A Korean family with the Muenke syndrome

Abstract

The Muenke syndrome (MS) is characterized by unicoronal or bicoronal craniosynostosis, midfacial hypoplasia, ocular hypertelorism, and a variety of minor abnormalities associated with a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. The birth prevalence is approximately one in 10,000 live births, accounting for 8-10% of patients with coronal synostosis. Although MS is a relatively common diagnosis in patients with craniosynostosis syndromes, with autosomal dominant inheritance, there has been no report of MS, in an affected Korean family with typical cephalo-facial morphology that has been confirmed by molecular studies. Here, we report a familial case of MS in a female patient with a Pro250Arg mutation in exon 7 (IgII-IGIII linker domain) of the FGFR3 gene. This patient had mild midfacial hypoplasia, hypertelorism, downslanting palpebral fissures, a beak shaped nose, plagio-brachycephaly, and mild neurodevelopmental delay. The same mutation was confirmed in the patient's mother, two of the mother's sisters and the maternal grandfather. The severity of the cephalo-facial anomalies was variable among these family members.

Keywords: Autosomal Dominant; FGF3 Gene Mutation; Muenke Syndrome.

Fig. 1

Clinical and radiological features of a patient with the Muenke syndrome and FGFR3 mutation. (A) A 24 month-old girl with Pro250Arg shows mild exophthalmos and plagio-brachycephaly. (B) Both coronal sutures are completely fused. (C) Proptosis and a small cerebellum were present on the sagittal view of the MR-T1WI.

Fig. 2

Photography and family pedigree. (A) The patient and her mother with a Pro250Arg mutation. The mother also had mild midfacial hypoplasia, hypertelorism, and downslanting palpebral fissures. (B) Pedigree of the family with Muenke syndrome demonstrates an autosomal dominant inheritance.

Fig. 3

DNA sequencing showed a heterozygous mutation in the patient (C to G) of FGFR3 in exon 7. This mutation caused an amino acid substitution of arginine (CGG) for proline (CCG) [p.Pro250Arg, c.749 C>G)].