de Jong Tim, Mathijssen Irene M J, Hoogeboom A Jeannette M
Department of Plastic, Reconstructive and Hand Surgery, Erasmus MC, Sophia Children's Hospital, Rotterdam, the Netherlands.
J Craniofac Surg. 2011 Mar;22(2):571-5. doi: 10.1097/SCS.0b013e318207b761.
In about 30% of the patients with syndromal craniosynostosis, a genetic mutation can be traced. For the purpose of adequate genetic counseling and treatment of these patients, the full spectrum of clinical findings for each specific mutation needs to be appreciated. The Pro250Arg mutation in the FGFR3 gene is found in patients with Muenke syndrome and is one of the most frequently encountered mutations in craniosynostosis syndromes. A number of studies on the relationship between genotype and phenotype concerning this specific mutation have been published. Two Dutch families with Muenke syndrome were screened for the reported characteristics of this syndrome and for additional features. New phenotypical findings were hypoplasia of the frontal sinus, ptosis of the upper eyelids, dysplastic elbow joints with restricted elbow motion, and mild cutaneous syndactyly. Incidentally, polydactyly, severe ankylosis of the elbow, fusion of cervical vertebrae, and epilepsy were found. Upper eyelid ptosis is thought to be pathognomonic for Saethre-Chotzen syndrome but was also observed in our series of patients with Muenke syndrome. Because Muenke and Saethre-Chotzen syndrome can have similar phenotypes, DNA analysis is needed to distinguish between these syndromes, even when a syndrome diagnosis is already made in a family member.
在约30%的综合征性颅缝早闭患者中，可以追溯到基因突变。为了对这些患者进行充分的遗传咨询和治疗，需要了解每个特定突变的完整临床发现谱。FGFR3基因中的Pro250Arg突变见于穆恩克综合征患者，是颅缝早闭综合征中最常遇到的突变之一。关于这一特定突变的基因型与表型之间关系的多项研究已经发表。对两个患有穆恩克综合征的荷兰家庭进行了筛查，以了解该综合征的报告特征及其他特征。新的表型发现包括额窦发育不全、上睑下垂、肘关节发育异常伴肘部活动受限以及轻度皮肤并指。偶然发现多指、肘部严重强直、颈椎融合和癫痫。上睑下垂被认为是塞特雷-乔岑综合征的特征性表现，但在我们的穆恩克综合征患者系列中也观察到了。由于穆恩克综合征和塞特雷-乔岑综合征可能具有相似的表型，即使家族成员已经做出综合征诊断，也需要进行DNA分析以区分这些综合征。
