oculo-renal syndromes (CORS) are a group of recessively inherited conditions characterized by a molar tooth sign (MTS) on cranial MRI, a set of core clinical features (developmental delay/mental retardation, hypotonia, ataxia, episodic breathing abnormalities, abnormal eye movements) and variable involvement of other systems including renal, ocular, central nervous system, craniofacial, hepatic, and skeletal. A significant clinical overlap between MKS and JSRD/CORS has been recognized in the literature. We describe a group of 10 Hutterite patients, of which 7 had been previously diagnosed with MKS, with a JSRD. Clinical features include variable early mortality, cognitive handicap, a characteristic dysmorphic facial appearance, hypotonia, ataxia, abnormal breathing pattern, nystagmus, and MTS on MRI. Additional features include occipital encephalocele, posterior fossa fluid collections resembling Dandy-Walker malformation, hydrocephalus, coloboma, and renal disease. This JSRD is a recognizable dysmorphic syndrome characterized by hypertelorism, deep-set eyes, down-slanting palpebral fissures, ptosis, arched eyebrows with medial sparseness, square nasal tip, short philtrum with tented upper lip, open mouth with down-turned corners, and posteriorly rotated low-set ears. Renal disease is present in 70% of patients and is characterized by cystic kidneys, abnormalities in renal function and hypertension. Homozygous deletions of NPHP1 and the known loci for JS/JSRD and MKS were excluded by identity-by-descent mapping studies suggesting that this condition in the Hutterites represents yet another locus for a JSRD.
梅克尔综合征（MKS）是一种罕见的致死性常染色体隐性疾病，其特征为枕部脑膨出、多囊肾、肝脏纤维化改变和多指（趾）畸形。乔伯特综合征（JS）相关疾病（JSRDs）或小脑-眼-肾综合征（CORS）是一组隐性遗传疾病，其特征为头颅磁共振成像（MRI）上的磨牙征（MTS）、一系列核心临床特征（发育迟缓/智力障碍、肌张力减退、共济失调、发作性呼吸异常、异常眼球运动）以及其他系统（包括肾脏、眼睛、中枢神经系统、颅面、肝脏和骨骼）的不同程度受累。文献中已认识到MKS与JSRD/CORS之间存在显著的临床重叠。我们描述了一组10名哈特派患者，其中7名先前被诊断为MKS，现患有JSRD。临床特征包括早期死亡率各异、认知障碍、特征性的面部畸形外观、肌张力减退、共济失调、异常呼吸模式、眼球震颤以及MRI上的MTS。其他特征包括枕部脑膨出、类似丹迪-沃克畸形的后颅窝积液、脑积水、虹膜缺损和肾脏疾病。这种JSRD是一种可识别的畸形综合征，其特征为眼距增宽、眼深陷、睑裂向下倾斜、上睑下垂、眉弓呈拱形且内侧稀疏、鼻尖呈方形、人中短且上唇呈帐篷状、口角向下的开口嘴以及低位后旋耳。70%的患者存在肾脏疾病，其特征为多囊肾、肾功能异常和高血压。通过同源性定位研究排除了NPHP1以及已知的JS/JSRD和MKS基因座的纯合缺失，这表明哈特派人群中的这种疾病代表了JSRD的另一个基因座。
