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Acta Otorhinolaryngologica Italica :... Oct 2016Neurofibromatosis type 2 [NF2; MIM # 101000] is an autosomal dominant disorder characterised by the occurrence of vestibular schwannomas (VSs), schwannomas of other... (Review)
Review
Neurofibromatosis type 2 [NF2; MIM # 101000] is an autosomal dominant disorder characterised by the occurrence of vestibular schwannomas (VSs), schwannomas of other cranial, spinal and cutaneous nerves, cranial and spinal meningiomas and/or other central nervous system (CNS) tumours (e.g., ependymomas, astrocytomas). Additional features include early onset cataracts, optic nerve sheath meningiomas, retinal hamartomas, dermal schwannomas (i.e., NF2-plaques), and (few) café-au-lait spots. Clinically, NF2 children fall into two main groups: (1) congenital NF2 - with bilateral VSs detected as early as the first days to months of life, which can be stable/asymptomatic for one-two decades and suddenly progress; and (2) severe pre-pubertal (Wishart type) NF2- with multiple (and rapidly progressive) CNS tumours other-than-VS, which usually present first, years before VSs [vs. the classical adult (Gardner type) NF2, with bilateral VSs presenting in young adulthood, sometimes as the only disease feature]. Some individuals can develop unilateral VS associated with ipsilateral meningiomas or multiple schwannomas localised to one part of the peripheral nervous system [i.e., mosaic NF2] or multiple non-VS, non-intradermal cranial, spinal and peripheral schwannomas (histologically proven) [schwannomatosis]. NF2 is caused by mutations in the NF2 gene at chromosome 22q12.1, which encodes for a protein called merlin or schwannomin, most similar to the exrin-readixin-moesin (ERM) proteins; mosaicNF2 is due to mosaic phenomena for the NF2 gene, whilst schwannomatosis is caused by coupled germ-line and mosaic mutations either in the SMARCB1 gene [SWNTS1; MIM # 162091] or the LZTR1 gene [SWNTS2; MIM # 615670] both falling within the 22q region and the NF2 gene. Data driven from in vitro and animal studies on the merlin pathway [e.g., post-translational and upstream/downstream regulation] allowed biologically targeted treatment strategies [e.g., Lapatinib, Erlotinib, Bevacizumab] aimed to multiple tumour shrinkage and/or regression and tumour arrest of progression with functional improvement.
Topics: Biological Therapy; Child; Humans; Neurofibromatosis 2
PubMed: 27958595
DOI: 10.14639/0392-100X-1093 -
British Journal of Anaesthesia Apr 2001The neurofibromatoses are autosomal dominant diseases that have widespread effects on ectodermal and mesodermal tissue. The commonest member of the group is... (Review)
Review
The neurofibromatoses are autosomal dominant diseases that have widespread effects on ectodermal and mesodermal tissue. The commonest member of the group is neurofibromatosis type 1 (NF1) which varies in severity but which can affect all physiological systems. Neurofibromas are the characteristic lesions of the condition and not only occur in the neuraxis but may also be found in the oropharnyx and larynx; these may produce difficulties with laryngoscopy and tracheal intubation. Pulmonary pathology includes pulmonary fibrosis and cystic lung disease. The cardiovascular manifestations of NF1 include hypertension, which may be associated with phaeochromocytoma or renal artery stenosis. Neurofibromas may also affect the gastrointestinal tract and carcinoid tumours may be found in the duodenum. This review documents the aetiology and clinical manifestations of the neurofibromatoses and discusses their relevance to the anaesthetist.
Topics: Anesthesia; Humans; Neurofibromatoses; Neurofibromatosis 1; Neurofibromatosis 2
PubMed: 11573632
DOI: 10.1093/bja/86.4.555 -
Developmental Medicine and Child... Nov 2017Over the past several decades, neurofibromatosis type 1 (NF1) has become increasingly recognized as a neurodevelopmental disorder conferring increased risk for several... (Review)
Review
Over the past several decades, neurofibromatosis type 1 (NF1) has become increasingly recognized as a neurodevelopmental disorder conferring increased risk for several important neurodevelopmental problems. In this review, we summarize the specific neurodevelopmental problems encountered in the context of NF1. These include impairments in general cognitive function, deficits in specific cognitive domains such as executive function and visuospatial processing and risk for specific learning disorders, impairments in attention and social skills and the overlap with attention-deficit-hyperactivity disorder and autism spectrum disorder, and the risk of developing other psychiatric conditions including anxiety and depression. Early recognition of these developmental impairments is important for the effective treatment of children with NF1, and further characterization is essential to improve our understanding of how mutations in the NF1 gene create the diversity of clinical neuropsychiatric symptomatology observed in this at-risk population.
Topics: Child; Humans; Neurodevelopmental Disorders; Neurofibromatosis 1
PubMed: 28845518
DOI: 10.1111/dmcn.13526 -
Journal of Neuro-oncology Sep 2022Peripheral and intraspinal schwannomas are common and clinically complex pathologies in patients with Neurofibromatosis Type 2 (NF2) and Schwannomatosis (SWNT).... (Observational Study)
Observational Study
INTRODUCTION
Peripheral and intraspinal schwannomas are common and clinically complex pathologies in patients with Neurofibromatosis Type 2 (NF2) and Schwannomatosis (SWNT). Functional preservation and pain relief are the major goals in treating these tumors.
METHODS
This retrospective observational study investigates the clinical and functional outcome of 205 operated peripheral (n = 148, 72%) and intraspinal (n = 57, 28%) schwannomas in 85 patients (53 NF2, 32 SWNT) treated at our department between 2006 and 2017. Associated factors such as genetics, age, and location were evaluated.
RESULTS
Persisting drug-resistant pain was the most common symptom (84%, n = 173) and indication for surgery (54%, n = 110). Improvement in pain intensity was postoperatively seen in 81%. Peripheral nerve schwannomas exhibited worse pain intensity preoperatively compared to intraspinal lesions (p = 0.017 NF2, p = 0.029 SWNT). More total resections could be achieved in 93% of SWNT vs. 82% of NF2-associated tumors, p = 0.030). NF2 patients with intraspinal lesions were more neurologically affected (p < 0.05). Perioperative comparison of both tumor syndromes showed more neurological deficits (p = 0.027), and less pain (p = 0.024) in NF2-associated tumors. Mosaic NF2 patients had worse pain levels before surgery, and SWNT patients had a worse neurological function and more pain compared to non-mosaic or non-mutated cases.
CONCLUSIONS
Resection of peripheral and intraspinal schwannomas is an effective and low-risk treatment in both NF2 and SWNT. Patients with severe pain have a particular benefit from surgical treatment. Intraspinal lesions are associated with worse neurological function whereas peripheral lesions showed a higher pain intensity. The influence of mutations needs to be further investigated in larger cohorts.
Topics: Humans; Neurilemmoma; Neurofibromatoses; Neurofibromatosis 2; Pain; Skin Neoplasms
PubMed: 35771312
DOI: 10.1007/s11060-022-04061-0 -
Expert Opinion on Investigational Drugs Apr 2013The neurofibromatoses (neurofibromatosis type 1, NF1 and neurofibromatosis type 2, NF2) comprise the most common inherited conditions in which affected children and... (Review)
Review
INTRODUCTION
The neurofibromatoses (neurofibromatosis type 1, NF1 and neurofibromatosis type 2, NF2) comprise the most common inherited conditions in which affected children and adults develop tumors of the central and peripheral nervous system. In this review, the authors discuss how the establishment of the Neurofibromatosis Clinical Trials Consortium (NFCTC) has positively impacted on the design and execution of treatment studies for individuals with NF1 and NF2.
AREAS COVERED
Using an extensive PUBMED search in collaboration with select NFCTC members expert in distinct NF topics, the authors discuss the clinical features of NF1 and NF2, the molecular biology of the NF1 and NF2 genes, the development and application of clinically relevant Nf1 and Nf2 genetically engineered mouse models and the formation of the NFCTC to enable efficient clinical trial design and execution.
EXPERT OPINION
The NFCTC has resulted in a more seamless integration of mouse preclinical and human clinical trials efforts. Leveraging emerging enabling resources, current research is focused on identifying subtypes of tumors in NF1 and NF2 to deliver the most active compounds to the patients most likely to respond to the targeted therapy.
Topics: Animals; Antineoplastic Agents; Clinical Trials as Topic; Humans; Neurofibromatosis 1; Neurofibromatosis 2; Neurofibromin 1; Neurofibromin 2; United States
PubMed: 23425047
DOI: 10.1517/13543784.2013.772979 -
The Journal of Neuroscience : the... Oct 2012Brain development in neurodevelopmental disorders has been considered to comprise a sequence of critical periods, and abnormalities occurring during early development... (Review)
Review
Brain development in neurodevelopmental disorders has been considered to comprise a sequence of critical periods, and abnormalities occurring during early development have been considered irreversible in adulthood. However, findings in mouse models of neurodevelopmental disorders, including fragile X, Rett syndrome, Down syndrome, and neurofibromatosis type I suggest that it is possible to reverse certain molecular, electrophysiological, and behavioral deficits associated with these disorders in adults by genetic or pharmacological manipulations. Furthermore, recent studies have suggested that critical period-like plasticity can be reactivated in the adult brain by environmental manipulations or by pharmacotherapy. These studies open up a tantalizing possibility that targeted pharmacological treatments in combination with regimes of training or rehabilitation might alleviate or reverse the symptoms of neurodevelopmental disorders even after the end of critical developmental periods. Even though translation from animal experimentation to clinical practice is challenging, these results suggest a rational basis for treatment of neurodevelopmental disorders in adulthood.
Topics: Adult; Age Factors; Animals; Developmental Disabilities; Fragile X Syndrome; Genetic Therapy; Humans; Nervous System Diseases; Neurofibromatoses; Neuronal Plasticity; Treatment Outcome
PubMed: 23055475
DOI: 10.1523/JNEUROSCI.3287-12.2012 -
Hematology/oncology Clinics of North... Oct 2010In this article hereditary genodermatoses with cancer predisposition are reviewed, including nevoid basal cell carcinoma syndrome, neurofibromatosis types 1 and 2,... (Review)
Review
In this article hereditary genodermatoses with cancer predisposition are reviewed, including nevoid basal cell carcinoma syndrome, neurofibromatosis types 1 and 2, tuberous sclerosis complex, xeroderma pigmentosum, and dyskeratosis congenita. Hereditary melanoma is also included, though it differs from the others in several respects. The underlying genetic aberrations causing these syndromes are largely known, allowing novel treatments to be developed for some of these disorders. Early recognition and diagnosis allows for close follow-up and surveillance for associated malignancies.
Topics: Animals; Basal Cell Nevus Syndrome; Genetic Predisposition to Disease; Genetic Testing; Humans; Melanoma; Neoplastic Syndromes, Hereditary; Neurofibromatoses; Skin Diseases; Xeroderma Pigmentosum
PubMed: 20816579
DOI: 10.1016/j.hoc.2010.06.003 -
Neurology Nov 2013The neurofibromatoses (NF)--including neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis--are related tumor-suppressor syndromes characterized by... (Review)
Review
The neurofibromatoses (NF)--including neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis--are related tumor-suppressor syndromes characterized by a predisposition to multiple tumor types and other disease manifestations, which often result in functional disability, reduced quality of life, pain, and, in some cases, malignancy. With increasing knowledge of the biology and pathogenesis of NF, clinical trials with targeted agents directed at NF tumors have become available. Most clinical trials for patients with NF have used designs and endpoints similar to oncology trials. However, differences in the disease manifestations and natural history of NF (compared to cancers) require the development of new designs and endpoints to perform meaningful NF clinical trials. The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration was established in 2011 at the Children's Tumor Foundation meeting to achieve consensus within the NF community about the design of future clinical trials, with a specific emphasis on endpoints. The REiNS Collaboration includes 7 working groups that focus on imaging of tumor response; functional, visual, patient-reported, and neurocognitive outcomes; whole-body MRI; and disease biomarkers. This supplement includes the first series of recommendations by the REiNS Collaboration. The hope is that these recommendations will be used by members of the group and by researchers outside of the REiNS International Collaboration to standardize the measurement of outcomes and thus improve clinical trials for patients with NF. Ultimately, we plan to engage industry partners and national regulatory agencies in this process to facilitate the approval of drugs for patients with NF.
Topics: Clinical Trials as Topic; Consensus; Humans; Neurofibromatoses
PubMed: 24249801
DOI: 10.1212/01.wnl.0000435743.49414.b6 -
BMJ Case Reports Jun 2018
Topics: Child; Clitoris; Female; Humans; Hypertrophy; Neurofibromatoses; Testosterone
PubMed: 29903778
DOI: 10.1136/bcr-2018-225350 -
Arquivos de Neuro-psiquiatria Jun 2015Part 1 of this guideline addressed the differential diagnosis of the neurofibromatoses (NF): neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and...
Part 1 of this guideline addressed the differential diagnosis of the neurofibromatoses (NF): neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis (SCH). NF shares some features such as the genetic origin of the neural tumors and cutaneous manifestations, and affects nearly 80 thousand Brazilians. Increasing scientific knowledge on NF has allowed better clinical management and reduced rate of complications and morbidity, resulting in higher quality of life for NF patients. Most medical doctors are able to perform NF diagnosis, but the wide range of clinical manifestations and the inability to predict the onset or severity of new features, consequences, or complications make NF management a real clinical challenge, requiring the support of different specialists for proper treatment and genetic counseling, especially in NF2 and SCH. The present text suggests guidelines for the clinical management of NF, with emphasis on NF1.
Topics: Disease Management; Humans; Neurilemmoma; Neurofibromatoses; Neurofibromatosis 1; Neurofibromatosis 2; Optic Nerve Glioma; Risk Factors; Skin Neoplasms
PubMed: 26083891
DOI: 10.1590/0004-282X20150042