PDF(Pubmed)
Abstract：
BACKGROUND Short stature is the second most common reason for referral to a pediatric endocrinology clinic. Numerous genetic causes have been identified. Weill-Marchesani syndrome (WMS) is one of the rare genetic disorders that cause short stature. It is caused by homozygous mutations in the FBN1 gene, ADAMTS10 gene, ADAMTS17 gene, or LTBP2 gene. Despite genetic heterogeneity, WMS is clinically homogeneous. It is characterized by short stature, brachydactyly, joint stiffness, ocular abnormalities, mainly microspherophakia and glaucoma, and occasionally cardiac defects. CASE REPORT A 9-year-old boy had bilateral narrow-angle glaucoma with lens subluxation, elevated intraocular pressure, and severe myopia since early childhood. He had phenotypic dysmorphic features and radiological findings consistent with WMS. He underwent lensectomy and scleral-fixated intraocular lens implantation as well as drug treatment to control the intraocular pressure. He was a slow grower, and his growth parameters showed disproportionate short stature with brachydactyly and joint stiffness. Growth hormone provocation tests were subnormal with a peak value of 7.89 ng/mL. CONCLUSIONS The constellation of clinical presentation, radiological findings, and the molecular examination confirmed a homozygous familial variant of the ADAMTS10 gene identified by carrier gene testing. This known familial variant creates a premature termination codon classified as a likely pathogenic cause of WMS. In this syndrome, glaucoma treatment is considered the greatest challenge. The disease-causing mechanism in WMS is not known but thought to be due to abnormal actin distribution and organization in fibroblasts as a result of impaired connections between extracellular matrix components and the cytoskeleton.
摘要：
背景技术身材矮小是转诊至儿科内分泌学诊所的第二最常见原因。已经确定了许多遗传原因。Weill-Marchesani综合征（WMS）是导致身材矮小的罕见遗传疾病之一。它是由FBN1基因的纯合突变引起的，ADAMTS10基因,ADAMTS17基因,或LTBP2基因。尽管遗传异质性，WMS是临床均一的。它的特点是身材矮小，Brachydactyly,接头刚度,眼部异常，主要是微球和青光眼，偶尔还有心脏缺陷.病例报告一名9岁男孩患有双侧窄角型青光眼伴晶状体半脱位，眼内压升高，和儿童早期的严重近视。他的表型畸形特征和放射学发现与WMS一致。他接受了晶状体切除术和巩膜固定人工晶状体植入术以及药物治疗以控制眼压。他是个生长缓慢的人，他的生长参数显示出不成比例的身材矮小，短指和关节僵硬。生长激素激发试验低于正常，峰值为7.89ng/mL。结论临床表现的星座，放射学发现，分子检查证实了通过载体基因检测鉴定的ADAMTS10基因的纯合家族变体。这种已知的家族性变体产生被分类为WMS的可能致病原因的过早终止密码子。在这种综合症中，青光眼治疗被认为是最大的挑战。WMS中的致病机制尚不清楚，但认为是由于细胞外基质成分与细胞骨架之间的连接受损，成纤维细胞中的肌动蛋白分布和组织异常。
