Abstract
Purpose
Crouzon syndrome is a complex craniosynostosis of autosomal dominant transfer, with a highly variable phenotypic appearance. Some patients are afflicted with a mild form of the disease and able to live a fully functional lifestyle, whereas many patients suffer from a severe form of the disease causing a significant impact on their quality of life. Although several case reports and genetic studies have been performed, there has been no recent review of the literature to collate the information on this disorder. In this paper, we seek to unify the findings of this disorder to provide the pediatric provider with a succinct, but complete discussion of this disease.
Methods
Articles from 1994 to 2014 were queried on PubMed and reviewed for utility by all three researchers involved in the project. Further literature review was done on relevant articles found within references of selected articles.
Results
Crouzon syndrome, although of variable penetrance, is thought to be caused in part by a mutation in the fibroblast growth factor receptor-2 (FGFR2) on chromosome 10. Aside from craniofacial malformations, the disease can also cause hearing loss and airway challenges due to malformations in the nasal cavity and nasopharyngeal airway. Management options from the perspective of the otorhinolaryngologist are diverse and revolve around craniosynostectomy, offsetting midfacial hypoplasia, addressing obstructive sleep apnea and a compromised airway, psychosocial and esthetic interventions, and ultimately requiring a multidisciplinary team approach.
Conclusion
Mutations in the FGFR2 are responsible for 50 % of mutations within this multifaceted syndrome. Crouzon syndrome is an autosomal dominant disorder with a number of distinguishing characteristics, including craniosynostosis, maxillary hypoplasia, exophthalmos, and multiple other features. Early intervention, both medically and surgically, as well as disciplined follow-up with the pediatric provider are crucial to the management of this disorder. In particular, management should address cranial suture release, midfacial advancement, evaluation for hearing deficits, and obstructive sleep apnea, with expedient intervention for airway compromise and increased intracranial pressure.
Similar content being viewed by others
References
Crouzon O (1912) Dyostose craniofacial hereditaire. Bull Mem Soc Med Hop Paris 33:545
Bowling EL, Burstein FD (2006) Crouzon syndrome. Optometry (St Louis, Mo) 77(5):217–222
Horbelt CV (2008) Physical and oral characteristics of Crouzon syndrome, Apert syndrome, and Pierre Robin sequence. Gen Dent 56(2):132–134
Cohen MM Jr, Kreiborg S (1992) Birth prevalence studies of the Crouzon syndrome: comparison of direct and indirect methods. Clin Genet 41(1):12–15
Cohen MM Jr (1988) Craniosynostosis update 1987. Am J Med Genet Suppl 4:99–148
Pagnoni M, Fadda MT, Spalice A et al. (2013) Surgical timing of craniosynostosis: what to do and when. J Cranio-Maxillo-Facial Surg Offic Pub Eur Assoc Cranio-Maxillo-Facial Surg. Sep 2 2013
Shiller JG (1959) Craniofacial dysostosis of Crouzon; a case report and pedigree with emphasis on heredity. Pediatrics 23(1 Part 1):107–112
Reardon W, Winter RM, Rutland P, Pulleyn LJ, Jones BM, Malcolm S (1994) Mutations in the fibroblast growth factor receptor 2 gene cause Crouzon syndrome. Nat Genet 8(1):98–103
Gault DT, Renier D, Marchac D, Jones BM (1992) Intracranial pressure and intracranial volume in children with craniosynostosis. Plast Reconstr Surg 90(3):377–381
Cinalli G, Renier D, Sebag G, Sainte-Rose C, Arnaud E, Pierre-Kahn A (1995) Chronic tonsillar herniation in Crouzon’s and Apert’s syndromes: the role of premature synostosis of the lambdoid suture. J Neurosurg 83(4):575–582
Cohen SR, Dauser RC, Gorski JL (1993) Insidious onset of familial craniosynostosis. Cleft Palate-Craniofac J Offic Pub Am Cleft Palate-Craniofac Assoc 30(4):401–405
Devine P, Bhan I, Feingold M, Leonidas JC, Wolpert SM (1984) Completely cartilaginous trachea in a child with Crouzon syndrome. Am J Dis Child 138(1):40–43
Park WJ, Meyers GA, Li X et al (1995) Novel FGFR2 mutations in Crouzon and Jackson-Weiss syndromes show allelic heterogeneity and phenotypic variability. Hum Mol Genet 4(7):1229–1233
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(3):275–279
Gilbert E, Del Gatto F, Champion-Arnaud P, Gesnel MC, Breathnach R (1993) Control of BEK and K-SAM splice sites in alternative splicing of the fibroblast growth factor receptor 2 pre-mRNA. Mol Cell Biol 13(9):5461–5468
Sharma VP, Wall SA, Lord H, Lester T, Wilkie AO (2012) Atypical Crouzon syndrome with a novel Cys62Arg mutation in FGFR2 presenting with sagittal synostosis. Cleft Palate-Craniofac J Offic Pub Am Cleft Palate-Craniofac Assoc 49(3):373–377
Muenke M, Schell U (1995) Fibroblast-growth-factor receptor mutations in human skeletal disorders. Trends Genet TIG 11(8):308–313
Steinberger D, Mulliken JB, Muller U (1995) Predisposition for cysteine substitutions in the immunoglobulin-like chain of FGFR2 in Crouzon syndrome. Hum Genet 96(1):113–115
Hatch NE, Hudson M, Seto ML, Cunningham ML, Bothwell M (2006) Intracellular retention, degradation, and signaling of glycosylation-deficient FGFR2 and craniosynostosis syndrome-associated FGFR2C278F. J Biol Chem 281(37):27292–27305
Warren SM, Brunet LJ, Harland RM, Economides AN, Longaker MT (2003) The BMP antagonist noggin regulates cranial suture fusion. Nature 422(6932):625–629
Dab S, Sokhi R, Lee JC, Sessle BJ, Aubin JE, Gong SG (2013) Characterization of esophageal defects in the Crouzon mouse model. Birth Defects Res A Clin Mol Teratol 97(9):578–586
Virchow R (1851) Über den Cretinismus, namentlich in Franken, und ueberpathologische Schädelformen. Verh Phys Med Ges Würzburg 2:230–271
al-Qattan MM, Phillips JH (1997) Clinical features of Crouzon’s syndrome patients with and without a positive family history of Crouzon’s syndrome. J Craniofac Surg 8(1):11–13
Anderson PJ, Hall CM, Evans RD, Jones BM, Hayward RD (1997) Hand anomalies in Crouzon syndrome. Skeletal Radiol 26(2):113–115
Vulliamy DG, Normandale PA (1966) Cranio-facial dysostosis in a dorset family. Arch Dis Child 41(218):375–382
Glaser RL, Jiang W, Boyadjiev SA et al (2000) Paternal origin of FGFR2 mutations in sporadic cases of Crouzon syndrome and Pfeiffer syndrome. Am J Hum Genet 66(3):768–777
Juberg RC, Chambers SR (1973) An autosomal recessive form of craniofacial dysostosis (the Crouzon syndrome). J Med Genet 10(1):89–94
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(4):462–464
Ahmed I, Afzal A (2009) Diagnosis and evaluation of Crouzon syndrome. J Coll Physicians Surg Pak JCPSP 19(5):318–320
Nur BG, Pehlivanoglu S, Mihci E et al (2014) Clinicogenetic study of Turkish patients with syndromic craniosynostosis and literature review. Pediatr Neurol 50(5):482–490
Abou-Sleiman PM, Apessos A, Harper JC, Serhal P, Delhanty JD (2002) Pregnancy following preimplantation genetic diagnosis for Crouzon syndrome. Mol Hum Reprod 8(3):304–309
Schwartz M, Kreiborg S, Skovby F (1996) First-trimester prenatal diagnosis of Crouzon syndrome. Prenat Diagn 16(2):155–158
Menashe Y, Ben Baruch G, Rabinovitch O, Shalev Y, Katzenlson MB, Shalev E (1989) Exophthalmus–prenatal ultrasonic features for diagnosis of Crouzon syndrome. Prenat Diagn 9(11):805–808
Canpolat A, Akcakaya MO, Altunrende E et al (2014) Chiari type I malformation yielded to the diagnosis of Crouzon syndrome. J Neurosci Rural Pract 5(1):81–83
Cohen MM Jr, Kreiborg S, Lammer EJ et al (1992) Birth prevalence study of the Apert syndrome. Am J Med Genet 42(5):655–659
Cohen MM Jr (1993) Pfeiffer syndrome update, clinical subtypes, and guidelines for differential diagnosis. Am J Med Genet 45(3):300–307
Pantke OA, Cohen MM Jr, Witkop CJ Jr et al (1975) The saethre-chotzen syndrome. Birth Defects Orig Artic Ser 11(2):190–225
Allam KA, Wan DC, Khwanngern K et al (2011) Treatment of Apert syndrome: a long-term follow-up study. Plast Reconstr Surg 127(4):1601–1611
Renier D, Sainte-Rose C, Marchac D, Hirsch JF (1982) Intracranial pressure in craniostenosis. J Neurosurg 57(3):370–377
Dobbs TD, Wall SA, Richards PG, Johnson D (2014) A novel technique to secure the rigid external distraction (RED) frame in a thin skull allowing sutural mid-face distraction. J Cranio-Maxillo-Facial Surg Offic Pub Eur Assoc Cranio-Maxillo-Facial Surg. Jan 15 2014
Tamburrini G, Caldarelli M, Massimi L, Santini P, Di Rocco C (2005) Intracranial pressure monitoring in children with single suture and complex craniosynostosis: a review. Child’s Nerv Syst ChNS Offic J Int Soc PediatrNeurosurg 21(10):913–921
Renier D, Lajeunie E, Arnaud E, Marchac D (2000) Management of craniosynostoses. Child’s Nerv Syst ChNS Offic J Int Soc PediatrNeurosurg 16(10–11):645–658
Perlyn CA, Marsh JL (2008) Craniofacial dysmorphology of carpenter syndrome: lessons from three affected siblings. Plast Reconstr Surg 121(3):971–981
Jamil MN, Bannister CM, Ward G (1992) Carpenter’s syndrome (acrocephalopolysyndactyly type II) with normal intelligence. Br J Neurosurg 6(3):243–247
Der Kaloustian VM, Sinno AA, Nassar SI (1972) Acrocephalopolysyndactyly, type II (carpenter syndrome). Am J Dis Child 124(5):716–718
Eaton AP, Sommer A, Kontras SB, Sayers MP (1974) Carpenter syndrome–acrocephalopolysyndactyly type II. Birth Defects Orig Artic Ser 10(9):249–260
Robinson LK, James HE, Mubarak SJ, Allen EJ, Jones KL (1985) Carpenter syndrome: natural history and clinical spectrum. Am J Med Genet 20(3):461–469
Hidestrand P, Vasconez H, Cottrill C (2009) Carpenter syndrome. J Craniofac Surg 20(1):254–256
Alessandri JL, Dagoneau N, Laville JM, Baruteau J, Hebert JC, Cormier-Daire V (2010) RAB23 mutation in a large family from comoros islands with carpenter syndrome. Am J Med Genet A 152a(4):982–986
Yamaguchi K, Imai K, Fujimoto T et al (2014) Cranial distraction osteogenesis for syndromic craniosynostosis: long-term follow-up and effect on postoperative cranial growth. J Plast Reconstr Aesthet Surg JPRAS 67(2):e35–e41
Lee DW, Ham KW, Kwon SM, Lew DH, Cho EJ (2012) Dual midfacial distraction osteogenesis for Crouzon syndrome: long-term follow-up study for relapse and growth. J Oral Maxillofac Surg Offic J Am Assoc Oral Maxillofac Surg 70(3):e242–e251
Fischer S, Tovetjarn R, Maltese G, Sahlin PE, Tarnow P, Kolby L (2013) Psychosocial conditions in adults with Crouzon syndrome: a follow-up study of 31 Swedish patients. J Plast Surg Hand Surg. Dec 16 2013
Jacobsen HC, Sieg P, Hakim S (2009) Combined internal and external distraction of the midface for the treatment of Crouzon syndrome and critical obstructive sleep apnea: a case report. J Oral Maxillofac Surg Offic J Am Assoc Oral Maxillofac Surg 67(9):2004–2009
Fearon JA, Whitaker LA (1993) Complications with facial advancement: a comparison between the Le Fort III and monobloc advancements. Plast Reconstr Surg 91(6):990–995
Sakamoto Y, Nakajima H, Tamada I, Sakamoto T (2014) Le Fort IV+I distraction osteogenesis using an internal device for syndromic craniosynostosis. J Oral Maxillofac Surg Offic J Am Assoc Oral Maxillofac Surg 72(4):788–795
Meling TR, Hogevold HE, Due-Tonnessen BJ, Skjelbred P (2011) Comparison of perioperative morbidity after LeFort III and monobloc distraction osteogenesis. Br J Oral Maxillofac Surg 49(2):131–134
Mitsukawa N, Satoh K, Hayashi T, Furukawa Y, Uemura T, Hosaka Y (2004) A reflectable case of obstructive sleep apnea in an infant with Crouzon syndrome. J Craniofac Surg 15(5):874–878, discussion 878–879
Conflict of interest
No financial disclosure or obligations to declare
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Helman, S.N., Badhey, A., Kadakia, S. et al. Revisiting Crouzon syndrome: reviewing the background and management of a multifaceted disease. Oral Maxillofac Surg 18, 373–379 (2014). https://doi.org/10.1007/s10006-014-0467-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10006-014-0467-0