Clinical genetics and pathobiology of ciliary chondrodysplasias.
Clinical genetics and pathobiology of ciliary chondrodysplasias.
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睫状软骨浮肿的临床遗传学和病理学。
DOI：
10.3233/pge-14089
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发表时间：
2014-11
影响因子：
0.4
通讯作者：
Schmidts M
中科院分区：
文献类型：
--
作者：
Schmidts M
睫状软骨发育不良是一组罕见的、几乎完全是常染色体隐性遗传的发育疾病。虽然主要影响四肢、肋骨和有时影响颅面骨骼的骨骼表型占主导地位，但影响肾脏、肝脏、心脏、眼睛和其他器官和组织的皮肤外疾病的观察结果并不一致。在这些条件下观察到由胸部收缩引起的心肺衰竭以及由先天性心脏病引起的肾和肝功能不全或原发性心力衰竭引起的显著致死性。潜在的遗传缺陷以及使用动物模型系统进行的发育生物学和细胞生物学工作表明，这些罕见的疾病是由纤毛功能障碍引起的。骨骼表型被认为是由刺猬信号通路的不平衡引起的，该通路通常发生在软骨细胞的功能性纤毛中。虽然表型在历史上已根据临床特征区分为短肋多指（趾）综合征、Jeune窒息性胸营养不良、Mainzer-Saldino综合征、Sensenbrenner综合征（颅外胚层发育不良）、口面指综合征和Ellis-van Creveld综合征，但最近的研究表明，这些疾病之间存在显著的遗传和表型重叠。本文综述了睫状体软骨发育不良从表型特征到临床治疗的进展，并总结了潜在的分子机制以及未来的治疗前景。
Ciliary chondrodysplasias represent a heterogenous group of rare, nearly exclusively autosomal recessively inherited developmental conditions. While the skeletal phenotype, mainly affecting limbs, ribs and sometimes the craniofacial skeleton, is predominant, extraskeletal disease affecting the kidneys, liver, heart, eyes and other organs and tissues is observed inconsistently. Significant lethality, resulting from cardiorespiratory failure due to thoracic constriction as well as from renal and hepatic insufficiency or primary cardiac failure due to congenital heart disease, is observed with these conditions. The underlying genetic defects as well as developmental biology and cell biology work undertaken using animal model systems, suggest that these rare conditions result from ciliary malfunction. The skeletal phenotype is believed to result from imbalances in the hedgehog signaling pathway that normally occurs in functional cilia in chondrocytes. Although phenotypes have been historically distinguished based on clinical features into short-rib polydactyly syndrome, Jeune asphyxiating thoracic dystrophy, Mainzer-Saldino syndrome, Sensenbrenner syndrome (cranioectodermal dysplasia), oral-facial-digital syndrome and Ellis-van Creveld syndrome, recent research suggests that there is significant genetic as well as phenotypic overlap between the conditions. This review discusses ciliary chondrodysplasias from phenotypic hallmarks to clinical management and summarizes progress in identification of the underlying molecular mechanisms as well as potential future therapeutic perspectives.