Craniovertebral Junction Anomalies in Achondroplastic Children

  • Vincent Reina
  • Genevieve Baujat
  • Brigitte Fauroux
  • Vincent Couloigner
  • Elise Boulanger
  • Christian Sainte-Rose
  • Philippe Maroteaux
  • Martine Le Merrer
  • Valérie Cormier-Daire
  • Laurence Legai-Mallet
  • Michel Zerah
  • Federico Di Rocco
Part of the Advances and Technical Standards in Neurosurgery book series (NEUROSURGERY, volume 40)


The natural history of CVJ stenosis in achondroplastic children is only partially known. Achondroplastic children have a foramen magnum that is significatively smaller at birth, and it does not follow the normal growth during the first 18 months of life, leading to CVJ stenosis and, for the most severe of them, to neurological and developmental impairment and delay and even sudden death due to cervicomedullary narrowing. We reviewed our experience based on 37 patients operated for cervicomedullary decompression between 1970 and 2010 and performed a literature review. The indication for surgery should be taken on very strict clinical and radiological parameters as well as sleep studies. Under those criteria, surgical decompression of CVJ leads to neurological and developmental improvement, despite non-negligible mortality and morbidity.


Achondroplasia Cranio-cervical junction Sudden death Foramen magnum decompression 


  1. 1.
    Aryanpur J, Hurko O, Francomano C, Wang H, Carson B (1990) Craniocervical decompression for cervicomedullary compression in pediatric patients with achondroplasia. J Neurosurg 73:375–382PubMedCrossRefGoogle Scholar
  2. 2.
    Bagley CA, Pindrik JA, Bookland MJ, Camara-Quintana JQ, Carson BS (2006) Cervicomedullary decompression for foramen magnum stenosis in achondroplasia. J Neurosurg 104:166–172PubMedGoogle Scholar
  3. 3.
    Colamaria V, Mazza C, Beltramello A, Polo A, Boner A, Antoniazzi F, Polo M, Luchini P, Sgrò V, Dalla Bernardina B (1991) Irreversible respiratory failure in an achondroplastic child: the importance of an early cervicomedullary decompression, and a review of the literature. Brain Dev 13:270–279PubMedCrossRefGoogle Scholar
  4. 4.
    Delezoide AL, Benoist-Lasselin C, Legeai-Mallet L, Le Merrer M, Munnich A, Vekemans M, Bonaventure J (1998) Spatio-temporal expression of FGFR 1, 2 and 3 genes during human embryo-fetal ossification. Mech Dev 77:19–30PubMedCrossRefGoogle Scholar
  5. 5.
    Dennis JP, Rosenberg HS, Alvord EC Jr (1961) Megalencephaly, internal hydrocephalus and other neurological aspects of achondroplasia. Brain 84:427–445PubMedCrossRefGoogle Scholar
  6. 6.
    Friedman WA, Mickle JP (1980) Hydrocephalus in achondroplasia: a possible mechanism. Neurosurgery 7:150–153PubMedCrossRefGoogle Scholar
  7. 7.
    Harada D, Yamanaka Y, Ueda K, Tanaka H, Seino Y (2009) FGFR3-related dwarfism and cell signaling. J Bone Miner Metab 27:9–15PubMedCrossRefGoogle Scholar
  8. 8.
    Hecht JT, Nelson FW, Butler IJ, Horton WA, Scott CI Jr, Wassman ER, Mehringer CM, Rimoin DL, Pauli RM (1985) Computerized tomography of the foramen magnum: achondroplastic values compared to normal standards. Am J Med Genet 20:355–360PubMedCrossRefGoogle Scholar
  9. 9.
    Hecht JT, Francomano CA, Horton WA, Annegers JF (1987) Mortality in achondroplasia. Am J Hum Genet 41:454–464PubMedCentralPubMedGoogle Scholar
  10. 10.
    Hecht JT, Horton WA, Reid CS, Pyeritz RE, Chakraborty R (1989) Growth of the foramen magnum in achondroplasia. Am J Med Genet 32:528–535PubMedCrossRefGoogle Scholar
  11. 11.
    Helms JA, Amasha RR, Leucht P (2007) Bone voyage: an expedition into the molecular and cellular parameters affecting bone graft fate. Bone 41:479–485PubMedCrossRefGoogle Scholar
  12. 12.
    Horton WA, Hall JG, Hecht JT (2007) Achondroplasia. Lancet 370:162–172PubMedCrossRefGoogle Scholar
  13. 13.
    Horton WA, Degnin CR (2009) FGFs in endochondral skeletal development. Trends Endocrinol Metab 20:341–348PubMedCrossRefGoogle Scholar
  14. 14.
    Iwata T, Hevner RF (2009) Fibroblast growth factor signaling in development of the cerebral cortex. Dev Growth Differ 51:299–323PubMedCrossRefGoogle Scholar
  15. 15.
    Julliand S, Boulé M, Baujat G, Ramirez A, Couloigner V, Beydon N, Zerah M, Di Rocco F, Lemerrer M, Cormier-Daire V et al (2012) Lung function, diagnosis, and treatment of sleep-disordered breathing in children with achondroplasia. Am J Med Genet A 158A:1987–1993PubMedCrossRefGoogle Scholar
  16. 16.
    Keiper GL Jr, Koch B, Crone KR (1999) Achondroplasia and cervicomedullary compression: prospective evaluation and surgical treatment. Pediatr Neurosurg 31:78–83PubMedCrossRefGoogle Scholar
  17. 17.
    King JAJ, Vachhrajani S, Drake JM, Rutka JT (2009) Neurosurgical implications of achondroplasia. J Neurosurg Pediatr 4:297–306PubMedCrossRefGoogle Scholar
  18. 18.
    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 36:9–13PubMedCentralPubMedGoogle Scholar
  19. 19.
    Marin-Padilla M, Marin-Padilla TM (1977) Developmental abnormalities of the occipital bone in human chondrodystrophies (achondroplasia and thanatophoric dwarfism). Birth Defects Orig Artic Ser 13:7–23PubMedGoogle Scholar
  20. 20.
    Menezes AH (2004) Evaluation and treatment of congenital and developmental anomalies of the cervical spine. Invited submission from the Joint Section Meeting on Disorders of the Spine and Peripheral Nerves, March 2004. J Neurosurg Spine 1:188–197PubMedCrossRefGoogle Scholar
  21. 21.
    Menezes AH (2005) Honored guest presentation: craniocervical developmental anatomy and its implications. Clin Neurosurg 52:53–64PubMedGoogle Scholar
  22. 22.
    Menezes AH (2008) Craniocervical developmental anatomy and its implications. Childs Nerv Syst 24:1109–1122PubMedCrossRefGoogle Scholar
  23. 23.
    Menezes AH (2009) Editorial. Achondroplasia. J Neurosurg Pediatr 4:295–296; discussion 296PubMedCrossRefGoogle Scholar
  24. 24.
    Meyers GA, Orlow SJ, Munro IR, Przylepa KA, Jabs EW (1995) Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans. Nat Genet 11:462–464PubMedCrossRefGoogle Scholar
  25. 25.
    Muenke M, Gripp KW, McDonald-McGinn DM, Gaudenz K, Whitaker LA, Bartlett SP, Markowitz RI, Robin NH, Nwokoro N, Mulvihill JJ 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 60:555–564PubMedCentralPubMedGoogle Scholar
  26. 26.
    Pauli RM, Scott CI, Wassman ER Jr, Gilbert EF, Leavitt LA, Ver Hoeve J, Hall JG, Partington MW, Jones KL, Sommer A (1984) Apnea and sudden unexpected death in infants with achondroplasia. J Pediatr 104:342–348PubMedCrossRefGoogle Scholar
  27. 27.
    Pauli RM, Horton VK, Glinski LP, Reiser CA (1995) Prospective assessment of risks for cervicomedullary-junction compression in infants with achondroplasia. Am J Hum Genet 56:732–744PubMedCentralPubMedGoogle Scholar
  28. 28.
    Pierre-Kahn A, Hirsch JF, Renier D, Metzger J, Maroteaux P (1980) Hydrocephalus and achondroplasia. A study of 25 observations. Childs Brain 7:205–219PubMedGoogle Scholar
  29. 29.
    Reid CS, Pyeritz RE, Kopits SE, Maria BL, Wang H, McPherson RW, Hurko O, Phillips JA 3rd, Rosenbaum AE (1987) Cervicomedullary compression in young patients with achondroplasia: value of comprehensive neurologic and respiratory evaluation. J Pediatr 110:522–530PubMedCrossRefGoogle Scholar
  30. 30.
    Renier D, El-Ghouzzi V, Bonaventure J, Le Merrer M, Lajeunie E (2000) Fibroblast growth factor receptor 3 mutation in nonsyndromic coronal synostosis: clinical spectrum, prevalence, and surgical outcome. J Neurosurg 92:631–636PubMedCrossRefGoogle Scholar
  31. 31.
    Rimoin DL (1995) Cervicomedullary junction compression in infants with achondroplasia: when to perform neurosurgical decompression. Am J Hum Genet 56:824–827PubMedCentralPubMedGoogle Scholar
  32. 32.
    Di Rocco F, Collet C, Legeai-Mallet L, Arnaud E, Le Merrer M, Hadj-Rabia S, Renier D (2011) Crouzon syndrome with acanthosis nigricans: a case-based update. Childs Nerv Syst 27:349–354PubMedCrossRefGoogle Scholar
  33. 33.
    Rousseau F, Bonaventure J, Legeai-Mallet L, Pelet A, Rozet JM, Maroteaux P, Le Merrer M, Munnich A (1994) Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia. Nature 371:252–254PubMedCrossRefGoogle Scholar
  34. 34.
    Ryken TC, Menezes AH (1994) Cervicomedullary compression in achondroplasia. J Neurosurg 81:43–48PubMedCrossRefGoogle Scholar
  35. 35.
    Sabatino G, Di Rocco F, Zampino G, Tamburrini G, Caldarelli M, Di Rocco C (2004) Muenke syndrome. Childs Nerv Syst 20:297–301PubMedCrossRefGoogle Scholar
  36. 36.
    Sainte-Rose C, LaCombe J, Pierre-Kahn A, Renier D, Hirsch JF (1984) Intracranial venous sinus hypertension: cause or consequence of hydrocephalus in infants. J Neurosurg 60:727–736PubMedCrossRefGoogle Scholar
  37. 37.
    Sainte-Rose C, Servant JM, Mayer M, Hirsch JF (1989) Hydrocephalus of venous origin. Neurochirurgie 35:383–389, 410PubMedGoogle Scholar
  38. 38.
    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 78:335–342PubMedCrossRefGoogle Scholar
  39. 39.
    Stanescu R, Stanescu V, Maroteaux P (1990) Homozygous achondroplasia: morphologic and biochemical study of cartilage. Am J Med Genet 37:412–421PubMedCrossRefGoogle Scholar
  40. 40.
    Velinov M, Slaugenhaupt SA, Stoilov I, Scott CI Jr, Gusella JF, Tsipouras P (1994) The gene for achondroplasia maps to the telomeric region of chromosome 4p. Nat Genet 6:314–317PubMedCrossRefGoogle Scholar
  41. 41.
    Yamada H, Nakamura S, Tajima M, Kageyama N (1981) Neurological manifestations of pediatric achondroplasia. J Neurosurg 54:49–57PubMedCrossRefGoogle Scholar
  42. 42.
    Yamada Y, Ito H, Otsubo Y, Sekido K (1996) Surgical management of cervicomedullary compression in achondroplasia. Childs Nerv Syst 12:737–741PubMedCrossRefGoogle Scholar
  43. 43.
    Yang SS, Corbett DP, Brough AJ, Heidelberger KP, Bernstein J (1977) Upper cervical myelopathy in achondroplasia. Am J Clin Pathol 68:68–72PubMedGoogle Scholar
  44. 44.
    Pang D, Thompson DN. Embryology and bony malformations of the craniovertebral junction. Childs Nerv Syst 2011;27(4):523–64PubMedCentralPubMedCrossRefGoogle Scholar
  45. 45.
    Menezes AH. Craniocervical developmental anatomy and its implications. Childs Nerv Syst 2008;24(10):1109–22PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Vincent Reina
    • 1
  • Genevieve Baujat
    • 2
  • Brigitte Fauroux
    • 3
    • 4
  • Vincent Couloigner
    • 3
  • Elise Boulanger
    • 1
  • Christian Sainte-Rose
    • 1
  • Philippe Maroteaux
    • 2
  • Martine Le Merrer
    • 2
  • Valérie Cormier-Daire
    • 2
  • Laurence Legai-Mallet
    • 2
  • Michel Zerah
    • 1
  • Federico Di Rocco
    • 1
  1. 1.Pediatric Neurosurgical DepartementHôpital Necker-Enfants Malades, APHPParisFrance
  2. 2.Genetic DepartmentNational Reference Centre for Congenital Bone Diseases, Hôpital Necker-Enfants Malades, INSERM U781ParisFrance
  3. 3.Otorhinolaryngology DepartmentHôpital Necker-Enfants MaladesParisFrance
  4. 4.Unité de ventilation non-invasive et du sommeil de l’enfant, INSERM U 955, Hôpital Necker-Enfants MaladesParisFrance

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