TY - JOUR
T1 - Jaffe-Campanacci syndrome, revisited
T2 - Detailed clinical and molecular analyses determine whether patients have neurofibromatosis type 1, coincidental manifestations, or a distinct disorder
AU - Stewart, Douglas R.
AU - Brems, Hilde
AU - Gomes, Alicia G.
AU - Ruppert, Sarah L.
AU - Callens, Tom
AU - Williams, Jennifer
AU - Claes, Kathleen
AU - Bober, Michael B.
AU - Hachen, Rachel
AU - Kaban, Leonard B.
AU - Li, Hua
AU - Lin, Angela
AU - McDonald, Marie
AU - Melancon, Serge
AU - Ortenberg, June
AU - Radtke, Heather B.
AU - Samson, Ignace
AU - Saul, Robert A.
AU - Shen, Joseph
AU - Siqveland, Elizabeth
AU - Toler, Tomi L.
AU - Van Maarle, Merel
AU - Wallace, Margaret
AU - Williams, Misti
AU - Legius, Eric
AU - Messiaen, Ludwine
PY - 2014/6
Y1 - 2014/6
N2 - 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.
AB - 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.
KW - Jaffe-Campanacci syndrome
KW - café-au-lait macule
KW - giant cell lesion
KW - neurofibromatosis type 1
KW - nonossifying fibroma
UR - http://www.scopus.com/inward/record.url?scp=84902083515&partnerID=8YFLogxK
U2 - 10.1038/gim.2013.163
DO - 10.1038/gim.2013.163
M3 - Article
C2 - 24232412
AN - SCOPUS:84902083515
SN - 1098-3600
VL - 16
SP - 448
EP - 459
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 6
ER -