Neurofibromatosis type 1 is a disorder of dysplasia: The importance of distinguishing features, consequences, and complications

✍ Scribed by Vincent Michael Riccardi

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 94 KB
• Volume: 88
• Category: Article
• ISSN: 1542-0752
• DOI: 10.1002/bdra.20616

✦ Synopsis

Abstract

BACKGROUND: The disorder neurofibromatosis type 1 (NF1) is caused by mutations in the NF1 gene, which influences the availability of activated Ras and the latter's control of cellular proliferation. Emphasis on this aspect of NF1 has focused attention on the tumor suppression function of NF1 and thereby displaced attention from the gene's role in initial normal tissue formation, maintenance, and repair. METHODS: Clinical and neuroimaging data systematically compiled over more than 30 years are analyzed to document the involvement of multiple organs and tissues, often with an embryonic origin. In addition, recent literature based on selective knockout mouse experiments is cited to corroborate embryonic dysplasia as an element of NF1 pathogenesis. RESULTS: Tissue dysplasia, both ab initio and as part of tissue maintenance and wound healing, is a key clinical and pathogenetic aspect of NF1 and thereby provides a rationale for differentiating the elements of NF1 into features, consequences, and complications. CONCLUSIONS: NF1 is a histogenesis control gene that also has properties that overlap with those of a tumor suppressor gene. Both its neoplastic and dysplastic manifestations become more amenable to understanding and treatment if they are differentiated at three levels—specifically, features, consequences and complications. Birth Defects Research (Part A), 2010. © 2009 Wiley‐Liss, Inc.