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

Genet Med. 2014 Jun;16(6):448-59. doi: 10.1038/gim.2013.163. Epub 2013 Nov 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adolescent
  • Adult
  • Bone Neoplasms / genetics
  • Cafe-au-Lait Spots / genetics*
  • Cafe-au-Lait Spots / pathology
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Chromogranins
  • Female
  • Fibroma / genetics
  • GTP-Binding Protein alpha Subunits, Gs / genetics*
  • Germ-Line Mutation
  • Humans
  • Infant
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Membrane Proteins / genetics*
  • Neurofibromatosis 1 / diagnosis
  • Neurofibromatosis 1 / genetics*
  • Neurofibromatosis 1 / pathology
  • Neurofibromin 1 / genetics*
  • Sex Ratio
  • Young Adult


  • Adaptor Proteins, Signal Transducing
  • Chromogranins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Neurofibromin 1
  • SPRED1 protein, human
  • GNAS protein, human
  • GTP-Binding Protein alpha Subunits, Gs