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Neurofibromatosis presenting with a cherubism phenotype

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Abstract

We report on a child who presented clinical manifestations of both neurofibromatosis type 1 (NF1) and cherubism. With genetic testing, we found a mutation in the NF-1 gene, confirming the neurocutaneous disorder. Histology when correlated with radiological evaluation of a mandibular biopsy was consistent with cherubism. This is the first report in the literature of a child with proven neurofibromatosis type 1 and cherubism without extragnathic lesions. This emphasises that cherubism is a clinical phenotype that can be associated with a number of germline mutations involving SH3BP2, PTPN11 and NF1.

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References

  1. Addante RR, Breen GH (1996) Cherubism in a patient with Noonan’s syndrome. J Oral Maxillofac Surg 54:210–213

    Article  PubMed  CAS  Google Scholar 

  2. Ardekian L, Manor R, Peled M, Laufer D (1999) Bilateral central giant cell granulomas in a patient with neurofibromatosis : report of a case and review of the literature. J Oral Maxillofac Surg 57(7):869–872

    Article  PubMed  CAS  Google Scholar 

  3. Ayoub AF, El-Mofty SS (1993) Cherubism: report of an aggressive case and review of the literature. J Oral Maxillofac Surg 51:702–705

    Article  PubMed  CAS  Google Scholar 

  4. Buehning L, Curry CJ (1995) Neurofibromatosis-Noonan syndrome. Pediatr Dermatol 12:267–271

    PubMed  CAS  Google Scholar 

  5. Cohen MM Jr, Gorlin RJ (1991) Noonan-like/multiple giant cell lesion syndrome. Am J Med Genet 40:159–166

    Article  PubMed  Google Scholar 

  6. Colby RS, Saul RA (2003) Is Jaffe-Campanacci syndrome just a manifestation of neurofibromatosis type 1? Am J Med Genet 123(1):60–63

    Article  Google Scholar 

  7. DeBella K, Szudek J, Friedman JM (2000) Use of the national institutes of health criteria for diagnosis of neurofibromatosis 1 in children. Pediatrics 105(3 Pt 1):608–614

    Article  PubMed  CAS  Google Scholar 

  8. De Lange J, van den Akker HP (2005) Clinical and radiological features of central giant-cell lesions of the jaw. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 99(4):464–470

    Article  PubMed  Google Scholar 

  9. DeTomasi DC, Hann JR, Stewart HM Jr (1985) Cherubism, report of a nonfamilial case. J Am Dent Assoc 111(3):455–457

    PubMed  CAS  Google Scholar 

  10. Dunlap C, Neville B, Vickers RA, O’Neil D, Barker B (1989) The Noonan syndrome/cherubism association. Oral Surg Oral Med Oral Pathol 67(6):698–705

    Article  PubMed  CAS  Google Scholar 

  11. Fahsold R, Hoffmeyer S, Mischung C, Gille C, Ehlers C, Kucukceylan N, Abdel-Nour M, Gewies A, Peters H, Kaufmann D, Buske A, Tinschert S, Nurnberg P (2000) Minor lesion mutational spectrum of the entire NF1 gene does not explain its high mutability but points to a functional domain upstream of the GAP-related domain. Am J Hum Genet 66:790–818

    Article  PubMed  CAS  Google Scholar 

  12. Han SS, Cooper DN, Upadhyaya MN (2001) Evaluation of denaturing high performance liquid chromatography (DHPLC) for the mutational analysis of the neurofibromatosis type 1 (NF1) gene. Hum Genet 109:487–497

    Article  PubMed  CAS  Google Scholar 

  13. Jafarov T, Ferimazova N, Reichenberger E (2005) Noonan-like syndrome mutations in PTPN11 in patients diagnosed with cherubism. Clin Genet 68:190–191

    Article  PubMed  CAS  Google Scholar 

  14. Kaugars GE, Niamtu J III, Svirsky JA (1992) Cherubism: diagnosis, treatment and comparison with central giant cell granulomas and giant cell tumors. Oral Surg Oral Med Oral Pathol 73:369–374

    Article  PubMed  CAS  Google Scholar 

  15. Krammer U, Wimmer K, Wiesbauer P, Rasse M, Lang S, Mullner-Eidenbock A, Frisch H (2003) Neurofibromatosis 1: a novel NF1 mutation in an 11-year-old girl with a giant cell granuloma. J Child Neurol 18(5):371–373

    Article  PubMed  Google Scholar 

  16. Li CY, Yu SF (2006) Mutation detection in SH3BP2 gene in a cherubism family. Zhonghua Kou Qiang Yi Xue Za Zhi 41:368–371

    PubMed  CAS  Google Scholar 

  17. Lietman SA, Kalinchinko N, Deng X, Kohanski R, Levine MA (2006) Identification of a novel mutation of SH3BP2 in cherubism and demonstration that SH3BP2 mutations lead to increased NFAT activation. Hum Mutat 27:717–718

    Article  PubMed  Google Scholar 

  18. Lo B, Faiyaz-Ul-Haque M, Kennedy S, Aviv R, Tsui LC, Teebi AS (2003) Novel mutation in the gene encoding c-Abl-binding protein SH3BP2 causes cherubism. Am J Med Genetics 121:37–40

    Article  Google Scholar 

  19. Imai Y, Kanno K, Moriya T, Kayano S, Seino H, Matsubara Y, Yamada A (2003) A missense mutation in the SH3BP2 gene on chromosome 4p16.3 found in a case of nonfamilial cherubism. Cleft Palate Craniofac J 40:632–638

    Article  PubMed  Google Scholar 

  20. Mangion J, Rahman N, Edkins S, Barfoot R, Nguyen T, Sigurdsson A, Townend JV, Fitzpatrick DR, Flanagan AM, Stratton MR (1999) The gene for cherubism maps to chromosome 4p16.3. Am J Hum Genet 65(1):151–157

    Article  PubMed  CAS  Google Scholar 

  21. Martinez-Tello FJ, Manjon-Luengo P, Martinez-Perez M, Montes-Moreno S (2005) Cherubism associated with neurofibromatosis type 1, and multiple osteolytic lesions of both femurs: a previously undescribed association of findings. Skeletal Radiol 34(12):793–798

    Article  PubMed  Google Scholar 

  22. Mirra JM, Gold RH, Rand F (1982) Disseminated nonossifying fibromas in association with café-au-lait spots (Jaffe-Campanacci syndrome). Clin Orthop Relat Res (168):192–205

    PubMed  Google Scholar 

  23. Neurofibromatosis. Conference statement. National Institutes of Health Consensus Development Conference (1988) Arch Neurol 45(5):575–578

    Google Scholar 

  24. Ruggieri M, Pavone V, Polizzi A, Albanese S, Magro G, Merino M, Duray PH (1999) Unusual form of recurrent giant cell granuloma of the mandible and lower extremities in a patient with neurofibromatosis type 1. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 87:67–72

    Article  PubMed  CAS  Google Scholar 

  25. Sarkozy A, Obregon MG, Conti E, Esposito G, Mingarelli R, Pizzuti A, Dallapiccola B (2004) A Novel PTPN11 gene mutation bridges Noonan syndrome, multiple lentigines/LEOPARD syndrome and Noonan-like/multiple giant cell lesion syndrome. Eur J Hum Genet 12:1069–1072

    Article  PubMed  CAS  Google Scholar 

  26. Shen MH, Harper PS, Upadhyaya M (1996) Molecular genetics of neurofibromatosis type 1 (NF1). J Med Genet 33(1):2–17

    Article  PubMed  CAS  Google Scholar 

  27. Southgate J, Sarma U, Townend JV, Barron J, Flanagan AM (1998) Study of the cell biology and biochemistry of cherubism. J Clin Pathol 51(11):831–837

    PubMed  CAS  Google Scholar 

  28. Ueki Y, Tiziani V, Santanna C, Fukai N, Maulik C, Garfinkle J, Ninomiya C, doAmaral C, Peters H, Habal M, Rhee-Morris L, Doss JB, Kreiborg S, Olsen BR, Reichenberger E (2001) Mutations in the gene encoding c-Abl-binding protein SH3BP2 cause cherubism. Nat Genet 28:125–126

    Article  PubMed  CAS  Google Scholar 

  29. Van Damme PA, Mooren RE (1994) Differentiation of multiple giant cell lesions, Noonan-like syndrome, and (occult) hyperparathyroidism. Case report and review of the literature. Int J Oral Maxillofac Surg 23(1):32–36

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, Meander Medisch Centrum, P.O. Box 1502, 3800BM, Amersfoort, The Netherlands

    C. I. van Capelle & P. H. G. Hogeman

  2. Division of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands

    C. J. M. van der Sijs-Bos

  3. Department of Radiology, Meander Medisch Centrum, Amersfoort, The Netherlands

    B. G. F. Heggelman

  4. Institute of Orthopaedics and Musculoskeletal Science, University College London, London, UK

    B. Idowu & A. M. Flanagan

  5. Department of Pathology, University Medical Center Radboud, Nijmegen, The Netherlands

    P. J. Slootweg

  6. Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands

    P. J. Slootweg

  7. Department of Oral-Maxillofacial Surgery, Meander Medisch Centrum, Amersfoort, The Netherlands

    A. R. M. Wittkampf

  8. Department of Oral-Maxillofacial Surgery, University Medical Center Utrecht, Utrecht, The Netherlands

    A. R. M. Wittkampf

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  1. C. I. van Capelle
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  2. P. H. G. Hogeman
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  3. C. J. M. van der Sijs-Bos
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  4. B. G. F. Heggelman
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  5. B. Idowu
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  6. P. J. Slootweg
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  7. A. R. M. Wittkampf
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  8. A. M. Flanagan
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Correspondence to P. H. G. Hogeman.

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van Capelle, C.I., Hogeman, P.H.G., van der Sijs-Bos, C.J.M. et al. Neurofibromatosis presenting with a cherubism phenotype. Eur J Pediatr 166, 905–909 (2007). https://doi.org/10.1007/s00431-006-0334-6

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  • DOI: https://doi.org/10.1007/s00431-006-0334-6

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