Neurofibromatosis 1 (Neurofibromatosis Type I)

An autosomal dominant inherited disorder (with a high frequency of spontaneous mutations) that features developmental changes in the nervous system, muscles, bones, and skin, most notably in tissue derived from the embryonic NEURAL CREST. Multiple hyperpigmented skin lesions and subcutaneous tumors are the hallmark of this disease. Peripheral and central nervous system neoplasms occur frequently, especially OPTIC NERVE GLIOMA and NEUROFIBROSARCOMA. NF1 is caused by mutations which inactivate the NF1 gene (GENES, NEUROFIBROMATOSIS 1) on chromosome 17q. The incidence of learning disabilities is also elevated in this condition. (From Adams et al., Principles of Neurology, 6th ed, pp1014-18) There is overlap of clinical features with NOONAN SYNDROME in a syndrome called neurofibromatosis-Noonan syndrome. Both the PTPN11 and NF1 gene products are involved in the SIGNAL TRANSDUCTION pathway of Ras (RAS PROTEINS).

Also Known As:

Networked: 586 relevant articles (5 outcomes, 38 trials/studies) for this Disease, Comments

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Hearing Loss (Hearing Impairment)
2.	Pseudarthrosis (Pseudoarthrosis)
3.	Neoplasms (Cancer)
4.	Plexiform Neurofibroma
5.	Nerve Sheath Neoplasms (Nerve Sheath Neoplasm)

Experts

1.	Gutmann, David H: 10 articles (08/2009 - 08/2002)
2.	Parada, Luis F: 8 articles (11/2009 - 02/2007)
3.	Peltonen, Juha: 6 articles (06/2005 - 03/2002)
4.	Koivunen, Jussi: 6 articles (06/2005 - 03/2002)
5.	Gutmann, D H: 5 articles (11/2009 - 09/2000)
6.	Ratner, Nancy: 5 articles (07/2009 - 01/2004)
7.	Saya, Hideyuki: 5 articles (04/2008 - 03/2003)
8.	Araki, Norie: 5 articles (04/2008 - 03/2003)
9.	Ylä-Outinen, Heli: 5 articles (06/2005 - 03/2002)
10.	Wolkenstein, P: 4 articles (07/2009 - 11/2001)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Neurofibromatosis 1:

1.	Neurofibromin 1 (Neurofibromin)IBA 01/01/2009 - "In the past several years, significant progress has been made in standardizing management of the major clinical features of neurofibromatosis type 1. Moreover, improved understanding of how the neurofibromatosis type 1 protein, neurofibromin, regulates cell growth recently provided insight into the pathogenesis of the disease and has led to the development of new therapies. " 03/01/2010 - "Neurofibromatosis type 1 (NF1) results from mutations in the NF1 tumor suppressor gene, which encodes the protein neurofibromin. " 01/01/2010 - "Neurofibromatosis Type 1 is caused by germline mutations of the NF1 tumor suppressor gene, which generally result in decreased intracellular neurofibromin protein levels, leading to increased cascade Ras signaling to its downstream effectors. " 05/01/2009 - "The protein giant neurofibromin (320kDa) is the protein product of the NF1 tumor suppressor gene, alterations of which are responsible for the pathogenesis of neurofibromatosis type 1 (NF1). " 12/01/2008 - "Neurofibromatosis type 1 (NF1) is a common genetic disorder caused by mutations in the NF1 locus, which encodes neurofibromin, a negative regulator of Ras. " Order ALL the reference details at left...
2.	Cholecalciferol (Vitamin D3)FDA Link 04/01/1999 - "Topical application of vitamin D3 analogues for 6 months was found to be effective in improving the pigmentation of café au lait spots in patients with von Recklinghausen's disease. " 04/01/1999 - "Vitamin D3 analogues improve café au lait spots in patients with von Recklinghausen's disease: experimental and clinical studies." 04/01/2007 - "Treatment of pigmented lesions of neurofibromatosis 1 with intense pulsed-radio frequency in combination with topical application of vitamin D3 ointment." 04/01/1999 - "Thus, it is considered that long-term application of vitamin D3 analogues is effective both for improving the pigmentation of café au lait spots and suppressing the development of neurofibromas in patients with von Recklinghausen's disease." Order ALL the reference details at left...
3.	Lovastatin (Mevacor)FDA LinkGeneric 11/08/2005 - "Therefore, these results demonstrate that lovastatin may prove useful in the treatment of Neurofibromatosis Type 1." 01/01/2008 - "Modelling neurofibromatosis type 1 tibial dysplasia and its treatment with lovastatin." 07/01/2008 - "Induction of apoptosis in neurofibromatosis type 1 malignant peripheral nerve sheath tumor cell lines by a combination of novel farnesyl transferase inhibitors and lovastatin." 11/08/2005 - "The HMG-CoA reductase inhibitor lovastatin reverses the learning and attention deficits in a mouse model of neurofibromatosis type 1." Order ALL the reference details at left...
4.	Bone Morphogenetic Proteins (Bone Morphogenetic Protein)IBA 01/01/2008 - "Recombinant bone morphogenetic proteins (BMPs) show promise in treating the orthopedic complications associated with neurofibromatosis type 1 (NF1), such as congenital pseudarthrosis of the tibia. " Order ALL the reference details at left...
5.	Genetic Markers (Genetic Marker)IBA 10/05/1991 - "[Neurofibromatosis Type 1: genetic studies with DNA markers in 38 families]" 05/01/1991 - "Linkage analysis of neurofibromatosis type 1. Study of a homogeneous North Italian population with five DNA markers of chromosome 17." 12/01/1987 - "Relationships among genetic markers in the region of the neurofibromatosis type 1 (NF1) gene on chromosome 17 were investigated by linkage studies in a large sample set of affected families and in a panel of 58 normal families. " 12/01/1987 - "Linkage studies with chromosome 17 DNA markers in 45 neurofibromatosis 1 families." 05/01/1992 - "Genetic linkage of neurofibromatosis 1 to the NF1 gene or the genetic marker in the pericentric region of chromosome 17 was established in 3 informative families." Order ALL the reference details at left...
6.	DNA (Deoxyribonucleic Acid)IBA 01/01/1989 - "Fine structure DNA mapping studies of the chromosomal region harboring the genetic defect in neurofibromatosis type I." 08/01/2002 - "This is also reflected in the lack of a simple, inexpensive, highly accurate DNA-based test for neurofibromatosis 1 at present. " 02/01/2000 - "A total of 196 unrelated patients with neurofibromatosis type 1 (NF1) was screened for mutations in exons 4a-c of the NF1 gene by temperature gradient gel electrophoresis (TGGE) of polymerase chain reaction (PCR)-amplified genomic DNA fragments using intron-based primers. " 10/01/1999 - "The neurofibromatosis type 1 (NF1) gene located at 17q 11.2 contains 60 exons and spans 350 kb of genomic DNA. " 06/12/1997 - "We detected the same mutation in DNA from the affected parent of each child with familial neurofibromatosis type 1. CONCLUSIONS: Both alleles of the NF1 gene are inactivated in leukemic cells in some patients with neurofibromatosis type 1. NF1 appears to function as a tumor-suppressor gene in immature myeloid cells." Order ALL the reference details at left...
7.	Succinate Dehydrogenase (Fumarate Reductase)IBA 10/01/2008 - "The inherited predisposition may be attributable to a germline mutation in the Von Hippel-Lindau gene, the genes encoding the subunits B and D of succinate dehydrogenase, the RET proto-oncogene predisposing to multiple endocrine neoplasia type 2, or the neurofibromatosis type 1 gene. " 05/01/2009 - "Succinate dehydrogenase and Von-Hippel Lindau-related tumors had a significantly higher SUVmax than did neurofibromatosis type 1 and multiple endocrine neoplasia type 2A syndrome-related tumors (P = 0.02). " 12/01/2007 - "Most PHEOs are sporadic, but a significant percentage (approximately 25%) may be found in patients with germline mutations of genes predisposing to the development of von Hippel-Lindau disease, neurofibromatosis 1, multiple endocrine neoplasia type 1 (MEN1) and 2 (MEN2), and the PGL/PHEOs syndrome, based on the described mutations of the genes for succinate dehydrogenase subunit D (SDHD), B (SDHB), and C (SDHC). " 01/01/2006 - "von Hippel-Lindau disease, succinate dehydrogenase subunit mutations, multiple endocrine neoplasia type 2 and neurofibromatosis type 1) is important because of the opportunity to reduce morbidity and mortality from phaeochromocytoma and other relevant tumours in affected individuals and their at-risk relatives. " 03/01/2005 - "Phaeochromocytoma is a neural-crest-derived tumour that may be a feature of several familial cancer syndromes including von Hippel-Lindau (VHL) disease, multiple endocrine neoplasia type 2 (MEN 2), neurofibromatosis type 1 (NF1) and germline succinate dehydrogenase subunit (SDHB and SDHD) mutations. " Order ALL the reference details at left...
8.	Protons (Proton)IBA 11/01/2003 - "To determine whether differences exist between neurofibromatosis type 1 (NF1) patients with or without focal lesions and healthy normal volunteers in the metabolite ratios of normal appearing white matter, 27 patients with NF1 (with parenchymal lesion, MR positive, n: 17; without parenchymal lesions, MR negative, n: 10) and 20 healthy volunteers underwent MRI and short TE (31 ms) proton MR spectroscopy (MRS). " 11/01/2003 - "Proton MR spectroscopy features of normal appearing white matter in neurofibromatosis type 1." 10/01/2001 - "Proton magnetic resonance spectroscopy of brain lesions in children with neurofibromatosis type 1." 04/01/2000 - "Thalamic involvement in neurofibromatosis type 1: evaluation with proton magnetic resonance spectroscopic imaging." 11/01/1999 - "Short TE proton MRS and neurofibromatosis type 1 intracranial lesions." Order ALL the reference details at left...
9.	Growth Hormone (Somatotropin)IBA 05/01/2000 - "Growth hormone deficiency in children with neurofibromatosis type 1 without suprasellar lesions." 08/01/1998 - "Growth hormone in von Recklinghausen's disease: reckless or recommended?" 02/01/2008 - "CONCLUSION: This study suggests that growth hormone may influence the development of plexiform neurofibromas in patients with neurofibromatosis type 1." 08/01/2003 - "Examples of associated diagnoses included neurofibromatosis Type 1 (5.5%), hydrocephalus (11%), idiopathic growth hormone deficiency (5.5%), and Klippel-Feil anomaly (5%). " 01/01/2000 - "We report a girl with neurofibromatosis type 1, an extensive optic nerve glioma and growth hormone hypersecretion. " Order ALL the reference details at left...
10.	HormonesIBA 11/18/1961 - "[The action of sexual hormones in a case of von Recklinghausen's disease.]" 07/01/2007 - "In vitro studies of steroid hormones in neurofibromatosis 1 tumors and Schwann cells." 02/01/2008 - "INTRODUCTION: The development of multiple neurofibromas is one of the major features of neurofibromatosis type 1. Since neurofibromas commonly grow during periods of hormonal change, especially during puberty and pregnancy, it has been suggested that hormones may influence neurofibromatosis type 1 neurofibromas. " 06/01/2003 - "Adult height of patients given GH or gonadotropin hormone-releasing hormone analogue seems to depend on neurofibromatosis 1." 01/01/2009 - "In recent years, germline mutations that affect components of the RAS-MAPK (mitogen-activated protein kinase) pathway were shown to be involved in the pathogenesis of NS and four rare syndromes with clinical features overlapping with NS: Leopard syndrome, cardio-facio-cutaneous syndrome, Costello syndrome and neurofibromatosis type 1. Several hormones act through receptors that stimulate the RAS-MAPK pathway, and therefore, NS and related disorders represent a remarkable opportunity to study the implication of the RAS-MAPK pathway in different endocrine systems. " Order ALL the reference details at left...

Therapies and Procedures

1.	Cochlear Implantation 09/01/2003 - "OBJECTIVE: To determine the efficacy of cochlear implantation in an individual with neurofibromatosis type 1 and profound hearing loss and to determine, to the extent possible in a living subject, the site of lesion of the hearing loss in an individual with neurofibromatosis type 1. STUDY DESIGN: Postoperative assessment of an adult male with neurofibromatosis type 1. SETTING: The study was completed in the Departments of Otolaryngology and Audiology, University of Massachusetts Medical Center, Massachusetts. " 09/01/2003 - "Based on the results of this investigation, standard cochlear implantation should be considered a viable option and the first line of therapy for the treatment of bilateral, severe to profound sensorineural hearing loss in patients with neurofibromatosis type 1 and normal, VIIIth nerve radiographic findings." 09/01/2003 - "Cochlear implantation in a patient with neurofibromatosis type 1 and profound hearing loss: evidence to support a cochlear site of lesion." 09/01/2003 - "CONCLUSIONS: This is the first case report describing the outcome of cochlear implantation in a patient with neurofibromatosis type 1. Composite test results support the absence of VIIIth nerve degeneration or other anomalies, indicating a cochlear site of lesion for the hearing loss in this patient. " Order ALL the reference details at left...
2.	Radiotherapy 06/01/2008 - "Four patients had undergone previous radiotherapy, and 2 had neurofibromatosis Type 1. Five cases of MTT were lumbosacral, 4 were thoracic, and 1 was cervical. " 03/01/1999 - "The major risk factor was neurofibromatosis type 1. Radiotherapy should no longer be the first treatment in these settings. " 07/01/1998 - "Our studies showed that relapse-free survival improves with increasing age, the presence of neurofibromatosis 1 (NF1), and chemotherapy and radiotherapy (p < 0.0005). " 01/01/1995 - "Based on an analysis of a limited number of cases, ours and those collected from the literature (21 patients), some suggestions are possible: a) pre-operative clinical presentation and imaging studies are not predictive of malignancy; b) postoperative outcome is poor, especially in patients with von Recklinghausen's disease and after partial removal of the tumour; c) local recurrence and metastases are possible, even after radical surgery and radiotherapy." 10/01/2006 - "RECENT FINDINGS: Important papers regarding optic-pathway gliomas have been published recently in the following areas: neuroimaging, natural history and how the presence of neurofibromatosis type 1 affects it, unusual presentations, visual prognosis, and treatment with fractionated stereotactic radiotherapy. " Order ALL the reference details at left...
3.	Laminectomy 01/15/1998 - "STUDY DESIGN: A case of a 9-year-old girl with von Recklinghausen's disease who has acute tetraparesis caused by a complete dislocation of C6-C7 after a cervical laminectomy performed at another hospital. " 09/01/2009 - "We report a 58-year-old patient with known neurofibromatosis Type 1 (NF-1) who presented with an aggressive recurrent malignant peripheral nerve sheath tumour and spinal cord compression 5 weeks after undergoing tumour excision with thoracic (T)6-7 laminectomy. " 09/01/2003 - "STUDY DESIGN: A case report of a child with quadriplegia as a result of neurofibromatosis type I who had cervical laminectomy for spinal cord decompression followed by occipitocervical instrumentation is described. " 09/01/2003 - "CONCLUSIONS: The reported case emphasizes the need for treating acute neurologic symptoms caused by spinal cord compression in neurofibromatosis type I as well as addressing the future risk of spinal deformity following laminectomy." 12/01/2001 - "More frequently they are the consequence of spinal instability as in neurofibromatosis (von Recklinghausen's disease), after laminectomies, in tumors, congenital disorders, spondylodiscitis, and fractures. " Order ALL the reference details at left...
4.	Drug Therapy (Chemotherapy) 07/01/1998 - "Our studies showed that relapse-free survival improves with increasing age, the presence of neurofibromatosis 1 (NF1), and chemotherapy and radiotherapy (p < 0.0005). " 05/01/2003 - "We report a new case of demodicidosis in a 22-month-old girl undergoing chemotherapy for chronic myelomonocytic leukaemia associated with xanthoma and type 1 neurofibromatosis. " 08/01/2009 - "Sixty-seven patients had documented or presumed WHO grade 1 tumors, 25 patients had prior chemotherapy, and 13 patients had neurofibromatosis type 1. RESULTS: During a median follow-up of 89 months, 13 patients experienced disease progression. " 02/01/2009 - "Although both chemotherapy and radiotherapy can stabilize and sometimes improve vision in progressive tumours, chemotherapy is the preferred modality in children younger than 9 years and in patients with neurofibromatosis 1. In functionally progressive optic nerve meningioma with useful visual function, multifractioned stereotactic conformal radiotherapy is the treatment of choice." 01/01/2000 - "Growth hormone hypersecretion in a girl with neurofibromatosis type 1 and an optic nerve glioma: resolution following chemotherapy." Order ALL the reference details at left...
5.	Decompression 06/01/1991 - "A patient with a basilar impression accompanied by a Chiari malformation and von Recklinghausen's disease who underwent transoral decompression is reported. " 09/01/2003 - "STUDY DESIGN: A case report of a child with quadriplegia as a result of neurofibromatosis type I who had cervical laminectomy for spinal cord decompression followed by occipitocervical instrumentation is described. " Order ALL the reference details at left...