Muenke syndrome is a craniosynostosis syndrome associated with the p.Pro250Arg mutation in FGFR3. An increasing number of individuals with this mutation are reported to not have craniosynostosis. The purpose of this report is to increase awareness of the high phenotypic variability seen in Muenke syndrome. DNA testing for the p.Pro250Arg mutation is routinely performed in Denmark, in children presenting with isolated coronal synostosis. Verified diagnosis entails detailed family history, drawing of family pedigree, DNA testing of the parents, genetic counseling, skull radiographs, clinical photographs, and follow-up. Sixteen individuals from 5 Danish families with Muenke syndrome are presented. Large phenotypic variation was seen both within and across families. The most striking observations were that 6/16 (38%) cases did not have craniosynostosis and one individual presented with a normal phenotype. In addition, 3 unrelated cases had incomplete cleft palate, submucous cleft palate, and bifid uvula, respectively. There is strong evidence for reduced penetrance of the craniosynostosis trait in Muenke syndrome. We argue that many studies on Muenke syndrome have been influenced by ascertainment bias in regard to craniosynostosis. In addition, it is suggested that oral clefting might be part of the clinical spectrum seen in Muenke syndrome.

中文翻译：

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来自五个丹麦家庭的Muenke综合征的表型变异性。

Muenke综合征是与FGFR3中的p.Pro250Arg突变相关的颅突综合征。据报道，越来越多的人患有这种突变，没有颅骨突触。本报告的目的是提高人们对在Muenke综合征中发现的高表型变异性的认识。p.Pro250Arg突变的DNA测试通常在丹麦进行，以表现为孤立的冠状突触。经过验证的诊断包括详细的家族史，家族谱系图，父母的DNA测试，遗传咨询，颅骨X线照片，临床照片和随访。介绍了来自5个丹麦家庭的Muenke综合征的16个人。在家庭内部和家庭之间都可以看到较大的表型变异。最明显的观察结果是6/16（38％）的病例没有颅骨前突并有一个表现正常的个体。此外，3例无关病例分别具有不完全的left裂，粘膜下裂和双裂悬雍垂。有强有力的证据表明，在Muenke综合征中，颅骨突触性状的外显率降低。我们认为，关于Muenke综合征的许多研究都受到有关颅骨突触症的确定性偏见的影响。另外，有人认为口腔裂口可能是在Muenke综合征中看到的临床症状的一部分。我们认为，关于Muenke综合征的许多研究都受到有关颅骨突触症的确定性偏见的影响。另外，有人认为口腔裂口可能是在Muenke综合征中看到的临床症状的一部分。我们认为，关于Muenke综合征的许多研究都受到有关颅骨前突的确定性偏见的影响。此外，有人认为口腔裂口可能是在Muenke综合征中看到的临床症状的一部分。