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: 1078 relevant articles (9 outcomes, 61 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Neurofibroma
2.	Hearing Loss (Hearing Impairment)
3.	Pseudarthrosis (Pseudoarthrosis)
4.	Ganglion Cysts (Ganglion)
5.	Plexiform Neurofibroma

Experts

1.	Gutmann, David H: 17 articles (08/2015 - 08/2002)
2.	Plotkin, Scott R: 12 articles (03/2015 - 01/2009)
3.	Mautner, Victor F: 12 articles (01/2015 - 11/2005)
4.	Ratner, Nancy: 10 articles (10/2015 - 01/2004)
5.	Parada, Luis F: 10 articles (01/2015 - 02/2007)
6.	Widemann, Brigitte C: 9 articles (06/2015 - 01/2006)
7.	Peltonen, Juha: 9 articles (01/2015 - 03/2002)
8.	Wolkenstein, Pierre: 8 articles (01/2015 - 12/2003)
9.	Dombi, Eva: 7 articles (10/2015 - 05/2007)
10.	Pacak, Karel: 7 articles (04/2015 - 06/2005)

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. " 12/01/2015 - "In mouse, we found that inactivation of neurofibromin 1 (Nf1), a gene mutated in neurofibromatosis type 1, unlocked a latent oligodendrocyte lineage potential to produce all three lineages from NSCs in vivo. " 10/01/2015 - "Arg(1809) substitution in neurofibromin: further evidence of a genotype-phenotype correlation in neurofibromatosis type 1." 08/15/2015 - "Neurofibromatosis type 1 (NF1) is a common neurodevelopmental disorder caused by impaired function of the neurofibromin RAS regulator. " 01/01/2015 - "Neurofibromin - protein structure and cellular functions in the context of neurofibromatosis type I pathogenesis."
2.	Fluorodeoxyglucose F18 (Fludeoxyglucose F 18)FDA Link 02/01/2014 - "18F-FDG PET/CT for detection of malignant peripheral nerve sheath tumours in neurofibromatosis type 1: tumour-to-liver ratio is superior to an SUVmax cut-off." 03/01/2015 - "18F-FDG PET/CT qualitative and quantitative evaluation in neurofibromatosis type 1 patients for detection of malignant transformation: comparison of early to delayed imaging with and without liver activity normalization." 01/01/2014 - "Utility of 18F-FDG PET with a semi-quantitative index in the detection of sarcomatous transformation in patients with neurofibromatosis type 1." 01/01/2012 - "To systematically review the role of positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (FDG) in patients with neurofibromatosis type 1 (NF1). " 01/01/2012 - "Usefulness of whole-body fluorine-18-fluorodeoxyglucose positron emission tomography in patients with neurofibromatosis type 1: a systematic review."
3.	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. " 05/01/2013 - "Effect of vitamin D3 treatment on bone density in neurofibromatosis 1 patients: a retrospective clinical study." 04/01/1999 - "Vitamin D3 analogues improve café au lait spots in patients with von Recklinghausen's disease: experimental and clinical studies." 05/01/2013 - "We have previously demonstrated reduced bone density and an increased incidence of 25-hydroxy vitamin D3 (25-OH D3) deficiency in adults with neurofibromatosis 1 (NF1) compared to healthy controls. " 04/01/2007 - "Treatment of pigmented lesions of neurofibromatosis 1 with intense pulsed-radio frequency in combination with topical application of vitamin D3 ointment."
4.	Retinaldehyde (Retinal)IBA 01/01/2014 - "This study describes distinctive retinal microvascular alterations and their relationship to choroidal nodules in patients with neurofibromatosis type 1. This was a retrospective study where records of seventeen consecutive patients with diagnosis of NF1, presenting Lisch nodules and choroidal alterations, and 17 age and gender-matched healthy control patients were evaluated. " 06/01/2015 - "Morphologic and vasculature features of the choroid and associated choroid-retinal thickness alterations in neurofibromatosis type 1." 01/01/2014 - "Retinal microvascular abnormalities overlying choroidal nodules in neurofibromatosis type 1." 04/01/2013 - "To report the clinical findings and outcomes in 3 patients with neurofibromatosis 1 (NF1) and retinal vascular abnormalities that resulted in angle closure secondary to iris neovascularization and describe the histopathologic abnormalities in 1 case. " 01/01/2013 - "Here, we report a case of retinal microvascular abnormalities in a patient with neurofibromatosis type 1 (NF1) associated with congenital retinal macrovessels. "
5.	Lovastatin (Mevacor)FDA LinkGeneric 11/08/2005 - "Therefore, these results demonstrate that lovastatin may prove useful in the treatment of Neurofibromatosis Type 1." 10/01/2011 - "These observations may be analogous to the improvements observed in a neurofibromatosis type 1 murine model treated with lovastatin, although further study and replication are required. " 10/01/2011 - "We report on a phase I study examining the safety and tolerability of lovastatin in children with neurofibromatosis type 1. Twenty-four children with neurofibromatosis type 1 underwent a dose-escalation protocol for 3 months to identify the maximum tolerated dose and potential toxicity. " 10/01/2011 - "Lovastatin as treatment for neurocognitive deficits in neurofibromatosis type 1: phase I study." 01/01/2013 - "Lovastatin improves impaired synaptic plasticity and phasic alertness in patients with neurofibromatosis type 1."
6.	Carbon DioxideIBA 01/01/2015 - "Few studies have evaluated the efficacy of carbon dioxide (CO2) laser ablation for treating neurofibromatosis type 1 (NF1). "
7.	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. "
8.	VitaminsIBA 10/01/2013 - "Narrowband ultraviolet B irradiation increases the serum level of vitamin D₃ in patients with neurofibromatosis 1." 10/01/2013 - "It is suggested that NB-UVB irradiation is effective for increasing the serum level of vitamin D₃ in patients with neurofibromatosis 1, which may be of benefit for skin symptoms such as pigmented macules or neurofibromas." 10/01/2013 - "The serum vitamin D₃ levels in patients with neurofibromatosis 1 has been reported to be significantly lower than that in control subjects, and the level of vitamin D₃ reversely correlates with the severity of neurofibroma formation. " 10/01/2013 - "We found that narrowband ultraviolet B (NB-UVB) irradiation increased the serum level of 1,25(OH)₂ vitamin D₃ in patients with neurofibromatosis 1. The difference in the 1,25(OH)₂ vitamin D₃ levels between patients who had received irradiation for more than 18 months and those who had no irradiation was highly significant. "
9.	Succinate Dehydrogenase (Fumarate Reductase)IBA 01/01/2014 - "Recent studies of these so-called wild-type GISTs have uncovered a number of other oncogenic drivers, including mutations in neurofibromatosis type I, RAS genes, BRAF, and subunits of the succinate dehydrogenase complex. " 01/01/2015 - "The description of new genes linked to familial forms of PCC/PGLs, such as succinate dehydrogenase (SDH) complex subunits, KIF1Bβ, EGLN1, TMEM127, and MAX, added to the well-known PCC familial syndrome (MEN2, VHL, and neurofibromatosis type 1) presents new challenges for diagnosis. " 01/01/2014 - "The molecular biology of these GIST, originally defined as KIT/PDGFRA wild-type (WT), is complex due to the existence of different subgroups with distinct molecular hallmarks, including defects in the succinate dehydrogenase (SDH) complex and mutations of neurofibromatosis type 1 (NF1), BRAF, or KRAS genes (RAS-pathway or RAS-P).In this extremely heterogeneous landscape, the clinical profile and molecular abnormalities of the small subgroup of WT GIST suitably referred to as quadruple wild-type GIST (quadrupleWT or KITWT/PDGFRAWT/SDHWT/RAS-PWT) remains undefined. " 09/01/2012 - "We assessed succinate dehydrogenase complex subunit B (SDHB) and IGF1R expression by immunohistochemistry in eight known succinate dehydrogenase-deficient GISTs, three GISTs arising in the setting of neurofibromatosis type 1 syndrome and 40 unselected GISTs. " 02/01/2014 - "Three syndromic conditions-Von Hippel-Lindau (vhl), multiple endocrine neoplasia type 2 (men2), and neurofibromatosis type 1 (nf1)-and three genes-subunits of the succinate dehydrogenase (SDH) complex: SDHB, SDHC, and SDHD-are established causes of hereditary pheo-pgl. "
10.	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."

Therapies and Procedures

1.	Gas Lasers 11/11/2000 - "[CO2-laser therapy of stigmatizing cutaneous lesions in tuberous sclerosis (Bourneville-Pringle) and in neurofibromatosis 1 (von Recklinghausen)]." 01/01/2015 - "Few studies have evaluated the efficacy of carbon dioxide (CO2) laser ablation for treating neurofibromatosis type 1 (NF1). " 06/01/1991 - "The CO2 laser is presented as a useful tool for the removal of large numbers of neurofibromas, the major source of cosmetic disfigurement in the patient with peripheral neurofibromatosis. "
2.	Cochlear Implantation 04/01/2015 - "Successful cochlear implantation in two profoundly deafened patients with neurofibromatosis type 1: further evidence to support a cochlear site of lesion." 09/01/2003 - "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. Postoperative assessment of an adult male with neurofibromatosis type 1. The study was completed in the Departments of Otolaryngology and Audiology, University of Massachusetts Medical Center, Massachusetts. " 04/01/2015 - "To investigate the usefulness of cochlear implantation and to examine the evidence for a cochlear or retrocochlear site of lesion for deafness in Neurofibromatosis Type 1 (NF1). " 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."
3.	Radiotherapy 07/01/2013 - "If manifests itself more often in individuals with neurofibromatosis type I (NF-1) disease but also sporadically or post 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). " 06/01/2011 - "A rare complication is cerebral vasculopathy, which occurs most often in patients with neurofibromatosis type 1. Interstitial radiotherapy using transient Iodine-125 implants is a radiotherapy option, called brachytherapy, offering excellent survival rates, but little is known on treatment-related morbidity, especially long time vascular changes. "
4.	Drug Therapy (Chemotherapy) 08/01/2014 - "Pharmacotherapy of attention deficit in neurofibromatosis type 1: effects on cognition." 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). " 01/01/2013 - "Chemotherapy for the treatment of malignant peripheral nerve sheath tumors in neurofibromatosis 1: a 10-year institutional review." 09/15/2012 - "Patients with neurofibromatosis type 1 (NF1) develop malignant peripheral nerve sheath tumors (MPNST), which are often inoperable and do not respond well to current chemotherapies or radiation. " 03/01/2011 - "MPNST associated to neurofibromatosis type 1 was the tumour type with the worst rate of response to chemotherapy and the worst outcome. "
5.	Transplants (Transplant) 01/01/2008 - "In this report, we describe a novel surgical technique, combining computer-aided design, stereolithography and neuronavigation to repair a temporal base skull defect in a 16-year-old female patient with neurofibromatosis type 1. A three-dimensional model of the skull base defect and a template for graft were first constructed according to the image data, then transferred to a real-size stereolithographic biomodel using a rapid prototyping technique. " 02/01/2005 - "To our knowledge, the case presented here is the first to describe successful surgical management--graft replacement of the left subclavian artery--in hemothorax due to arterial dissection associated with von Recklinghausen's disease." 12/01/2004 - "Asymptomatic massive dural ectasia associated with neurofibromatosis type 1 threatening spinal column support: treatment by anterior vascularized fibula graft." 01/01/2013 - "Clinical outcomes of combined anterior and posterior spinal fusion for dystrophic thoracolumbar spinal deformities of neurofibromatosis-1: fate of nonvascularized anterior fibular strut grafts." 12/01/2005 - "We report a case of congenital pseudarthrosis of the forearm associated with neurofibromatosis type 1 which was treated by free vascularized periosteal flap transplant and repeated bone grafting. "