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

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

Author information

1
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA.
2
1] Department of Human Genetics, University of Leuven, Leuven, Belgium [2] Center for Human Genetics, Leuven University Hospitals, Leuven, Belgium.
3
Medical Genomics Laboratory, Department of Genetics, University of Alabama at Birmingham, Alabama, USA.
4
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
5
Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
6
Division of Medical Genetics, Department of Pediatrics A.I. duPont Hospital for Children, Wilmington, Delaware, USA.
7
Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
8
Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA.
9
Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida, USA.
10
Genetics Unit, MassGeneral Hospital for Children, Boston, Massachusetts, USA.
11
1] Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA [2] Department of Medical Genetics, Duke University Medical Center, Durham, North Carolina, USA.
12
1] Department of Medical Genetics, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada [2] Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
13
Children's Hospital of Wisconsin, Milwaukee, Wisconsin, USA.
14
Department of Orthopedic Surgery, University Hospitals Leuven, Leuven, Belgium.
15
Greenwood Genetic Center, Greenwood, South Carolina, USA.
16
Medical Genetics/Metabolism, Children's Hospital Central California, Madera, California, USA.
17
Children's Hospitals and Clinics of Minnesota, Department of Genetics, Minneapolis, Minnesota, USA.
18
Division of Medical Genetics, Massachusetts General Hospital, Boston, Massachusetts, USA.
19
Department of Clinical Genetics, Academic Medical Centre, Amsterdam, The Netherlands.
20
LewisGale Regional Health System, Department of Clinical Genetics, Salem, Virginia, USA.

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.

PMID:
24232412
DOI:
10.1038/gim.2013.163
[Indexed for MEDLINE]

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