Abstract
Background
Muenke syndrome is a genetically determined craniosynostosis that involves one or both coronal sutures. In some patients it is associated with skeletal abnormalities such as thimble-like middle phalanges, coned epiphysis, and/or neurological impairment, namely sensorineural hearing loss or mental retardation. In spite of a variable phenotype, Muenke syndrome has been related to a unique mutation on the FGFR3 gene, Pro 250 to Arg, which is characteristic of this disease. Because of the incomplete penetrance of this anomaly, the suspicion of Muenke syndrome must be raised in any child with uni- or bilateral coronal craniosynostosis, and the genetic analysis propounded even in the absence of extracranial features.
Illustrative cases
We report the cases of two sisters who presented with Muenke syndrome and whose affected mother did not have any form of craniosynostosis.
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References
Bellus GA, Gaudenz K, Zackai EH, Clarke LA, Szabo J, Francomano CA, Muenke M (1996) Identical mutations in three different fibroblast growth factor receptor genes in autosomal dominant craniosynostosis syndromes. Nat Genet 14:174–176
Cassileth LB, Bartlett SP, Glat PM, Gripp KW, Muenke M, Zackai EH, Whitaker LA (2001) Clinical characteristics of patients with unicoronal synostosis and mutations of fibroblast growth factor receptor 3: a preliminary report. Plast Reconstr Surg 108:1849–1854
Golla A, Lichtner P, von Gernet S, Winterpacht A, Fairley J, Murken J, Schuffenhauer S (1997) Phenotypic expression of the fibroblast growth factor receptor 3 (FGFR3) mutation P250R in a large craniosynostosis family. J Med Genet 34:683–684
Graham JM Jr, Braddock SR, Mortier GR, Lachman R, Van Dop C, Jabs EW (1998) Syndrome of coronal craniosynostosis with brachydactyly and carpal/tarsal coalition due to Pro250Arg mutation in FGFR3 gene. Am J Med Genet 77:322–329
Gripp KW, McDonald-McGinn DM, Gaudenz K, Whitaker LA, Bartlett SP, Glat PM, Cassileth LB, Mayro R, Zackai EH, Muenke M (1998) Identification of a genetic cause for isolated unilateral coronal synostosis: a unique mutation in the fibroblast growth factor receptor 3. J Pediatr 132:714–716
Grosso S, Farnetani MA, Berardi R, Bartalini G, Carpentieri M, Galluzzi P, Mostardini R, Morgese G, Balestri P (2003) Medial temporal lobe dysgenesis in Muenke syndrome and hypochondroplasia. Am J Med Genet 120:88–91
Hehr U, Muenke M (1999) Craniosynostosis syndromes: from genes to premature fusion of skull bones. Mol Genet Metab 68:139–151
Hollway GE, Suthers GK, Battese KM, Turner AM, David DJ, Mulley JC (1998) Deafness due to pro250-to-arg mutation of FGFR3. Lancet 351:877–878
Lajeunie E, El Ghouzzi V, Le Merrer M, Munnich A, Bonaventure J, Renier D (1999) Sex related expressivity of the phenotype in coronal craniosynostosis caused by the recurrent P250R FGFR3 mutation. J Med Genet 36:9–13
Moloney DM, Wall SA, Ashworth GJ, Oldridge M, Glass IA, Francomano CA, Muenke M, Wilkie AO (1997) Prevalence of Pro250Arg mutation of fibroblast growth factor receptor 3 in coronal craniosynostosis. Lancet 349:1059–1062
Muenke M, Gripp KW, McDonald-McGinn DM, Gaudenz K, Whitaker LA, Bartlett SP, Markowitz RI, Robin NH, Nwokoro N, Mulvihill JJ, Losken W, Mulliken JB, Guttmacher AE, Wilroy RS, Clarke LA, Hollway G, Ades LC, Haan EA, Mulley JC, Cohen MM Jr, Bellus GA, Francomano CA, Moloney DM, Wall SA, Wilkie AOM, Zackai EH (1997) A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome. Am J Hum Genet 60:555–564
Mulliken JB, Steinberger D, Kunze S, Muller U (1999) Molecular diagnosis of bilateral coronal synostosis. Plast Reconstr Surg 104:1603–1615
Reardon W, Wilkes D, Rutland P, Pulleyn LJ, Malcolm S, Dean JCS, Evans RD, Jones BM, Hayward R, Hall CM, Nevin NC, Baraitser M, Winter RM (1997) Craniosynostosis associated with FGFR3 pro250-to-arg mutation results in a range of clinical presentations including unisutural sporadic craniosynostosis. J Med Genet 34:632–636
Robin NH, Scott JA, Cohen AR, Goldstein JA (1998) Nonpenetrance in FGFR3-associated coronal synostosis syndrome. Am J Med Genet 80:296–297
Shiang R, Thompson LM, Zhu YZ, Church DM, Fielder TJ, Bocian M, Winokur ST, Wasmuth JJ (1994) Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. Cell 78:335–342
Shuper A, Merlob P, Grunebaum M, Reisner SH (1985) The incidence of isolated craniosynostosis in the newborn infant. Am J Dis Child 139:85–86
Tavormina PL, Shiang R, Thompson LM, Zhu YZ, Wilkin DJ, Lachman RS, Wilcox WR, Rimoin DL, Cohn DH, Wasmuth JJ (1995) Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3. Nat Genet 9:321–328
Trusen A, Beissert M, Collmann H, Darge K (2003) The pattern of skeletal anomalies in the cervical spine, hands and feet in patients with Saethre-Chotzen syndrome and Muenke-type mutation. Pediatr Radiol 33:168–172
Tsai FJ, Wu JY, Lee CC, Tsa CH (2000) A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) causes non-syndromic craniosynostosis. Acta Paediatr 89:672–674
Vajo Z, Francomano CA, Wilkin DJ (2000) The molecular and genetic basis of fibroblast growth factor receptor 3 disorders: the achondroplasia family of skeletal dysplasias, Muenke craniosynostosis, and Crouzon syndrome with acanthosis nigricans. Endocr Rev 21:23–39
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Sabatino, G., Di Rocco, F., Zampino, G. et al. Muenke syndrome. Childs Nerv Syst 20, 297–301 (2004). https://doi.org/10.1007/s00381-003-0906-y
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DOI: https://doi.org/10.1007/s00381-003-0906-y