Agochukwu Nneamaka B, Solomon Benjamin D, Muenke Maximilian
Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, NIH, MSC 3717, Building 35, Room 1B-207, Bethesda, MD 20892, USA.
Childs Nerv Syst. 2012 Sep;28(9):1447-63. doi: 10.1007/s00381-012-1756-2. Epub 2012 Aug 8.
More than 60 different mutations have been identified to be causal in syndromic forms of craniosynostosis. The majority of these mutations occur in the fibroblast growth factor receptor 2 gene (FGFR2). The clinical management of syndromic craniosynostosis varies based on the particular causal mutation. Additionally, the diagnosis of a patient with syndromic craniosynostosis is based on the clinical presentation, signs, and symptoms. The understanding of the hallmark features of particular syndromic forms of craniosynostosis leads to efficient diagnosis, management, and long-term prognosis of patients with syndromic craniosynostoses.
A comprehensive literature review was done with respect to the major forms of syndromic craniosynostosis and additional less common FGFR-related forms of syndromic craniosynostosis. Additionally, information and data gathered from studies performed in our own investigative lab (lab of Dr. Muenke) were further analyzed and reviewed. A literature review was also performed with regard to the genetic workup and diagnosis of patients with craniosynostosis.
Patients with Apert syndrome (craniosynostosis syndrome due to mutations in FGFR2) are most severely affected in terms of intellectual disability, developmental delay, central nervous system anomalies, and limb anomalies. All patients with FGFR-related syndromic craniosynostosis have some degree of hearing loss that requires thorough initial evaluations and subsequent follow-up.
Patients with syndromic craniosynostosis require management and treatment of issues involving multiple organ systems which span beyond craniosynostosis. Thus, effective care of these patients requires a multidisciplinary approach.
已确定60多种不同的突变是综合征性颅缝早闭的病因。这些突变大多数发生在成纤维细胞生长因子受体2基因（FGFR2）中。综合征性颅缝早闭的临床管理因具体的致病突变而异。此外，综合征性颅缝早闭患者的诊断基于临床表现、体征和症状。了解特定综合征性颅缝早闭形式的标志性特征有助于对综合征性颅缝早闭患者进行有效的诊断、管理和长期预后评估。
对综合征性颅缝早闭的主要形式以及其他不太常见的FGFR相关综合征性颅缝早闭形式进行了全面的文献综述。此外，对我们自己的研究实验室（Muenke博士的实验室）进行的研究收集的信息和数据进行了进一步分析和审查。还对颅缝早闭患者的基因检查和诊断进行了文献综述。
就智力残疾、发育迟缓、中枢神经系统异常和肢体异常而言，患有Apert综合征（由于FGFR2突变导致的颅缝早闭综合征）的患者受影响最为严重。所有FGFR相关综合征性颅缝早闭患者都有一定程度的听力损失，需要进行全面的初始评估和后续随访。
综合征性颅缝早闭患者需要对涉及多个器官系统的问题进行管理和治疗，这些问题超出了颅缝早闭的范围。因此，对这些患者进行有效护理需要采取多学科方法。
