neurofibromatosis Dotaz Zobrazit nápovědu
Neurofibromatosis von Recklinghausen type 1 (NF1) is a multisystem, autosomal dominant hereditary neurocutaneous disease characterized by skin, central and peripheral nervous system , eyes , bone, endocrine, gastrointestinal and blood vessel wall involvement. It has an estimated frequency of 1 in 3000. Neurofibromatosis type 1 is caused by mutations in the large NF1 gene located on chromosome 17q11.2, encoding the cytoplasmic protein neurofibromin. It is expressed in multiple cell types but is highly expressed in Schwann cells, oligodendrocytes, neurons, astrocytes and leukocytes. Neurofibromin is known to act as a tumor suppressor via Ras-GTPase activation, which causes down-regulation of cellular signaling via the Ras/mitogen-activated protein kinase (MAPK) pathway. Failure of this function is associated with a tendency to form tumors which are histologically hamartomas as well as benign tumors. Tumors of the central nervous system include low-grade gliomas (pilocytic astrocytomas grade I), especially optic pathway gliomas. They are often clinically asymptomatic. Other intracranial tumors are in the brain stem and also elsewhere in the brain and spinal cord. Hydrocephalus may be a complication of NF1 gliomas or due to stenosis of the distal part of the aqueduct Silvii. Cutaneous and subcutaneous neurofibromas or plexiform neurofibromas are localized in the peripheral nervous system. Plexiform neurofibromas have a significant lifetime risk of malignancy. The clinical diagnosis of NF1 is defined by diagnostic criteria. The NF1 diagnosis is satisfied when at least two of the seven conditions are met. The method of direct DNA analysis of large NF1 gene (61 exons) is available. The results of studies of genotype - phenotype established few correlations. But predicting the disease by finding mutations is not currently possible. NF1 exhibits a wide range of variability of expression and complete penetrance, even within the same family. About half of cases are new mutations. The treatment of patients with neurofibromatosis is symptomatic. Central nervous system symptomatic low-grade gliomas are most often treated with chemotherapy. For plexiform neurofibromas surgical removal is currently the only treatment option.
PURPOSE: Evaluate the effectiveness of treatment of patients with optic pathway glioma. MATERIALS AND METHODS: Comparison of literature research on neurofibromatosis and optic pathway glioma with a cohort of pediatric patients treated at the Childrens Ophthalmology Clinic of the University Hospital in Brno from January 2013 until June 2018. DISCUSSION: The main challenge of this and other retrospective studies is variable intervals between ophthalmologic examinations. In some pediatric patients it is also difficult to objectively assess visual functions. The main risk factors are age at the time of treatment and tumor localization. Tumor progression itself does not always correlate with worse visual acuity outcomes, and it remains to be evaluated whether some patients would be better off without treatment. As of now, there are no clinical biomarkers able to predict impending visual acuity loss. CONCLUSION: The cohort outcome agrees with literature. Chemotherapy remains a treatment of choice and its most likely outcome is visual acuity stabilization. In order to properly evaluate the treatments effectiveness, better collaboration between medical specialists and regular standardized ophthalmology examinations are required.
- Klíčová slova
- chemotherapy, children, neurofibromatosis, optic pathway glioma, treatment,
- MeSH
- dítě MeSH
- gliom zrakového nervu terapie MeSH
- lidé MeSH
- neurofibromatóza 1 terapie MeSH
- poruchy zraku MeSH
- retrospektivní studie MeSH
- zraková ostrost MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- EYES *, NEUROFIBROMATOSIS *,
- MeSH
- lidé MeSH
- neurofibromatóza 1 * MeSH
- neurofibromatózy * MeSH
- oči * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
AIM: To clarify the possibilities and role of posterior segment imaging in patients with neurofibromatosis type I (NF1), and to show the prevalence of this disease in the pediatric population in Slovakia. MATERIAL AND METHODS: Until recently, ophthalmologic consultations in patients with NF1 were limited mainly to the observation of Lisch nodules of the iris and the presence of optic nerve glioma. However, advances in imaging capabilities have made it possible to investigate and describe new f indings concerning the ocular manifestations of this disease. Between October 2020 and November 2021, we examined the anterior and posterior segment of 76 eyes (38 children – 12 boys and 26 girls) with genetically confirmed NF1 gene mutation at our clinic. The age of the patients ranged from 4 to 18 years. The anterior segment was checked for the presence of Lisch nodules biomicroscopically with a slit lamp. On the posterior segment, the presence of choroidal nodules was checked by various imaging methods – fundus camera, infrared confocal selective laser ophthalmoscopy, MultiColor imaging, OCT, and OCT angiography. All the patients had magnetic resonance imaging performed in order to detect potential optic nerve gliomas for the purpose of diagnosis. We observed the correlation between the patients’ age, presence of Lisch nodules and the presence of choroidal nodules. Eight patients also had other manifestations of the disease – optic nerve gliomas or microvascular changes (so-called “corkscrew” vessels). RESULTS: Out of 38 patients, Lisch iris nodules were present in 20 patients (53%) and choroidal nodules in 24 patients (63%). There was no positive correlation between the presence of these two manifestations within the same patient or eye, but there is a clear correlation between the presence of choroidal nodules and patient age. CONCLUSION: The results suggest that a previously unknown ocular manifestation of neurofibromatosis type I, namely choroidal nodules, has a higher prevalence than Lisch nodules also in the pediatric population and can be easily visualized using various imaging modalities. It will be important to include follow-up observation of this finding among the standard controls for ocular findings in NF1, and it will be very interesting to correlate this f inding with the exact NF1 mutation
- Klíčová slova
- neurofibromatosis type 1, von Recklinghausen’s disease, choroidea, choroidal nodules, imaging modalities,
- MeSH
- choroidea patologie MeSH
- dítě MeSH
- gliom zrakového nervu * MeSH
- lidé MeSH
- mladiství MeSH
- multimodální zobrazování MeSH
- neurofibromatóza 1 * komplikace MeSH
- oftalmoskopie metody MeSH
- předškolní dítě MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Neurofibromatosis type 2 (NF-2) is a dominantly inherited genetic disorder that results from variants in the tumor suppressor gene, neurofibromin 2 (NF2). Here, we report the generation of a conditional zebrafish model of neurofibromatosis established by inducible genetic knockout of nf2a/b, the zebrafish homologs of human NF2. Analysis of nf2a and nf2b expression revealed ubiquitous expression of nf2b in the early embryo, with overlapping expression in the neural crest and its derivatives and in the cranial mesenchyme. In contrast, nf2a displayed lower expression levels. Induction of nf2a/b knockout at early stages increased the proliferation of larval Schwann cells and meningeal fibroblasts. Subsequently, in adult zebrafish, nf2a/b knockout triggered the development of a spectrum of tumors, including vestibular Schwannomas, spinal Schwannomas, meningiomas and retinal hamartomas, mirroring the tumor manifestations observed in patients with NF-2. Collectively, these findings highlight the generation of a novel zebrafish model that mimics the complexities of the human NF-2 disorder. Consequently, this model holds significant potential for facilitating therapeutic screening and elucidating key driver genes implicated in NF-2 onset.
- Klíčová slova
- Cancer, Inducible knockout, Meninges, Neurofibromatosis type 2, Schwann cells, Zebrafish,
- MeSH
- dánio pruhované * genetika embryologie MeSH
- geneticky modifikovaná zvířata MeSH
- genový knockout * MeSH
- larva metabolismus MeSH
- lidé MeSH
- modely nemocí na zvířatech * MeSH
- neurofibromatóza 2 genetika patologie metabolismus MeSH
- neurofibromatózy genetika patologie metabolismus MeSH
- neurofibromin 2 * genetika metabolismus nedostatek MeSH
- proliferace buněk MeSH
- proteiny dánia pruhovaného * genetika metabolismus nedostatek MeSH
- Schwannovy buňky metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- neurofibromin 2 * MeSH
- proteiny dánia pruhovaného * MeSH
- MeSH
- hlava * MeSH
- lidé MeSH
- nádory obličeje MeSH
- neurofibromatóza 1 * diagnóza MeSH
- prognóza MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The authors performed HLA typing in 18 patients affected by neurofibromatosis (NF) and in 13 of them they also typed all the available members of their families. In 9 families manifesting a kindred occurrence further 16 patients, in whom the disease had not yet been diagnosed, have been unveiled. In 8 families our of nine manifesting a familial load of the disease there was agreement in one HLA haplotype eventually HLA identity among the diseased sibling members. From this point of view it appears that HLA typing in NF might be a valuable contribution especially for the diagnosis of the complete cases in families manifesting a kindred type of NF occurrence. Since NF is a disease perilous through its life endangering complications of a malignant character the authors recommend its dispensation and a concentration of all the NF affected patients and their relatives into a limited number of clinical establishments endowed with a possibility of cooperation with some HLA laboratory.
- MeSH
- dítě MeSH
- dospělí MeSH
- HLA antigeny analýza genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- neurofibromatóza 1 genetika imunologie MeSH
- předškolní dítě MeSH
- rodokmen MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- HLA antigeny MeSH
A simultaneous finding of pseudoangiomatous stromal hyperplasia (PASH) and stromal multinucleated giant cells (MGC) in mammary tissue was previously observed in patients with type-1 neurofibromatosis, indicating that it can represent a morphologic marker for this syndrome. Here, we present PASH with MGC occurring in the left breast of a 39-years-old woman who does not have neurofibromatosis. This case, along with two additional ones reported previously, indicates that PASH with MGC in the female breast may not be associated with neurofibromatosis.
- MeSH
- angiomatóza komplikace diagnóza patologie MeSH
- biologické markery analýza MeSH
- dospělí MeSH
- hyperplazie komplikace diagnóza patologie MeSH
- lidé MeSH
- nemoci prsů komplikace diagnóza patologie MeSH
- neurofibromatóza 1 komplikace MeSH
- prsy patologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- biologické markery MeSH
A case of an accidental finding of neurofibromatosis 2 in a practically asymptomatic patient is described. Various therapeutic modalities, including restoration of hearing after vestibular schwannoma surgery with an auditory brainstem implant (ABI), are considered.
- MeSH
- dospělí MeSH
- lidé MeSH
- neurofibromatóza 2 chirurgie MeSH
- sluchové kmenové implantáty * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
