Jaffe-Campanacci syndrome, revisited: Detailed clinical and molecular analyses determine whether patients have neurofibromatosis type 1, coincidental manifestations, or a distinct disorder

Douglas R. Stewart, Hilde Brems, Alicia G. Gomes, Sarah L. Ruppert, Tom Callens, Jennifer Williams, Kathleen Claes, Michael B. Bober, Rachel Hachen, Leonard B. Kaban, Hua Li, Angela Lin, Marie McDonald, Serge Melancon, June Ortenberg, Heather B. Radtke, Ignace Samson, Robert A. Saul, Joseph Shen, Elizabeth SiqvelandTomi L. Toler, Merel Van Maarle, Margaret Wallace, Misti Williams, Eric Legius, Ludwine Messiaen

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Purpose:"Jaffe-Campanacci syndrome" describes the complex of multiple nonossifying fibromas of the long bones, mandibular giant cell lesions, and café-au-lait macules in individuals without neurofibromas. We sought to determine whether Jaffe-Campanacci syndrome is a distinct genetic entity or a variant of neurofibromatosis type 1.Methods:We performed germline NF1, SPRED1, and GNAS1 (exon 8) mutation testing on patients with Jaffe-Campanacci syndrome or Jaffe-Campanacci syndrome-related features. We also performed somatic NF1 mutation testing on nonossifying fibromas and giant cell lesions.Results: Pathogenic germline NF1 mutations were identified in 13 of 14 patients with multiple café-au-lait macules and multiple nonossifying fibromas or giant cell lesions ("classical" Jaffe-Campanacci syndrome); all 13 also fulfilled the National Institutes of Health diagnostic criteria for neurofibromatosis type 1. Somatic NF1 mutations were detected in two giant cell lesions but not in two nonossifying fibromas. No SPRED1 or GNAS1 (exon 8) mutations were detected in the seven NF1-negative patients with Jaffe-Campanacci syndrome, nonossifying fibromas, or giant cell lesions.Conclusion:In this study, the majority of patients with café-au-lait macules and nonossifying fibromas or giant cell lesions harbored a pathogenic germline NF1 mutation, suggesting that many Jaffe-Campanacci syndrome cases may actually have neurofibromatosis type 1. We provide the first proof of specific somatic second-hit mutations affecting NF1 in two giant cell lesions from two unrelated patients, establishing these as neurofibromatosis type 1-associated tumors.Genet Med 16 6, 448-459.

Original languageEnglish
Pages (from-to)448-459
Number of pages12
JournalGenetics in Medicine
Volume16
Issue number6
DOIs
StatePublished - Jun 2014

Keywords

  • Jaffe-Campanacci syndrome
  • café-au-lait macule
  • giant cell lesion
  • neurofibromatosis type 1
  • nonossifying fibroma

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