PDF(Pubmed)
Abstract：
Congenital arthrogryposis (CA) refers to the presence of multiple contractures at birth. It is a feature of several inherited syndromes, notable amongst them are disorders of collagen formation. This review aims to characterize disorders that directly or indirectly impact collagen structure and function leading to CA in search for common phenotypic or pathophysiological features, possible genotype-phenotype correlation, and potential novel treatment approaches based on a better understanding of the underlying pathomechanism. Nine genes, corresponding to five clinical phenotypes, were identified after a literature search. The most notable trend was the extreme phenotype variability. Clinical features across all syndromes ranged from subtle with minimal congenital contractures, to severe with multiple congenital contractures and extra-articular features including skin, respiratory, or other manifestations. Five of the identified genes were involved in the function of the Lysyl Hydroxylase 2 or 3 enzymes, which enable the hydroxylation and/or glycosylation of lysyl residues to allow the formation of the collagen superstructure. Whilst current treatment approaches are post-natal surgical correction, there are also potential in-utero therapies being developed. Cyclosporin A showed promise in treating collagen VI disorders although there is an associated risk of immunosuppression. The treatments that could be in the clinical trials soon are the splice correction therapies in collagen VI-related disorders.
摘要：
先天性关节病（CA）是指在出生时存在多个挛缩。它是几种遗传综合征的特征，其中值得注意的是胶原蛋白形成障碍。这篇综述旨在描述直接或间接影响胶原蛋白结构和功能的疾病，以寻找常见的表型或病理生理学特征。可能的基因型-表型相关性，以及基于对潜在病理机制的更好理解的潜在新颖治疗方法。九个基因,对应于五种临床表型，是在文献检索后确定的。最显着的趋势是极端的表型变异性。所有综合征的临床特征都包括轻微的先天性挛缩，严重的多发性先天性挛缩和关节外特征，包括皮肤，呼吸,或其他表现。5个鉴定的基因参与赖氨酰羟化酶2或3酶的功能，这使得赖氨酰残基的羟基化和/或糖基化能够形成胶原超结构。虽然目前的治疗方法是产后手术矫正，还有潜在的子宫内疗法正在开发中。尽管存在相关的免疫抑制风险，但环孢菌素A在治疗VI型胶原疾病中显示出希望。即将进行临床试验的治疗方法是VI型胶原相关疾病中的剪接校正疗法。
