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AIMS Genetics

2016, Volume 3, Issue 1: 99-129. doi: 10.3934/genet.2016.1.99
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Review Topical Sections

Craniosynostosis: current conceptions and misconceptions

  • 1.
    Finnell Birth Defects Research Laboratory, Dell Pediatric Research Institute, The University of Texas at Austin, USA
  • 2.
    Department of Nutritional Sciences, Dell Pediatric Research Institute, The University of Texas at Austin, USA
  • 3.
    Pediatric Neurosurgery, Dell Children’s Medical Center, Professor, Department of Surgery, Dell Medical School, Austin, TX, USA
  • 4.
    Plastic Surgery, Craniofacial Team at the Dell Children’s Medical Center of Central Texas, Austin, USA
  • Received: 17 February 2016 Accepted: 12 April 2016 Published: 14 April 2016

  • Cranial bones articulate in areas called sutures that must remain patent until skull growth is complete. Craniosynostosis is the condition that results from premature closure of one or more of the cranial vault sutures, generating facial deformities and more importantly, skull growth restrictions with the ability to severely affect brain growth. Typically, craniosynostosis can be expressed as an isolated event, or as part of syndromic phenotypes. Multiple signaling mechanisms interact during developmental stages to ensure proper and timely suture fusion. Clinical outcome is often a product of craniosynostosis subtypes, number of affected sutures and timing of premature suture fusion. The present work aimed to review the different aspects involved in the establishment of craniosynostosis, providing a close view of the cellular, molecular and genetic background of these malformations.

    Citation: Cristiane Sá Roriz Fonteles, Richard H. Finnell, Timothy M. George, Raymond J. Harshbarger. Craniosynostosis: current conceptions and misconceptions[J]. AIMS Genetics, 2016, 3(1): 99-129. doi: 10.3934/genet.2016.1.99

    Related Papers:

  • Cranial bones articulate in areas called sutures that must remain patent until skull growth is complete. Craniosynostosis is the condition that results from premature closure of one or more of the cranial vault sutures, generating facial deformities and more importantly, skull growth restrictions with the ability to severely affect brain growth. Typically, craniosynostosis can be expressed as an isolated event, or as part of syndromic phenotypes. Multiple signaling mechanisms interact during developmental stages to ensure proper and timely suture fusion. Clinical outcome is often a product of craniosynostosis subtypes, number of affected sutures and timing of premature suture fusion. The present work aimed to review the different aspects involved in the establishment of craniosynostosis, providing a close view of the cellular, molecular and genetic background of these malformations.


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    [1] Slater BJ, Lenton KA, Kwan MD, et al. (2008) Cranial sutures: a brief review. Plast Reconstr Surg 121: 170e-178e. doi: 10.1097/01.prs.0000304441.99483.97
    [2] Twigg SR, Wilkie AO (2015) A genetic-pathophysiological framework for craniosynostosis. Am J Hum Genet 97: 359-377. doi: 10.1016/j.ajhg.2015.07.006
    [3] Hamm JA, Robin NH (2015) Newborn craniofacial malformations. Orofacial clefting and craniosynostosis. Clin Perinotol 42: 321-336.
    [4] Persing JA, Jane JA, Shaffrey M (1989) Virchow and the pathogenesis of craniosynostosis: a translation of his work. Plast Reconstr Surg 83: 738-742. doi: 10.1097/00006534-198904000-00025
    [5] Patel A, Terner J, Travieso R, et al. (2012) On Bernard Sarnat's 100th birthday: pathology and management of craniosynostosis. J Craniofac Surg 23: 105-112. doi: 10.1097/SCS.0b013e318240fb0d
    [6] Cohen MM Jr (2005) Editorial: perspectives on craniosynostosis. Am J Med Genet A 136A: 313-326. doi: 10.1002/ajmg.a.30757
    [7] Boulet SL, Rasmussen SA, Honein MA (2008) A population-based study of craniosynostosis in metropolitan Atlanta, 1989-2003. Am J Med Genet A 146A: 984-991. doi: 10.1002/ajmg.a.32208
    [8] Lee HQ, Hutson JM, Wray AC, et al. (2012) Changing epidemiology of nonsyndromic craniosynostosis and revisiting the risk factors. J Craniofac Surg 23: 1245-1251. doi: 10.1097/SCS.0b013e318252d893
    [9] Chim H, Manjila S, Cohen AR, et al. (2011) Molecular signaling in pathogenesis of craniosynostosis: the role of fibroblast growth factor and transforming growth factor-b. Neurosurg Focus 31: E7.
    [10] Kabbani H, Raghuveer TS (2004) Craniosynostosis. Am Fam Physician 69: 2863-2870.
    [11] Kimonis V, Gold JA, Hoffman TL, et al. (2007) Genetics of craniosynostosis. Semin Pediatr Neurol 14: 150-161. doi: 10.1016/j.spen.2007.08.008
    [12] French LR, Jackson IT, Melton LJ (1990) A population-based study of craniosynostosis. J Clin Epidemiol 43: 69-73. doi: 10.1016/0895-4356(90)90058-W
    [13] Alazami AM, Seidahmed MZ, Alzahrani F, et al. (2014) Novel IFT122 mutation associated with impaired ciliogenesis and cranioectodermal dysplasia. Mol Genet Genomic Med 2: 103-106. doi: 10.1002/mgg3.44
    [14] Currarino G (2007) Sagittal synostosis in X-linked hypophosphatemic rickets and related diseases. Pediatr Radiol 37: 805-812. doi: 10.1007/s00247-007-0503-4
    [15] Adès LC, Sullivan K, Biggin A, et al. (2006) FBN1, TGFBR1, and the Marfan-craniosynostosis/mental retardation disorders revisited. Am J Med Genet A 140: 1047-1058.
    [16] Iqbal Z, Cejudo-Martin P, de Brouwer A, et al. (2010) Disruption of the podosome adaptor protein TKS4 (SH3PXD2B) causes the skeletal dysplasia, eye, and cardiac abnormalities of Frank-Ter Haar Syndrome. Am J Hum Genet 86: 254-261. doi: 10.1016/j.ajhg.2010.01.009
    [17] Agrawal D, Steinbok P, Cochrane DD (2006) Diagnosis of isolated sagittal synostosis: are radiographic studies necessary? Childs Nerv Syst 22: 375-378. doi: 10.1007/s00381-005-1243-0
    [18] Levi B, Wan DC, Wong VW, et al. (2012) Cranial suture biology: from pathways to patient care. J Craniofac Surg 23: 13-19. doi: 10.1097/SCS.0b013e318240c6c0
    [19] Van der Meulen J (2012) Metopic synostosis. Childs Nerv Syst 28: 1359-1367. doi: 10.1007/s00381-012-1803-z
    [20] Yee ST, Fearon JA, Gosain AK, et al. (2015) Classification and Management of Metopic Craniosynostosis. J Craniofac Surg 26: 1812-1817. doi: 10.1097/SCS.0000000000001866
    [21] Senarath-Yapa K, Chung MT, McArdle A, et al. (2012) Craniosynostosis: molecular pathways and future pharmacologic therapy. Organogenesis 8: 103-113. doi: 10.4161/org.23307
    [22] Jehee FS, Johnson D, Alonso LG, et al. (2005) Molecular screening for microdeletions at 9p22-p24 and 11q23-q24 in a large cohort of patients with trigonocephaly. Clin Genet 67: 503-510. doi: 10.1111/j.1399-0004.2005.00438.x
    [23] Hoischen A, van Bon BW, Rodriguez-Santiago B, et al. (2011) De novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome. Nat Genet43: 729-731.
    [24] Malpuech G, Demeocq F, Palcoux JB, et al. (1983) A previously undescribed autosomal recessive multiple congenital anomalies/mental retardation (MCA/MR) syndrome with growth failure, lip/palate cleft(s), and urogenital anomalies. Am J Med Genet 16: 475-480. doi: 10.1002/ajmg.1320160405
    [25] Vissers LE, Cox TC, Maga AM, et al. (2011) Heterozygous mutations of FREM1 are associated with an increased risk of isolated metopic craniosynostosis in humans and mice. PLoS Genet 7: e1002278. doi: 10.1371/journal.pgen.1002278
    [26] McDonald-McGinn DM, Feret H, Nah HD, et al. (2010) Metopic craniosynostosis due to mutations in GLI3: A novel association. Am J Med GenetA 152A: 1654-1660.
    [27] Twigg SR, Lloyd D, Jenkins D, et al. (2012) Mutations in multidomain protein MEGF8 identify a Carpenter syndrome subtype associated with defective lateralization. Am J Hum Genet91: 897-905.
    [28] Wilkie AO, Byren JC, Hurst JA, et al. (2010) Prevalence and complications of single-gene and chromosomal disorders in craniosynostosis. Pediatrics 126: e391-400. doi: 10.1542/peds.2009-3491
    [29] Lajeunie E, Le Merrer M, Bonaïti-Pellie C, et al. (1995) Genetic study of nonsyndromic coronal craniosynostosis. Am J Med Genet 55: 500-504. doi: 10.1002/ajmg.1320550422
    [30] Ziyadeh J, Le Merrer M, Robert M, et al. (2013) Mucopolysaccharidosis type I and craniosynostosis. Acta Neurochir (Wien) 155: 1973-1976. doi: 10.1007/s00701-013-1831-9
    [31] Villarreal DD, Villarreal H, Paez AM, et al. (2013) A patient with a unique frameshift mutation in GPC3, causing Simpson-Golabi-Behmel syndrome, presenting with craniosynostosis, penoscrotal hypospadias, and a large prostatic utricle. Am J Med Genet A 161A: 3121-3125.
    [32] Shahinian HK, Jaekle R, Suh RH, et al. (1998) Obstetrical factors governing the etiopathogenesis of lambdoid synostosis. Am J Perinatol 15: 281-286. doi: 10.1055/s-2007-993943
    [33] Czerwinski M, Kolar JC, Fearon JA (2011) Complex craniosynostosis. Plast Reconstr Surg 128: 955-961. doi: 10.1097/PRS.0b013e3182268ca6
    [34] Chai Y, Maxson RE Jr (2006) Recent advances in craniofacial morphogenesis. Dev Dyn 235: 2353-2375. doi: 10.1002/dvdy.20833
    [35] Schweizer G, Ayer-LeLièvre C, Le Douarin NM (1983) Restrictions in developmental capacities in the dorsal root ganglia during the course of development. Cell Differ 13:191-200. doi: 10.1016/0045-6039(83)90089-1
    [36] Spears R, Svoboda KKH (2005) Growth factors and signaling proteins in craniofacial development. Semin Orthod 11: 184-198. doi: 10.1053/j.sodo.2005.07.003
    [37] Delannet M, Duband JL (1992) Transforming growth factor-beta control of cell-substratum adhesion during avian neural crest cell emigration in vitro. Development 116: 275-287.
    [38] Baird A (1994) Fibroblast growth factors: activities and significance of nonneurotrophin neurotrophic growth factors. Curr Opin Neurobiol 4: 78-86. doi: 10.1016/0959-4388(94)90035-3
    [39] Morrison-Graham K, Schatteman GC, Bork T, et al. (1992) A PDGF receptor mutation in the mouse (Patch) perturbs the development of a non-neuronal subset of neural crest-derived cells. Development 115: 133-142.
    [40] Bodine PV (2008) Wnt signalling controlo f bone cell apoptosis. Cell Res 18: 248-253. doi: 10.1038/cr.2008.13
    [41] Noden DM (1983) The role of the neural crest in patterning of avian cranial skeletal, connective, and muscle tissues. Dev Biol 96: 144-165. doi: 10.1016/0012-1606(83)90318-4
    [42] Deckelbaum RA, Holmes G, Zhao Z, et al. (2012) Regulation of cranial morphogenesis and cell fate at the neural crest-mesoderm boundary by engrailed 1. Development 139: 1346-1358. doi: 10.1242/dev.076729
    [43] Twigg SR, Kan R, Babbs C, et al. (2004) Mutations of ephrin-B1 (EFNB1), a marker of tissue boundary formation, cause craniofrontonasal syndrome. Proc Natl Acad Sci U S A 101: 8652 - 8657. doi: 10.1073/pnas.0402819101
    [44] Merrill AE, Bochukova EG, Brugger SM, et al. (2006) Cell mixing at a neural crest-mesoderm boundary and deficient ephrin-Eph signaling in the pathogenesis of craniosynostosis. Hum Mol Genet 15: 1319-1328. doi: 10.1093/hmg/ddl052
    [45] Noden DM (1978) The control of avian cephalic neural crest cytodifferentiation. I. Skeletal and connective tissues. Dev Biol 67: 296-312.
    [46] Noden DM (1988) Interactions and fates of avian craniofacial mesenchyme. Development 103: 121-140.
    [47] Le Lievre CS (1978) Participation of neural crest-derived cells in the genesis of the skull in birds. J Embryol Exp Morphol 47: 17-37.
    [48] Couly GF, Coltey PM, Le Douarin NM (1993) The triple origin of skull in higher vertebrates: a study in quail-chick chimeras. Development 117: 409-429.
    [49] Jiang X, Iseki S, Maxson RE, et al. (2002) Tissue origins and interactions in the mammalian skull vault. Dev Biol 241: 106-116. doi: 10.1006/dbio.2001.0487
    [50] Nie X (2005) Cranial base in craniofacial development: developmental features, influence on facial growth, anomaly, and molecular basis. Acta Odontol Scand 63:127-135. doi: 10.1080/00016350510019847
    [51] Sasaki T, Ito Y, Bringas P Jr, et al. (2006) TGF (beta)-mediated FGF signaling is crucial for regulating cranial neural crest cell proliferation during frontal bone development. Development 133: 371-381.
    [52] Bernard S, Loukas M, Rizk E, et al. (2015) The human occipital bone: review and update on its embryology and molecular development. Childs Nerv Syst 31: 2217-2223. doi: 10.1007/s00381-015-2870-8
    [53] Mishina Y, Snider TN (2014) Neural crest cell signaling pathways critical to cranial bone development and pathology. Exp Cell Res 325: 138-147. doi: 10.1016/j.yexcr.2014.01.019
    [54] Zhao H, Feng J, Ho TV, et al. (2015) The suture provides a niche for mesenchymal stem cells of craniofacial bones. Nat Cell Biol 17: 386-396. doi: 10.1038/ncb3139
    [55] Ogle RC, Tholpady SS, McGlynn KA, et al. (2004) Regulation of cranial suture morphogenesis. Cells Tissues Organs 176: 54-66. doi: 10.1159/000075027
    [56] Opperman LA, Rawlins JT (2005) The extracellular matrix environment in suture morphogenesis and growth. Cells Tissues Organs 181: 127-135. doi: 10.1159/000091374
    [57] Manzanares MC, Goret-Nicaise M, Dhem A (1988) Metopic sutural closure in the human skull. J Anat 161: 203-215.
    [58] Sahar DE, Longaker MT, Quarto N (2005) Sox9 neural crest determinant gene controls patterning and closure of the posterior frontal cranial suture. Dev Biol 280: 344-361. doi: 10.1016/j.ydbio.2005.01.022
    [59] Opperman LA (2000) Cranial sutures as intramembranous bone growth sites. Dev Dyn 219: 472-485.
    [60] Gagan JR, Tholpady SS, Ogle RC (2007) Cellular dynamics and tissue interactions of the dura mater during head development. Birth Defects Res C Embryo Today 81: 297-304. doi: 10.1002/bdrc.20104
    [61] Richtsmeier JT, Flaherty K (2013) Hand in glove: brain and skull in development and dysmorphogenesis. Acta Neuropathol 125: 469-489. doi: 10.1007/s00401-013-1104-y
    [62] Mao JJ, Nah HD (2004) Growth and development: hereditary and mechanical modulations. Am J Orthod Dentofacial Orthop 125: 676-689. doi: 10.1016/j.ajodo.2003.08.024
    [63] Todd TW, Lyon DW (1925) Cranial suture closure: Its progress and age relationship. Part II. Ectocranial closure in adult males of white stock. Am J Phys Anthropol 8: 23-45.
    [64] Ting MC, Wu NL, Roybal PG, et al. (2009) EphA4 as an effector of Twist1 in the guidance of osteogenic precursor cells during calvarial bone growth and in craniosynostosis. Development 136: 855-864.
    [65] Greenwald JA, Mehrara BJ, Spector JA, et al. (2000) Regional differentiation of cranial suture-associated dura mater in vivo and in vitro: implications for suture fusion and patency. J Bone Miner Res 15: 2413-2430. doi: 10.1359/jbmr.2000.15.12.2413
    [66] Zimmerman B, Moegelin A, de Souza P, et al. (1998) Morphology of the development of the sagittal suture of mice. Anat Embryol (Berl) 197:155-165. doi: 10.1007/s004290050127
    [67] Senarath-Yapa K, Li S, Meyer NP, et al. (2013) Integration of multiple signaling pathways determines differences in the osteogenic potential and tissue regeneration of neural crest-derived and mesoderm-derived calvarial bones. Int J Mol Sci 14: 5978-5997.
    [68] Quarto N, Wan DC, Kwan MD, et al. (2010) Origin matters: differences in embryonic tissue origin and Wnt signaling determine the osteogenic potential and healing capacity of frontal and parietal calvarial bones. J Bone Miner Res 25: 1680-1694.
    [69] Cohen Jr MM (1993) Sutural biology and the correlates of craniosynostosis. Am J Med Genet 47: 581-616.
    [70] Pritchard JJ, Scott JH, Girgis FG (1956) The structure and development of cranial and facial sutures. J Anat 90: 73 - 86.
    [71] Koskinen-Moffett LK, Moffett BC Jr, Graham JM Jr (1982) Cranial synostosis and intra-uterine compression: a developmental study of human sutures. Prog Clin Biol Res 101: 365-378.
    [72] Kokich VG (1976) Age changes in the human frontozygomatic suture from 20 to 95 years. Am J Orthod 69: 411-430. doi: 10.1016/0002-9416(76)90209-8
    [73] Morriss-Kay GM, Wilkie AO (2005) Growth of the normal skull vault and its alteration in craniosynostosis: insights from human genetics and experimental studies. J Anat 207: 637-653. doi: 10.1111/j.1469-7580.2005.00475.x
    [74] Nayak SR, Krishnamurthy A, Kumar SJM, et al. (2007) The mendosal suture of the occipital bone: occurrence in Indian population, embryology and clinical significance. Surg Radiol Anat 29: 329-332. doi: 10.1007/s00276-007-0216-2
    [75] Kirmi O, Lo SJ, Johnson D, et al. (2009) Craniosynostosis: a radiological and surgical perspective. Semin Ultrasound CT MR 30: 492-512. doi: 10.1053/j.sult.2009.08.002
    [76] Vu HL, Panchal J, Parker EE, et al. (2001) The timing of physiologic closure of the metopic suture: a review of 159 patients using reconstructed 3D CT scans of the craniofacial region. J Craniofac Surg 12: 527-532. doi: 10.1097/00001665-200111000-00005
    [77] Park SS, Beyer RP, Smyth MD, et al. (2015) Osteoblast differentiation profiles define sex specific gene expression patterns in craniosynostosis. Bone 76: 169-176. doi: 10.1016/j.bone.2015.03.001
    [78] Kim HJ, Rice DP, Kettunen PJ, et al. (1998) FGF-, BMP- and Shh-mediated signalling pathways in the regulation of cranial suture morphogenesis and calvarial bone development. Development 125: 1241-1251.
    [79] Mansukhani A, Ambrosetti D, Holmes G, et al. (2005) Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation. J Cell Biol 168: 1065-1076. doi: 10.1083/jcb.200409182
    [80] Liu B, Yu HM, Hsu W (2007) Craniosynostosis caused by Axin2 deficiency is mediated through distinct functions of beta-catenin in proliferation and differentiation. Dev Biol 301: 298-308. doi: 10.1016/j.ydbio.2006.10.018
    [81] McMahon JA, Takada S, Zimmerman LB, et al. (1998) Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite. Genes Dev 12: 1438-1452. doi: 10.1101/gad.12.10.1438
    [82] Rosen V (2006) BMP and BMP inhibitors in bone. Ann N Y Acad Sci 1068: 19-25. doi: 10.1196/annals.1346.005
    [83] Warren SM, Brunet LJ, Harland RM, et al. (2003) The BMP antagonist noggin regulates cranial suture fusion. Nature 422: 625-629. doi: 10.1038/nature01545
    [84] Rice DP, Kim HJ, Thesleff I (1999) Apoptosis in murine calvarial bone and suture development. Eur J Oral Sci 107: 265-275. doi: 10.1046/j.0909-8836.1999.eos107406.x
    [85] Agresti M, Gosain AK (2005) Detection of apoptosis in fusing versus nonfusing mouse cranial sutures. J Craniofac Surg 16: 572-578. doi: 10.1097/01.scs.0000168759.61947.7f
    [86] Opperman LA, Sweeney TM, Redmon J, et al. (1993) Tissue interactions with underlying dura mater inhibit osseous obliteration of developing cranial sutures. Dev Dyn 198: 312-322. doi: 10.1002/aja.1001980408
    [87] Opperman LA, Passarelli RW, Morgan EP, et al. (1995) Cranial sutures require tissue interactions with dura mater to resist osseous obliteration in vitro. J Bone Miner Res 10: 1978-1987.
    [88] Tholpady SS, Freyman TF, Chachra D, et al. (2007) Tensional forces influence gene expression and sutural state of rat calvariae in vitro. Plast Reconstr Surg 120: 601-611. doi: 10.1097/01.prs.0000270284.69632.6b
    [89] Mao JJ (2002) Mechanobiology of craniofacial sutures. J Dent Res 81: 810-816. doi: 10.1177/154405910208101203
    [90] Kopher RA, Mao JJ (2003) Suture growth modulated by the oscillatory component of micromechanical strain. J Bone Min Res 18: 521-528. doi: 10.1359/jbmr.2003.18.3.521
    [91] Mao JJ, Wang X, Kopher RA, et al. (2003) Strain induced osteogenesis in the cranial suture upon controlled delivery of low-frequency cyclic forces. Front Biosci 8: A10-A17. doi: 10.2741/917
    [92] Ingber DE, Tensegrity I (2003) Cell structure and hierarchical systems biology. J Cell Sci 116: 1157-1173. doi: 10.1242/jcs.00359
    [93] Carinci P, Becchetti E, Bodo M (2000) Role of the extracellular matrix and growth factors in skull morphogenesis and in the pathogenesis of craniosynostosis. Int J Dev Biol 44: 715-723.
    [94] Salmivirta M, Jalkanen M (1995) Syndecan family of cell surface proteoglycans: developmentally regulated receptors for extracellular effector molecules. Experientia 51: 863-872. doi: 10.1007/BF01921737
    [95] Bidwell JP, Pavalko FM (2010) The Load-Bearing Mechanosome Revisited. Clin Rev Bone Miner Metab 8: 213-223. doi: 10.1007/s12018-010-9075-1
    [96] Carinci P, Becchetti E, Baroni T, et al. (2007) Extracellular matrix and growth factors in the pathogenesis of some craniofacial malformations. Eur J Histochem 51: 105-116.
    [97] Bodo M, Carinci F, Baroni T, et al. (1997) Apert's syndrome: differential in vitro production of matrix macromolecules and its regulation by interleukins. Eur J Clin Invest 27: 36-42.
    [98] Bodo M, Carinci F, Baroni T, et al. (1998) Interleukin pattern of Apert fibroblasts in vitro. Eur J Cell Biol 75: 383-388. doi: 10.1016/S0171-9335(98)80072-1
    [99] Locci P, Baroni T, Pezzetti F, et al. (1999) Differential in vitro phenotype pattern, transforming growth factorbeta(1) activity and mRNA expression of transforming growth factor-beta(1) in Apert osteoblasts. Cell Tissue Res 297: 475-483. doi: 10.1007/s004410051374
    [100] Bodo M, Baroni T, Carinci F, et al. (1999) A regulatory role of fibroblast growth factor in the expression of decorin, biglycan, betaglycan and syndecan in osteoblasts from patients with Crouzon's syndrome. Eur J Cell Biol 78: 323-330. doi: 10.1016/S0171-9335(99)80066-1
    [101] Su N, Jin M, Chen L (2014) Role of FGF/FGFR signaling in skeletal development and homeostasis: learning from mouse models. Bone Res 2: 14003. doi: 10.1038/boneres.2014.3
    [102] Liu YH, Tang Z, Kundu RK, et al. (1999) Msx2 gene dosage influences the number of proliferative osteogenic cells in growth centers of the developing murine skull: a possible mechanism for MSX2-mediated craniosynostosis in humans. Dev Biol 205: 260-274. doi: 10.1006/dbio.1998.9114
    [103] Cohen MM Jr (1997) Transforming growth factor beta s and fibroblast growth factors and their receptors: role in sutural biology and craniosynostosis. J Bone Miner Res 12: 322-331. doi: 10.1359/jbmr.1997.12.3.322
    [104] Jabs EW, Müller U, Li X, et al. (1993) A mutation in the homeodomain of the human MSX2 gene in a family affected with autosomal dominant craniosynostosis. Cell 75: 443-450. doi: 10.1016/0092-8674(93)90379-5
    [105] Warman ML, Mulliken JB, Hayward PG, et al. (1993) Newly recognized autosomal dominant craniosynostotic syndrome. Am J Med Genet 46: 444-449. doi: 10.1002/ajmg.1320460420
    [106] Ma L, Golden S, Wu L, et al. (1996) The molecular basis of Boston-type craniosynostosis: the Pro148-->His mutation in the N-terminal arm of the MSX2 homeodomain stabilizes DNA binding without altering nucleotide sequence preferences. Hum Mol Genet 5: 1915-1920. doi: 10.1093/hmg/5.12.1915
    [107] Wilkie AO, Tang Z, Elanko N, et al. (2000) Functional haploinsufficiency of the human homeobox gene MSX2 causes defects in skull ossification. Nat Genet 24: 387-390.
    [108] Alappat S, Zhang ZY, Chen YP (2003) Msx homeobox gene family and craniofacial development. Cell Res 13: 429-442. doi: 10.1038/sj.cr.7290185
    [109] MacKenzie A, Ferguson MW, Sharpe PT (1992) Expression patterns of the homeobox gene, Hox-8, in the mouse embryo suggest a role in specifying tooth initiation and shape. Development 115: 403-420.
    [110] Jowett AK, Vainio S, Ferguson MW, et al. (1993) Epithelial-mesenchymal interactions are required for msx 1 and msx 2 gene expression in the developing murine molar tooth. Development 117: 461-470.
    [111] Catron KM, Wang H, Hu G, et al. (1996) Comparison of MSX-1 and MSX-2 suggests a molecular basis for functional redundancy. Mech Dev 55: 185-199. doi: 10.1016/0925-4773(96)00503-5
    [112] Zhang H, Catron KM, Abate-Shen C (1996) A role for the Msx-1 homeodomain in transcriptional regulation: residues in the N-terminal arm mediate TATA binding protein interaction and transcriptional repression. Proc Natl Acad Sci U S A 93: 1764-1769. doi: 10.1073/pnas.93.5.1764
    [113] Newberry EP, Latifi T, Battaile JT, et al. (1997) Structure-function analysis of Msx2-mediated transcriptional suppression. Biochemistry 36: 10451-10462. doi: 10.1021/bi971008x
    [114] Catron KM, Zhang H, Marshall SC, et al. (1995) Transcriptional repression by Msx-1 does not require homeodomain DNA-binding sites. Mol Cell Biol 15: 861-871. doi: 10.1128/MCB.15.2.861
    [115] Wang W, Chen X, Xu H, et al. (1996) Msx3: a novel murine homologue of the Drosophila msh homeobox gene restricted to the dorsal embryonic central nervous system. Mech Dev 58: 203-215. doi: 10.1016/S0925-4773(96)00562-X
    [116] MacKenzie A, Ferguson MW, Sharpe PT (1991) Hox-7 expression during murine craniofacial development. Development 113: 601-611.
    [117] Satokata I, Maas R (1994) Msx1 deficient mice exhibit cleft palate and abnormalities of craniofacial and tooth development. Nat Genet 6: 348-356. doi: 10.1038/ng0494-348
    [118] Turner N, Grose R (2010) Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer 10: 116-129. doi: 10.1038/nrc2780
    [119] Isacchi A, Bergonzoni L, Sarmientos P (1990) Complete sequence of a human receptor for acidic and basic fibroblast growth factors. Nucleic Acids Res 18: 1906. doi: 10.1093/nar/18.7.1906
    [120] Pasquale EB, Singer SJ (1989) Identification of a developmentally regulated protein-tyrosine kinase by using anti-phosphotyrosine antibodies to screen a cDNA expression library. Proc Natl Acad Sci USA 86: 5449-5453. doi: 10.1073/pnas.86.14.5449
    [121] Pasquale EB (1990) A distinctive family of embryonic protein-tyrosine kinase receptors. Proc Natl Acad Sci USA 87: 5812-5816. doi: 10.1073/pnas.87.15.5812
    [122] Partanen J, Makela TP, Eerola E, et al. (1991) FGFR-4, a novel acidic fibroblast growth factor receptor with a distinct expression pattern. EMBO J 10: 1347-1354.
    [123] Wiedemann M, Trueb B (2000) Characterization of a novel protein (FGFRL1) from human cartilage related to FGF receptors. Genomics 69: 275-279. doi: 10.1006/geno.2000.6332
    [124] Sleeman M, Fraser J, McDonald M, et al. (2001) Identification of a new fibroblast growth factor receptor, FGFR5. Gene 271: 171-182. doi: 10.1016/S0378-1119(01)00518-2
    [125] Trueb B (2011) Biology of FGFRL1, the fifth fibroblast growth factor receptor. Cell Mol Life Sci 68: 951-964. doi: 10.1007/s00018-010-0576-3
    [126] Teven CM, Farina EM, Rivas J, et al. (2014) Fibroblast growth factor (FGF) signaling in development and skeletal diseases. Genes Dis 1: 199-213. doi: 10.1016/j.gendis.2014.09.005
    [127] Beenken A, Mohammadi M (2009) The FGF family: biology, pathophysiology and therapy. Nat Rev Drug Discov 8: 235-253. doi: 10.1038/nrd2792
    [128] Green PJ, Walsh FS, Doherty P (1996) Promiscuity of fibroblast growth factor receptors. Bioessays 18: 639-646. doi: 10.1002/bies.950180807
    [129] Iseki S, Wilkie AO, Heath JK, et al. (1997) Fgfr2 and osteopontin domains in the developing skull vault are mutually exclusive and can be altered by locally applied FGF2. Development 124: 3375-3384.
    [130] Delezoide AL, Benoist-Lasselin C, Legeai-Mallet L, et al. (1998) Spatio-temporal expression of FGFR 1, 2 and 3 genes during human embryo-fetal ossification. Mech Dev 77: 19-30. doi: 10.1016/S0925-4773(98)00133-6
    [131] Gosain AK, Recinos RF, Agresti M, et al. (2004) TGF-beta1, FGF-2, and receptor mRNA expression in suture mesenchyme and dura versus underlying brain in fusing and nonfusing mouse cranial sutures. Plast Reconstr Surg 113: 1675-1684. doi: 10.1097/01.PRS.0000117362.33347.43
    [132] Crossley PH, Minowada G, McArthur CA, et al. (1996) Roles for FGF8 in the induction, initiation, and maintenance of chick limb development. Cell 84: 127-136. doi: 10.1016/S0092-8674(00)80999-X
    [133] Sarkar S, Petiot A, Copp A, et al. (2001) FGF2 promotes skeletogenic differentiation of cranial neural crest cells. Development 128: 2143-2152.
    [134] Jabs EW, Li X, Scott AF, et al. (1994) Jackson-Weiss and Crouzon syndromes are allelic with mutations in fibroblast growth factor receptor 2. Nat Genet 8: 275-279. doi: 10.1038/ng1194-275
    [135] Muenke M, Schell U, Hehr A, et al. (1994) A common mutation in the fibroblast growth factor receptor 1 gene in Pfeiffer syndrome. Nat Genet 8: 269-274. doi: 10.1038/ng1194-269
    [136] Reardon W, Winter RM, Rutland P, et al. (1994) Mutations in the fibroblast growth factor receptor 2 gene cause Crouzon syndrome. Nat Genet 8: 98-103. doi: 10.1038/ng0994-98
    [137] Shiang R, Thompson LM, Zhu YZ, et al. (1994) Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. Cell 78: 335-342. doi: 10.1016/0092-8674(94)90302-6
    [138] Iseki S, Wilkie AO, Morriss-Kay GM (1999) Fgfr1 and Fgfr2 have distinct differentiation- and proliferation-related roles in the developing mouse skull vault. Development 126: 5611-5620.
    [139] Kan SH, Elanko N, Johnson D, et al. (2002) Genomic screening of fibroblast growth-factor receptor 2 reveals a wide spectrum of mutations in patients with syndromic craniosynostosis. Am J Hum Genet 70:472-86.
    [140] Anderson J, Burns HD, Enriquez-Harris P, et al. (1998) Apert syndrome mutations in fibroblast growth factor receptor 2 exhibit increased affinity for FGF ligand. Hum Mol Genet 7: 1475-1483. doi: 10.1093/hmg/7.9.1475
    [141] Yu K, Herr AB, Waksman G, et al. (2000) Loss of fibroblast growth factor receptor 2 ligand-binding specificity in Apert syndrome. Proc Natl Acad Sci U S A 97:14536-1441. doi: 10.1073/pnas.97.26.14536
    [142] Neilson KM, Friesel RE (1995) Constitutive activation of fibroblast growth factor receptor-2 by a point mutation associated with Crouzon syndrome. J Biol Chem 270: 26037-26040. doi: 10.1074/jbc.270.44.26037
    [143] Robertson SC, Meyer AN, Hart KC, et al. (1998) Activating mutations in the extracellular domain of the fibroblast growth factor receptor 2 function by disruption of the disulfide bond in the third immunoglobulin-like domain. Proc Natl Acad Sci U S A 95: 4567-4572. doi: 10.1073/pnas.95.8.4567
    [144] Oldridge M, Zackai EH, McDonald-McGinn DM, et al. (1999) De novo alu-element insertions in FGFR2 identify a distinct pathological basis for Apert syndrome. Am J Hum Genet 64: 446-461. doi: 10.1086/302245
    [145] Wilkie AOM, Slaney SF, Oldridge M, et al. (1995) Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndrome. Nat Genet 9: 165-172. doi: 10.1038/ng0295-165
    [146] Przylepa KA, Paznekas W, Zhang M, et al. (1996) Fibroblast growth factor receptor 2 mutations in Beare-Stevenson cutis gyrata syndrome. Nat Genet 13: 492-494. doi: 10.1038/ng0896-492
    [147] Li X, Lewanda AF, Eluma F, et al. (1994) Two craniosynostotic syndrome loci, Crouzon and Jackson-Weiss, map to chromosome 10q23-q26. Genomics 22: 418-424.
    [148] Dionne CA, Modi WS, Crumley G, et al. (1992) BEK, a receptor for multiple members of the fibroblast growth factor (FGF) family, maps to human chromosome 10q25.3→q26. Cytogenet Cell Genet 60: 34-36. doi: 10.1159/000133290
    [149] McGillivray G, Savarirayan R, Cox T C, et al. (2005) Familial scaphocephaly syndrome caused by a novel mutation in the FGFR2 tyrosine kinase domain. J Med Genet 42: 656-662. doi: 10.1136/jmg.2004.027888
    [150] Robin NH, Feldman GJ, Mitchell HF, et al. (1994) Linkage of Pfeiffer syndrome to chromosome 8 centromere and evidence for genetic heterogeneity. Hum Mol Genet 3: 2153-2158. doi: 10.1093/hmg/3.12.2153
    [151] Zhou YX, Xu X, Chen L, et al. (2000) A Pro250Arg substitution in mouse Fgfr1 causes increased expression of Cbfa1 and premature fusion of calvarial sutures. Hum Mol Genet 9: 2001-2008. doi: 10.1093/hmg/9.13.2001
    [152] Schell U, Hehr A, Feldman GJ, et al. (1995) Mutations in FGFR1 and FGFR2 cause familial and sporadic Pfeiffer syndrome. Hum Mol Genet 4: 323-328.
    [153] Lajeunie E, Ma HW, Bonaventure J, et al. (1995) FGFR2 mutations in Pfeiffer syndrome. Nat Genet 9: 108. doi: 10.1038/ng0295-108
    [154] Rutland P, Pulleyn LJ, Reardon W, et al. (1995) Identical mutations in the FGFR2 gene cause both Pfeiffer and Crouzon syndrome phenotypes. Nat Genet 9: 173-176. doi: 10.1038/ng0295-173
    [155] Cunningham ML, Seto ML, Ratisoontorn C, et al. (2007) Syndromic craniosynostosis: from history to hydrogen bonds. Orthod Craniofacial Res 10: 67-81. doi: 10.1111/j.1601-6343.2007.00389.x
    [156] Merrill AE, Sarukhanov A, Krejci P, et al. (2012) Bent bone dysplasia-FGFR2 type, a distinct skeletal disorder, has deficient canonical FGF signaling. Am J Hum Genet 90: 550-557. doi: 10.1016/j.ajhg.2012.02.005
    [157] White KE, Cabral JM, Davis SI, et al. (2005) Mutations that cause osteoglophonic dysplasia define novel roles for FGFR1 in bone elongation. Am J Hum Genet 76: 361-367. doi: 10.1086/427956
    [158] Farrow EG, Davis SI, Mooney SD, et al. (2006) Extended mutational analyses of FGFR1 in osteoglophonic dysplasia. Am J Med Genet A 140: 537-539.
    [159] Ibrahimi OA, Zhang F, Eliseenkova AV, et al. (2004) Proline to arginine mutations in FGF receptors 1 and 3 result in Pfeiffer and Muenke craniosynostosis syndromes through enhancement of FGF binding affinity. Hum Mol Genet 13: 69-78.
    [160] Cunningham ML, Seto ML, Ratisoontorn C, et al. (2007) Syndromic craniosynostosis: from history to hydrogen bonds. Orthod Craniofac Res 10: 67-81. doi: 10.1111/j.1601-6343.2007.00389.x
    [161] El Ghouzzi V, Lajeunie E, Le Merrer M, et al. (1999) Mutations within or upstream of the basic helix-loop-helix domain of the TWIST gene are specific to Saethre-Chotzen syndrome. Europ J Hum Genet 7: 27-33. doi: 10.1038/sj.ejhg.5200240
    [162] Gripp KW, Zackai EH, Stolle CA (2000) Mutations in the human TWIST gene. Hum Mutat 15: 150-155, 2000.
    [163] Paznekas WA, Cunningham ML, Howard TD, et al. (1998) Genetic heterogeneity of Saethre-Chotzen syndrome, due to TWIST and FGFR mutations. Am J Hum Genet 62: 1370-1380. doi: 10.1086/301855
    [164] Johnson D, Iseki S, Wilkie AO, et al. (2000) Expression patterns of Twist and Fgfr1, -2 and -3 in the developing mouse coronal suture suggest a key role for twist in suture initiation and biogenesis. Mech Dev 91: 341-345. doi: 10.1016/S0925-4773(99)00278-6
    [165] Rice DP, Aberg T, Chan Y, et al. (2000) Integration of FGF and TWIST in calvarial bone and suture development. Development 127: 1845-1855.
    [166] Kress W, Schropp C, Lieb G, et al. (2006) Saethre-Chotzen syndrome caused by TWIST 1 gene mutations: functional differentiation from Muenke coronal synostosis syndrome. Eur J Hum Genet 14: 39-48.
    [167] Sharma VP, Fenwick AL, Brockop MS, et al. (2013) Mutations in TCF12, encoding a basic helix-loop-helix partner of TWIST1, are a frequent cause of coronal craniosynostosis. Nat Genet 45: 304-307. doi: 10.1038/ng.2531
    [168] Di Rocco F, Baujat G, Arnaud E, et al. (2014) Clinical spectrum and outcomes in families with coronal synostosis and TCF12 mutations. Eur J Hum Genet 22: 1413-1416.
    [169] Quintero-Rivera F, Robson CD, Reiss RE, et al. (2006) Intracranial anomalies detected by imaging studies in 30 patients with Apert syndrome. Am J Med Genet A 140: 1337-1338.
    [170] Meyers GA, Orlow SJ, Munro IR, et al. (1995) Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans. Nat Genet 11: 462-464. doi: 10.1038/ng1295-462
    [171] Arnaud-Lopez L, Fragoso R, Mantilla-Capacho J, et al. (2007) Crouzon with acanthosis nigricans: further delineation of the syndrome. Clin Genet 72: 405-410. doi: 10.1111/j.1399-0004.2007.00884.x
    [172] Cohen MM Jr (1999) Let's call it 'Crouzonodermoskeletal syndrome' so we won't be prisoners of our own conventional terminology. Am J Med Genet 84: 74.
    [173] Cohen MM Jr, Kreiborg S (1992) Birth prevalence studies of the Crouzon syndrome: comparison of direct and indirect methods. Clin Genet 41: 12-15.
    [174] Fernandes MB, Maximino LP, Perosa GB, et al. (2016) Apert and Crouzon syndromes-cognitive development, brain abnormalities, and molecular aspects. Am J Med Genet Ain press.
    [175] Cohen MM Jr (1993) Pfeiffer syndrome update, clinical subtypes, and guidelines for differential diagnosis. Am J Med Genet 45: 300-307. doi: 10.1002/ajmg.1320450305
    [176] Vogels A, Fryns JP (2006) Pfeiffer syndrome. Orphanet J Rare Dis 1: 19. doi: 10.1186/1750-1172-1-19
    [177] Jenkins D, Seelow D, Jehee FS, et al. (2007) RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesity. Am J Hum Genet 80: 1162-1170. doi: 10.1086/518047
    [178] Bellus GA, Gaudenz K, Zackai EH, et al. (1996) Identical mutations in three diferente fibroblast growth fator receptor genes in autosomal dominant craniosynostosis syndromes. Nat Genet 14: 174-176. doi: 10.1038/ng1096-174
    [179] Muenke M, Gripp KW, McDonald-McGinn DM, et al. (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.
    [180] Kruszka P, Addissie YA, Yarnell CM, et al. (2016) Muenke syndrome: An international multicenter natural history study. Am J Med Genet A in press.
    [181] Czeizel AE, Elek C, Susanszky E (1993) Birth prevalence study of Apert syndrome. Am J Med Genet 45: 392.
    [182] Orphanet report series, Prevalence of rare diseases: Bibliographic data. July 2015, Number 1. Available from:http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf
    [183] Carpenter syndrome. Available from: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=65759
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