Abstract
The post eighteen months have been exciting time for craniosynostosis research. In a rapid flurry of publications, mutations of fibroblast growth factor receptors (FGFRs) have been identified in three of the best known craniosynostosis syndromes, namely Apert, Crouzon and Pfeiffer syndromes, as well as in Jackson-Weiss syndrome and thanatophoric dysplasia. These findings open many new avenues for craniosynostosis research including studies of diagnosis, pathogenesis, and mutagenesis. Here the major findings and their implications have been briefly reviewed.
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References
Cohen MM Jr. Syndromes with craniosynostosis. In: Cohen MM Jr., ed.Craniosynostosis: Diagnosis, Evaluation and Management, New York: Raven Press, 1986; 413–590.
Hunter AGW, Rudd NL. Craniosynostosis. I. Sagittal synostosis; its genetics and associated clinical findings in 214 patients who lacked involvement of the coronal suture (s).Teratology 1976; 14: 185–194.
Lajeunie E, Le Merrer M, Bonaiti-Pellie C, Marchac D, Renier D. Genetic study of nonsyndromic coronal craniosynostosis.Am J Med Genet 1995; 55: 500–504.
Gorlin RJ, Cohen MM Jr., Levin LS. Syndromes with craniosynostosis: general aspects and well-known syndromes. In:Syndromes of the Head and Neck, New York: Oxford University Press, 1990; 519–539.
Jackson CE, Weiss L, Reynolds WA, Forman TF, Peterson JA. Craniosynostosis, midfacial hypoplasia, and foot abnormalities: an autosomal dominant phenotype in a large Amish kindred.J Pediatr 1976; 88: 963–968.
Preston RA, Post JC, Keats BJBet al. A gene for Crouzon craniofacial dysostosis maps to the long arm of chromosome 10.Nature Genet 1994; 7: 149–153.
Li X, Lewanda AF, Eluma Fet al. Two craniosynostotic syndrome loci, Crouzon and Jackson-Weiss, map to chromosome 10q23–q26.Genomics 1994; 22: 418–424.
Robin NH, Feldman GJ, Mitchell HFet al. Linkage of Pfeiffer syndrome to chromosome 8 centromere and evidence for genetic heterogeneity.Hum Mol Genet 1994; 3: 2153–2158.
Shiang R, Thompson LM, Zhu Y-Zet al. Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, Achondroplasia.Cell 1994; 78: 335–342.
Rousseau F, Bonaventure J, Legeal-Mallet Let al. Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia.Nature 1994; 371: 252–254.
Ballabio A. The rise and fall of positional cloning?Nature Genet 1993; 3: 277–279.
Reardon W, Winter RM, Rutland Pet al. Mutations in the fibroblast growth factor receptor 2 gene cause Crouzon syndrome.Nature Genet 1994; 8: 98–103.
Muenke M, Schell U, Hehr Aet al. A common mutation in the fibroblast growth factor receptor 1 gene in Pfeiffer syndrome.Nature Genet 1994; 8: 269–274.
Jabs EW, Li X, Scott AFet al. Jackson-Weiss and Crouzon syndromes are allelic with mutations in fibroblast growth factor receptor 2.Nature Genet 1994; 8: 275–279.
Wilkie AOM, Slaney SF, Oldridge Met al. Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndrome.Nature Genet 1995; 9: 165–172.
Tavormina PL, Shiang R, Thompson LMet al. Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3.Nature Genet 1995; 9: 321–328.
Rutland P, Pulleyn LJ, Reardon Wet al. Identical mutations in the FGFR2 gene cause both Pfeiffer and Crouzon syndrome phenotypes.Nature Genet 1995; 9: 173.
Lajeunie E, Ma HW, Bonaventure Jet al. FGFR2 mutations in Pfeiffer syndrome.Nature Genet 1995; 9: 108.
Schell U, Hehr A, Feldman GJet al. Mutations in FGFR1 and FGFR2 cause familial and sporadic Pfeiffer syndrome.Hum Mol Genet 1995; 4: 323–328.
Meyers GA, Orlow SJ, Munro IRet al. FGFR3 mutations in Crouzon syndrome with acanthosis nigricans.Nature Genet 1995; 9: 462–464.
Gorry MC, Preston RA, White GJet al. Crouzon syndrome: mutations in two spliceoforms of FGFR2 and a common point mutation shared with Jackson-Weiss syndrome.Hum Mol Genet 1995; 4: 1387–1390.
Park W-J, Meyers GA, Li Xet al. Novel FGFR2 mutations in Crouzon and Jackson-Weiss syndromes show allelic heterogeneity and phenotypic variability.Hum Mol Genet 1995; 4: 1229–1233.
Park W-J, Theda C, Maestri NEet al. Analysis of phenotypic features and FGFR2 mutations in Apert syndrome.Am J Hum Genet 1995; 57: 321–328.
Slaney SF, Oldridge M, Hurst JAet al. Differential effects of FGFR2 mutations on syndactyly and cleft palate in Apert syndrome.Am J Hum Genet 1996; 58: 923–932.
Oldridge M, Wilkie AOM, Slaney SFet al. Mutations in the third immunoglobulin domain of the fibroblast growth factor receptor-2 gene in Crouzon syndrome.Hum Mol Genet 1995; 4: 1077–1082.
Steinberger D, Mulliken JB, Muller U. Predisposition for cysteine substitutions in the immunoglobulin-like chain of FGFR2 in Crouzon syndrome.Hum Genet 1995; 96: 113–115.
Rousseau F, Saugier P, Le Merrer Met al. Stop codon FGFR3 mutations in thanatophoric dwarfism type 1.Nature Genet 1995; 10: 11–12.
Tavormina PL, Rimoin DL, Cohn DHet al. Another mutation that results in the substitution of an unpaired cysteine residue in the extracellular domain of FGFR3 in thanatophoric dysplasia type 1.Hum Mol Genet 1995; 4: 2175–2177.
Johnson DE, Williams LT. Structural and functional diversity in the FGF receptor multigene family. In: Vande Woude GF, Klein G, (eds).Advances in Cancer Research, Vol. 60, San Diego: Academic Press, Inc., 1993; 1–41.
Mason IJ. The ins and outs of fibroblast growth factors.Cell 1994; 78: 547–552.
Orr-Urtreger A, Bedford MT, Burakova Tet al. Developmental localization of the splicing alternatives of fibroblast growth factor receptor-2 (FGFR2).Dev Biol 1993; 158: 475–486.
Wilkie AOM, Morriss-Kay GM, Jones EY, Heath JK. Functions of fibroblast growth factors and their receptors.Curr Biol 1995; 5: 500–507.
Wilkie AOM. The molecular basis of genetic dominance.J Med Genet 1994; 31: 89–98.
Rose CSP, King AAJ, Summers Det al. Localization of the genetic locus for Saethre-Chotzen syndrome to a 6 cM region of chromosome 7 using four cases with apparently balanced translocations at 7p21.2.Hum Mol Genet 1994; 3: 1405–1408.
Lewanda AF, Green ED, Weissenbach Jet al. Evidence that the Saethre-Chotzen syndrome locus lies between D7S664 and D7S507, by genetic analysis and detection of a microdeletion in a patient.Am J Hum Genet 1994; 55: 1195–1201.
Tsuji K, Narahara K, Yokoyama Y, Grzeschik K-H, Kunz J. The breakpoint on 7p in a patient with t(6; 7) and craniosynostosis is spanned by a YAC clone containing the D7S503 locus.Hum Genet 1995; 95: 303–307.
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Wilkie, A.O.M. Fibroblast growth factor receptor mutations and craniosynostosis: Three receptors, five syndromes. Indian J Pediatr 63, 351–356 (1996). https://doi.org/10.1007/BF02751527
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DOI: https://doi.org/10.1007/BF02751527