Skip to main content

Advertisement

SpringerLink
Log in

Severe craniolacunae and upper and lower extremity anomalies resulting from Crouzon syndrome, FGFR2 mutation, and Ser347Cys variant

  • Case Report
  • Published:
Child's Nervous System Aims and scope Submit manuscript

Abstract

Crouzon syndrome is a rare form of syndromic craniosynostosis (SC) characterized by premature fusion of the cranial and facial sutures, elevated intracranial pressure, varying degrees of ocular exposure due to exorbitism, and airway compromise caused by midface retrusion. Craniolacunae and upper and lower extremity anomalies are not frequently found in Crouzon syndrome. We present a girl with Crouzon syndrome caused by c.1040 C > G, p.Ser347Cys, a pathogenic mutation in the FGFR2 gene with atypical characteristics, including craniolacunae resembling severe Swiss cheese type of bone formation, and upper and lower extremity anomalies which are more commonly associated with Pfeiffer syndrome patients. Distinguishing between severe Crouzon syndrome patients and patients who have mild and/or moderate Pfeiffer syndrome can be challenging even for an experienced craniofacial surgeon. An accurate genotype diagnosis is essential to distinguishing between these syndromes, as it provides predictors for neurosurgical complications and facilitates appropriate family counseling related to long-term outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Allam KA, Wan DC, Khwanngern K, Kawamoto HK, Tanna N, Perry A, Bradley JP (2011) Treatment of Apert syndrome: a long-term follow-up study. Plast Reconstr Surg 127:1601–1611. https://doi.org/10.1097/PRS.0b013e31820a64b6

    Article  CAS  PubMed  Google Scholar 

  2. Al-Namnam NM, Hariri F, Thong MK, Rahman ZA (2019) Crouzon syndrome: genetic and intervention review. J Oral Biol Craniofac Res 9:37–39. https://doi.org/10.1016/j.jobcr.2018.08.007

    Article  CAS  PubMed  Google Scholar 

  3. Ariga H, Endo Y, Ujiie N, Ishii T, Ishibashi N, Fujita T, Suzuki H (2001) Trp290Cys mutation of the FGFR2 gene in a patient with severe Pfeiffer syndrome type 2. Pediatr Int 43:293–295. https://doi.org/10.1046/j.1442-200x.2001.01379.x

    Article  CAS  PubMed  Google Scholar 

  4. Azoury SC, Reddy S, Shukla V, Deng CX (2017) Fibroblast growth factor receptor 2 (FGFR2) mutation related syndromic craniosynostosis. Int J Biol Sci 13:1479–1488. https://doi.org/10.7150/ijbs.22373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Barry GP, Ny BM, Zackai EH, Grunwald L, Forbes BJ (2010) A case report of a patient with Pfeiffer syndrome, an FGRF 2 mutation (Trp290Cys) and unique ocular anterior segment findings. Ophthalmic Genet 31:193–195. https://doi.org/10.3109/13816810.2010.505225

    Article  CAS  PubMed  Google Scholar 

  6. Cerrato FE, Nuzzi LC, Theman TA, Taghinia A, Upton J, Labow BI (2014) Upper extremity anomalies in Pfeiffer syndrome and mutational correlations. Plast Reconstr Surg 133:654e–661e. https://doi.org/10.1097/PRS.0000000000000107

    Article  CAS  PubMed  Google Scholar 

  7. Choi M, Flores RL, Havlik RJ (2012) Volumetric analysis of anterior versus posterior cranial vault expansion in patients with syndromic craniosynostosis. J Craniofac Surg 23:455–458. https://doi.org/10.1097/SCS.0b013e318240ff49

    Article  PubMed  Google Scholar 

  8. Cohen MM Jr (2001) Jackson-Weiss syndrome. Am J Med Genet 100:325–329. https://doi.org/10.1002/ajmg.1271

    Article  PubMed  Google Scholar 

  9. Derderian CA, Bastidas N, Bartlett SP (2012) Posterior cranial vault expansion using distraction osteogenesis. Childs Nerv Syst 28:1551–1556. https://doi.org/10.1007/s00381-012-1802-0

    Article  PubMed  Google Scholar 

  10. Derderian CA, Wink JD, McGrath JL, Collinsworth A, Bartlett SP, Taylor JA (2015) Volumetric changes in cranial vault expansion: comparison of fronto-orbital advancement and posterior cranial vault distraction osteogenesis. Plast Reconstr Surg 135:1665–1672. https://doi.org/10.1097/PRS.0000000000001294

    Article  CAS  PubMed  Google Scholar 

  11. Fearon JA, Podner C (2013) Apert syndrome: evaluation of a treatment algorithm. Plast Reconstr Surg 131:132–142. https://doi.org/10.1097/PRS.0b013e3182729f42

    Article  CAS  PubMed  Google Scholar 

  12. Fearon JA, Rhodes J (2009) Pfeiffer syndrome: a treatment evaluation. Plast Reconstr Surg 123:1560–1569. https://doi.org/10.1097/PRS.0b013e3181a2057e

    Article  CAS  PubMed  Google Scholar 

  13. Greig AV, Wagner J, Warren SM, Grayson B, McCarthy JG (2013) Pfeiffer syndrome: analysis of a clinical series and development of a classification system. J Craniofac Surg 24:204–215. https://doi.org/10.1097/SCS.0b013e31826704be

    Article  PubMed  Google Scholar 

  14. Heike C, Seto M, Hing A, Palidin A, Hu FZ, Preston RA, Ehrlich GD, Cunningham M (2001) Century of Jackson-Weiss syndrome: further definition of clinical and radiographic findings in “lost” descendants of the original kindred. Am J Med Genet 100:315–324. https://doi.org/10.1002/ajmg.1266

    Article  CAS  PubMed  Google Scholar 

  15. Hollway GE, Suthers GK, Haan EA, Thompson E, David DJ, Gecz J, Mulley JC (1997) Mutation detection in FGFR2 craniosynostosis syndromes. Hum Genet 99:251–255. https://doi.org/10.1007/s004390050348

    Article  CAS  PubMed  Google Scholar 

  16. Jabs EW, Li X, Scott AF, Meyers G, Chen W, Eccles M, Mao JI, Charnas LR, Jackson CE, Jaye M (1994) Jackson-Weiss and Crouzon syndromes are allelic with mutations in fibroblast growth factor receptor 2. Nat Genet 8:275–279. https://doi.org/10.1038/ng1194-275

    Article  CAS  PubMed  Google Scholar 

  17. Lajeunie E, Heuertz S, El Ghouzzi V, Martinovic J, Renier D, Le Merrer M, Bonaventure J (2006) Mutation screening in patients with syndromic craniosynostosis indicates that a limited number of recurrent FGFR2 mutations accounts for severe forms of Pfeiffer syndrome. Eur J Hum Genet 14:289–298. https://doi.org/10.1038/sj.ejhg.5201558

    Article  CAS  PubMed  Google Scholar 

  18. Marchac D, Renier D (1979) The “floating forehead”. Early treatment of craniofacial stenosis. Ann Chir Plast 24:121–126

    CAS  PubMed  Google Scholar 

  19. Marchac D, Renier D, Jones BM (1988) Experience with the “floating forehead.” Br J Plast Surg 41:1–15. https://doi.org/10.1016/0007-1226(88)90137-3

  20. Mondal A, Rodriguez-Florez N, O’Hara J, Ong J, Jeelani NUO, Dunaway DJ, James G (2019) Lack of association of cranial lacunae with intracranial hypertension in children with Crouzon syndrome and Apert syndrome: a 3D morphometric quantitative analysis. Childs Nerv Syst 35:501–507. https://doi.org/10.1007/s00381-019-04059-6

  21. Ohishi A, Nishimura G, Kato F, Ono H, Maruwaka K, Ago M, Suzumura H, Hirose E, Uchida Y, Fukami M, Ogata T (2017) Mutation analysis of FGFR1-3 in 11 Japanese patients with syndromic craniosynostosis. Am J Med Genet A 173:157–162. https://doi.org/10.1002/ajmg.a.37992

    Article  CAS  PubMed  Google Scholar 

  22. Oldridge M, Wilkie AO, Slaney SF, Poole MD, Pulleyn LJ, Rutland P, Hockley AD, Wake MJ, Goldin JH, Winter RM et al (1995) Mutations in the third immunoglobulin domain of the fibroblast growth factor receptor-2 gene in Crouzon syndrome. Hum Mol Genet 4:1077–1082. https://doi.org/10.1093/hmg/4.6.1077

    Article  CAS  PubMed  Google Scholar 

  23. Passos-Bueno MR, Sertie AL, Zatz M, Richieri-Costa A (1997) Pfeiffer mutation in an Apert patient: how wide is the spectrum of variability due to mutations in the FGFR2 gene? Am J Med Genet 71:243–245

    Article  CAS  Google Scholar 

  24. Passos-Bueno MR, Wilcox WR, Jabs EW, Sertie AL, Alonso LG, Kitoh H (1999) Clinical spectrum of fibroblast growth factor receptor mutations. Hum Mutat 14:115–125. https://doi.org/10.1002/(SICI)1098-1004(1999)14:2%3c115::AID-HUMU3%3e3.0.CO;2-2

  25. Patel PA, Shetye PR, Warren SM, Grayson BH, McCarthy JG (2017) Five-year follow-up of midface distraction in growing children with syndromic craniosynostosis. Plast Reconstr Surg 140:794e–803e. https://doi.org/10.1097/PRS.0000000000003879

    Article  CAS  PubMed  Google Scholar 

  26. Raposo-Amaral CE, Raposo-Amaral CA, Garcia Neto JJ, Farias DB, Somensi RS (2012) Apert syndrome: quality of life and challenges of a management protocol in Brazil. J Craniofac surgery 23:1104–1108. https://doi.org/10.1097/SCS.0b013e318258814a

    Article  Google Scholar 

  27. Raposo-Amaral CE, Denadai R, Ghizoni E, Buzzo CL, Raposo-Amaral CA (2015) Family of Crouzon syndrome represents the evolution of the frontofacial monobloc advancement technique: from immediate movement to monobloc distraction to monobloc bipartition distraction. J Craniofac Surg 26:1940–1943. https://doi.org/10.1097/SCS.0000000000001949

    Article  PubMed  Google Scholar 

  28. Raposo-Amaral CE, Denadai R, Furlan P, Raposo-Amaral CA (2018) Treatment of Apert hand syndrome: strategies for achieving a five-digit hand. Plast Reconstr Surg 142:972–982. https://doi.org/10.1097/PRS.0000000000004815

    Article  CAS  PubMed  Google Scholar 

  29. Raposo-Amaral CE, Denadai R, de Oliveira YM, Ghizoni E, Raposo-Amaral CA (2019) Apert syndrome management: changing treatment algorithm. J Craniofac Surg. https://doi.org/10.1097/SCS.0000000000006105

    Article  PubMed  PubMed Central  Google Scholar 

  30. Raposo-Amaral CE, Denadai R, Ghizoni E, Raposo-Amaral CA (2019) Treating craniofacial dysostoses with hypertelorism by monobloc facial bipartition distraction: surgical and educational videos. Plast Reconstr Surg 144:433–438. https://doi.org/10.1097/PRS.0000000000005859

    Article  CAS  PubMed  Google Scholar 

  31. Raposo-Amaral CE, Denadai R, Zanco GL, Ghizoni E, Raposo-Amaral CA (2020) Long-term follow-up on bone stability and complication rate after monobloc advancement in syndromic craniosynostosis. Plast Reconstr Surg 145:1025–1034. https://doi.org/10.1097/PRS.0000000000006646

    Article  CAS  PubMed  Google Scholar 

  32. Raposo-Amaral CE, Denadai R, Maximo G, Raposo-Amaral CA, Ghizoni E (2020) Pfeiffer syndrome: a therapeutic algorithm based on a modified grading scale. Plast Reconstr Surg Glob Open 8:e2788. https://doi.org/10.1097/GOX.0000000000002788

    Article  PubMed  PubMed Central  Google Scholar 

  33. Roscioli T, Elakis G, Cox TC, Moon DJ, Venselaar H, Turner AM, Le T, Hackett E, Haan E, Colley A, Mowat D, Worgan L, Kirk EP, Sachdev R, Thompson E, Gabbett M, McGaughran J, Gibson K, Gattas M, Freckmann ML, Dixon J, Hoefsloot L, Field M, Hackett A, Kamien B, Edwards M, Ades LC, Collins FA, Wilson MJ, Savarirayan R, Tan TY, Amor DJ, McGillivray G, White SM, Glass IA, David DJ, Anderson PJ, Gianoutsos M, Buckley MF (2013) Genotype and clinical care correlations in craniosynostosis: findings from a cohort of 630 Australian and New Zealand patients. Am J Med Genet C Semin Med Genet 163C:259–270. https://doi.org/10.1002/ajmg.c.31378

    Article  CAS  PubMed  Google Scholar 

  34. Schaefer F, Anderson C, Can B, Say B (1998) Novel mutation in the FGFR2 gene at the same codon as the Crouzon syndrome mutations in a severe Pfeiffer syndrome type 2 case. Am J Med Genet 75:252–255. https://doi.org/10.1002/(sici)1096-8628(19980123)75:3%3c252::aid-ajmg4%3e3.0.co;2-s

  35. Shetye PR, Boutros S, Grayson BH, McCarthy JG (2007) Midterm follow-up of midface distraction for syndromic craniosynostosis: a clinical and cephalometric study. Plast Reconstr Surg 120:1621–1632. https://doi.org/10.1097/01.prs.0000267422.37907.6f

    Article  CAS  PubMed  Google Scholar 

  36. Swanson JW, Samra F, Bauder A, Mitchell BT, Taylor JA, Bartlett SP (2016) An algorithm for managing syndromic craniosynostosis using posterior vault distraction osteogenesis. Plast Reconstr Surg 137:829e–841e. https://doi.org/10.1097/PRS.0000000000002127

    Article  CAS  PubMed  Google Scholar 

  37. Tartaglia M, Valeri S, Velardi F, Di Rocco C, Battaglia PA (1997) Trp290Cys mutation in exon IIIa of the fibroblast growth factor receptor 2 (FGFR2) gene is associated with Pfeiffer syndrome. Hum Genet 99:602–606. https://doi.org/10.1007/s004390050413

    Article  CAS  PubMed  Google Scholar 

  38. Tartaglia M, Di Rocco C, Lajeunie E, Valeri S, Velardi F, Battaglia PA (1997) Jackson-Weiss syndrome: identification of two novel FGFR2 missense mutations shared with Crouzon and Pfeiffer craniosynostotic disorders. Hum Genet 101:47–50. https://doi.org/10.1007/s004390050584

    Article  CAS  PubMed  Google Scholar 

  39. Taylor JA, Bartlett SP (2017) What’s new in syndromic craniosynostosis surgery? Plast Reconstr Surg 140:82e–93e. https://doi.org/10.1097/PRS.0000000000003524

    Article  CAS  PubMed  Google Scholar 

  40. Thomas GP, Wall SA, Jayamohan J, Magdum SA, Richards PG, Wiberg A, Johnson D (2014) Lessons learned in posterior cranial vault distraction. J Craniofac Surg 25:1721–1727. https://doi.org/10.1097/SCS.0000000000000995

    Article  PubMed  Google Scholar 

  41. White N, Evans M, Dover MS, Noons P, Solanki G, Nishikawa H (2009) Posterior calvarial vault expansion using distraction osteogenesis. Childs Nerv Syst 25:231–236. https://doi.org/10.1007/s00381-008-0758-6

    Article  PubMed  Google Scholar 

  42. Wiberg A, Magdum S, Richards PG, Jayamohan J, Wall SA, Johnson D (2012) Posterior calvarial distraction in craniosynostosis - an evolving technique. J Craniomaxillofac Surg 40:799–806. https://doi.org/10.1016/j.jcms.2012.02.018

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Plastic and Craniofacial Surgery, SOBRAPAR Hospital, Av. Adolpho Lutz, 100, Caixa Postal: 6028, Campinas, São Paulo, 13084-880, Brazil

    Cassio Eduardo Raposo-Amaral, Yuri Moresco Oliveira, Rafael Denadai, Cesar Augusto Raposo-Amaral & Enrico Ghizoni

  2. Department of Neurology, University of Campinas (UNICAMP), São Paulo, Brazil

    Cassio Eduardo Raposo-Amaral & Enrico Ghizoni

Authors
  1. Cassio Eduardo Raposo-Amaral
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuri Moresco Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rafael Denadai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cesar Augusto Raposo-Amaral
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Enrico Ghizoni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Cassio Eduardo Raposo-Amaral.

Ethics declarations

Conflict of interest

The authors have no personal financial or institutional interest in any of the drugs, materials, or devices described in this article.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Raposo-Amaral, C.E., Oliveira, Y.M., Denadai, R. et al. Severe craniolacunae and upper and lower extremity anomalies resulting from Crouzon syndrome, FGFR2 mutation, and Ser347Cys variant. Childs Nerv Syst 37, 2391–2397 (2021). https://doi.org/10.1007/s00381-020-04993-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00381-020-04993-w

Keywords

Search

Navigation