Developmental anomalies of the cervical spine in patients with fibrodysplasia ossificans progressiva are distinctly different from those in patients with Klippel-Feil syndrome - Clues from the BMP signaling pathway
Developmental anomalies of the cervical spine in patients with fibrodysplasia ossificans progressiva are distinctly different from those in patients with Klippel-Feil syndrome - Clues from the BMP signaling pathway
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DOI：
10.1097/01.brs.0000166619.22832.2c
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发表时间：
2005-06-15
期刊：
影响因子：
3
通讯作者：
Kusumi, K
中科院分区：
文献类型：
--
作者：
Schaffer, AA;Kaplan, FS;Kusumi, K
研究设计.对70例诊断为进行性骨化性纤维发育不良（FOP）和33例诊断为Klippel-Feil（KF）综合征的患者进行颈椎X线分析。本研究的目的是描述FOP患者的颈椎异常，将这些发现与KF综合征患者的畸形进行比较和对比，并检查这些异常的可能病因。疾病的先天性特征通常为潜在病因学和发育途径提供重要线索。虽然结缔组织向异位骨的进行性变态是FOP最引人注目和致残的特征，但也存在不太严重的骨骼先天性异常。KF中观察到的椎体融合与胚胎分割缺陷一致。对70例FOP和33例KF患者的颈椎平片进行回顾性分析。在大多数FOP儿童中，普遍的颈部僵硬和活动范围减少。在FOP患者组中，观察到特征性异常，包括较大的后部结构、高而窄的椎体以及C2和C7之间的小关节融合。最值得注意的是，FOP患者颈椎的这些特征性异常明显不同于33例KF患者，但与编码noggin（一种骨形态发生蛋白（BMP）拮抗剂）的基因纯合缺失的小鼠中观察到的异常惊人相似。FOP患者表现出一组特征性的先天性脊柱畸形。虽然头蛋白基因（NOG）在FOP患者中没有突变，但这些发现扩展了越来越多的证据，表明BMP信号通路在FOP的分子发病机制中过度活跃。
Study Design. A radiographic analysis of the cervical spine of 70 patients diagnosed with fibrodysplasia ossificans progressiva (FOP) and 33 diagnosed with Klippel-Feil (KF) syndrome was conducted.Objectives. The objectives of this study were to describe cervical spine abnormalities in patients with FOP, to compare and contrast those findings with the malformations in patients with KF syndrome, and to examine the possible etiology of these abnormalities.Summary of Background Data. Congenital features of diseases often provide seminal clues to underlying etiology and developmental pathways. While progressive metamorphosis of connective tissue to heterotopic bone is the most dramatic and disabling feature of FOP, less severe congenital anomalies of the skeleton are also present. Vertebral fusions observed in KF are consistent with defects in embryonic segmentation.Methods. The cervical spine plain films of 70 FOP patients and 33 KF patients with documented congenital abnormalities were reviewed.Results. Generalized neck stiffness and decreased range of motion were noted in most children with FOP. In the FOP patient group, characteristic anomalies, including large posterior elements, tall narrow vertebral bodies, and fusion of the facet joints between C2 and C7, were observed. Most notably, these characteristic anomalies of the cervical spine in patients with FOP were distinctly different from those of 33 patients with KF that were examined but were strikingly similar to those seen in mice with homozygous deletions of the gene-encoding noggin, a bone morphogenetic protein (BMP) antagonist.Conclusions. FOP patients exhibit a characteristic set of congenital spine malformations. While the noggin gene (NOG) is not mutated in patients who have FOP, these findings extend a growing body of evidence implicating overactivity of the BMP signaling pathway in the molecular pathogenesis of FOP.