Understanding craniosynostosis as a growth disorder.
Understanding craniosynostosis as a growth disorder.
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DOI：
10.1002/wdev.227
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发表时间：
2016-07
期刊：
影响因子：
--
通讯作者：
Richtsmeier JT
中科院分区：
文献类型：
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作者：
Flaherty K;Singh N;Richtsmeier JT
颅缝闭闭是一种病因复杂的疾病，通常涉及一条或多条颅缝的过早融合，包括头部软硬组织的各种异常。该领域的稳步进展已导致识别反复引起颅缝闭闭的基因突变。尽管大多数非综合征性病例的遗传基础尚不清楚，但现在有许多基因突变与颅缝闭锁综合征有因果关系。这些基因突变的鉴定使我们在理解颅骨缝合线的内在特性方面取得了重大进展，包括正常缝合线通畅的机制和过早缝合的发病机制。了解颅穹窿缝合线的形态发生对于理解颅缝闭合的病理生理至关重要，但该领域现在准备认识到通常伴随过早缝合线闭合的头部其他骨骼和软组织的重复变化。我们回顾了在我们的范围内对过早缝合闭合的理解的研究。然后，我们列举了研究较少，但同样具有挑战性的，在现有小鼠模型中具有良好特征的颅缝闭合条件的非缝合线表型。我们认为颅缝闭闭是发育中的头部多组织的复杂生长障碍，其生长也被确定的突变靶向，其方式尚不清楚。从这些疾病的人类和小鼠模型的研究中获得的知识强调了头部的多样性，相关的发育异常，这些异常有助于颅缝闭闭疾病的复杂表型，为未来的研究提出了新的挑战。
Craniosynostosis is a condition of complex etiology that always involves the premature fusion of one or multiple cranial sutures and includes various anomalies of the soft and hard tissues of the head. Steady progress in the field has resulted in identifying gene mutations that recurrently cause craniosynostosis. There are now scores of mutations on many genes causally related to craniosynostosis syndromes, though the genetic basis for the majority of nonsyndromic cases is unknown. Identification of these genetic mutations has allowed significant progress in understanding the intrinsic properties of cranial sutures, including mechanisms responsible for normal suture patency and for pathogenesis of premature suture closure. An understanding of morphogenesis of cranial vault sutures is critical to understanding the pathophysiology of craniosynostosis conditions, but the field is now poised to recognize the repeated changes in additional skeletal and soft tissues of the head that typically accompany premature suture closure. We review the research that has brought an understanding of premature suture closure within our reach. We then enumerate the less well-studied, but equally challenging, non-sutural phenotypes of craniosynostosis conditions that are well-characterized in available mouse models. We consider craniosynostosis as a complex growth disorder of multiple tissues of the developing head, whose growth is also targeted by identified mutations in ways that are poorly understood. Knowledge gained from studies of humans and mouse models for these conditions underscores the diverse, associated developmental anomalies of the head that contribute to the complex phenotypes of craniosynostosis conditions presenting novel challenges for future research.