Doherty Emily S, Lacbawan Felicitas, Hadley Donald W, Brewer Carmen, Zalewski Christopher, Kim H Jeff, Solomon Beth, Rosenbaum Kenneth, Domingo Demetrio L, Hart Thomas C, Brooks Brian P, Immken Ladonna, Lowry R Brian, Kimonis Virginia, Shanske Alan L, Jehee Fernanda Sarquis, Bueno Maria Rita Passos, Knightly Carol, McDonald-McGinn Donna, Zackai Elaine H, Muenke Maximilian
National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Am J Med Genet A. 2007 Dec 15;143A(24):3204-15. doi: 10.1002/ajmg.a.32078.
Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene. Reduced penetrance and variable expressivity contribute to the wide spectrum of clinical findings in Muenke syndrome. To better define the clinical features of this syndrome, we initiated a study of the natural history of Muenke syndrome. To date, we have conducted a standardized evaluation of nine patients with a confirmed Pro250Arg mutation in FGFR3. We reviewed audiograms from an additional 13 patients with Muenke syndrome. A majority of the patients (95%) demonstrated a mild-to-moderate, low frequency sensorineural hearing loss. This pattern of hearing loss was not previously recognized as characteristic of Muenke syndrome. We also report on feeding and swallowing difficulties in children with Muenke syndrome. Combining 312 reported cases of Muenke syndrome with data from the nine NIH patients, we found that females with the Pro250Arg mutation were significantly more likely to be reported with craniosynostosis than males (P < 0.01). Based on our findings, we propose that the clinical management should include audiometric and developmental assessment in addition to standard clinical care and appropriate genetic counseling.
穆恩克综合征是一种常染色体显性疾病，其特征为冠状缝早闭、听力丧失、发育迟缓、腕骨和跗骨融合，以及FGFR3基因中存在Pro250Arg突变。外显率降低和表现度可变导致了穆恩克综合征临床表现的广泛差异。为了更好地界定该综合征的临床特征，我们启动了一项关于穆恩克综合征自然病史的研究。迄今为止，我们已对9名经证实FGFR3基因存在Pro250Arg突变的患者进行了标准化评估。我们还复查了另外13名穆恩克综合征患者的听力图。大多数患者（95%）表现为轻至中度低频感音神经性听力丧失。这种听力丧失模式以前未被认为是穆恩克综合征的特征。我们还报告了穆恩克综合征患儿的喂养和吞咽困难情况。将312例已报告的穆恩克综合征病例与来自美国国立卫生研究院的9名患者的数据相结合，我们发现携带Pro250Arg突变的女性比男性更易出现颅骨缝早闭（P < 0.01）。基于我们的研究结果，我们建议临床管理除了标准临床护理和适当的遗传咨询外，还应包括听力测定和发育评估。
