RESUMO
Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disorder characterized by proliferation of cells from neural crest origin. The most common manifestations are cutaneous, neurologic, skeletal and ocular. The distinction of NF1 from other syndromes with multiple café-au-lait macules may be difficult in the pediatric age group, and ocular findings, especially Lisch nodules (i.e., melanocytic hamartomas on the irides), are a useful, early diagnostic tool. In recent years, novel ocular manifestations descriptively referred to as "choroidal abnormalities", choroidal "hyperpigmented spots" and "retinal vascular abnormalities" have been recognized in NF1. Choroidal abnormalities (CA) appear as bright patchy nodules that can be best detected with near-infrared ocular coherence tomography imaging (NIR-OCT). Because of their high specificity and sensitivity for NF1, CA have been added as an ocular diagnostic criterion of NF1 as an alternative to Lisch nodules. Although CA are important ocular diagnostic criteria for NF1, the histologic correlates are controversial. We present the postmortem ocular pathology findings of an NF1 patient for whom clinical notes and ocular imaging were available. Findings in this patient included choroidal hyperpigmented spots on funduscopy and retinal vascular abnormalities, both of which have been reported to be closely associated with CA. Histologic examination of the eyes showed multiple clusters of melanocytes of varying sizes in the choroid. Pathologic review of 12 additional postmortem eyes from 6 NF1 patients showed multiple, bilateral choroidal melanocytic aggregates in all eyes. These findings suggest that the CA seen on NIR-OCT and the hyperpigmented spots seen clinically in NF1 patients are manifestations of multifocal choroidal melanocytic clusters, consistent with choroidal melanocytic hamartomas. Lisch nodules, often multiple, were present in all eyes with morphology that differed from the choroidal hamartomas. As such, although CA and Lisch nodules are melanocytic hamartomas, there are clear phenotypical differences in their morphologies.
Assuntos
Hamartoma , Neurofibromatose 1 , Humanos , Criança , Neurofibromatose 1/complicações , Corioide/diagnóstico por imagem , AutopsiaRESUMO
BACKGROUND/AIMS: Individuals with neurofibromatosis 1 may experience changes in their appearance due to physical manifestations of the disorders and/or treatment sequelae. Appearance concerns related to these physical changes can lead to psychological distress and poorer quality of life. While many neurofibromatosis 1 clinical trials focus on assessing changes in tumor volume, evaluating patients' perspectives on corresponding changes in symptoms such as physical appearance can be key secondary outcomes. We aimed to determine whether any existing patient-reported outcome measures are appropriate for evaluating changes in appearance concerns within neurofibromatosis 1 clinical trials. METHODS: After updating our previously published systematic review process, we used it to identify and rate existing patient-reported outcome measures related to disfigurement and appearance. Using a systematic literature search and initial triage process, we focused on identifying patient-reported outcome measures that could be used to evaluate changes in appearance concerns in plexiform or cutaneous neurofibroma clinical trials in neurofibromatosis 1. Our revised Patient-Reported Outcome Rating and Acceptance Tool for Endpoints then was used to evaluate each published patient-reported outcome measures in five domains, including (1) respondent characteristics, (2) content validity, (3) scoring format and interpretability, (4) psychometric data, and (5) feasibility. The highest-rated patient-reported outcome measures were then re-reviewed in a side-by-side comparison to generate a final consensus recommendation. RESULTS: Eleven measures assessing appearance concerns were reviewed and rated; no measures were explicitly designed to assess appearance concerns related to neurofibromatosis 1. The FACE-Q Craniofacial Module-Appearance Distress scale was the top-rated measure for potential use in neurofibromatosis 1 clinical trials. Strengths of the measure included that it was rigorously developed, included individuals with neurofibromatosis 1 in the validation sample, was applicable to children and adults, covered item topics deemed important by neurofibromatosis 1 patient representatives, exhibited good psychometric properties, and was feasible for use in neurofibromatosis 1 trials. Limitations included a lack of validation in older adults, no published information regarding sensitivity to change in clinical trials, and limited availability in languages other than English. CONCLUSION: The Response Evaluation in Neurofibromatosis and Schwannomatosis patient-reported outcome working group currently recommends the FACE-Q Craniofacial Module Appearance Distress scale to evaluate patient-reported changes in appearance concerns in clinical trials for neurofibromatosis 1-related plexiform or cutaneous neurofibromas. Additional research is needed to validate this measure in people with neurofibromatosis 1, including older adults and those with tumors in various body locations, and explore the effects of nontumor manifestations on appearance concerns in people with neurofibromatosis 1 and schwannomatosis.
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Neurilemoma , Neurofibroma Plexiforme , Neurofibromatoses , Neurofibromatose 1 , Neoplasias Cutâneas , Criança , Humanos , Idoso , Neurofibromatose 1/complicações , Neurofibromatose 1/tratamento farmacológico , Neurofibroma Plexiforme/complicações , Neurofibroma Plexiforme/diagnóstico , Neurofibroma Plexiforme/patologia , Qualidade de Vida , Neurofibromatoses/complicações , Neurofibromatoses/terapiaRESUMO
PURPOSE: To present a simplified technique in management of complete ptosis secondary to neurofibromatosis. METHODS: This prospective, non-comparative, clinical interventional study included 13 patients with complete ptosis secondary to histologically proved plexiform neurofibromas. It was conducted at the Orbital Unit of Assiut University Hospital, the referral center of Upper Egypt in the period between June 2013 and October 2021. In all cases, a simplified technique of 5 surgical steps was applied: (A) Division of the involved eyelid surgically into three parts by drawing 2 curvilinear lines, the superior line 11 mm below and parallel to the lower eyebrow hairline and the inferior one 10 mm above the lid margin, (B) Resection (full-thickness) of the large middle part which involves the main pathology and lies between the 2 lines, (C) Preservation of the upper part with identification, dissection and clamping of the levator muscle, (D) Refinement of the lower part by removal of any tissue between the skin and the debulked tarsus and (E) Re-suturing of the upper and lower parts in layers; conjunctiva to conjunctiva, levator to tarsus (after resection of a part that corrects the ptosis) and skin to skin. RESULTS: Ptosis was completely corrected in 8 cases (61.5%) and residual mild ptosis occurred in 5 patients (38.5%). No exposure keratopathy or tumor growth was reported during the follow-up period of minimum 1 year. CONCLUSIONS: This simplified technique could be considered as a surgical basis for correction of complete ptosis in neurofibromatosis.
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Blefaroplastia , Blefaroptose , Neurofibromatoses , Humanos , Blefaroplastia/métodos , Estudos Prospectivos , Blefaroptose/etiologia , Blefaroptose/cirurgia , Pálpebras/cirurgia , Neurofibromatoses/complicações , Neurofibromatoses/cirurgia , Estudos Retrospectivos , Músculos Oculomotores/cirurgiaRESUMO
BACKGROUND: Surgery is a common treatment strategy for patients with neurofibromatosis type 1 (NF1)-related plexiform neurofibroma (PN) and has limited efficacy. FCN-159 is a novel anti-tumorigenic drug via selective inhibition of MEK1/2. This study assesses the safety and efficacy of FCN-159 in patients with NF1-related PN. METHODS: This is a multicenter, open-label, single-arm, phase I dose-escalation study. Patients with NF1-related PN that was non-resectable or unsuitable for surgery were enrolled; they received FCN-159 monotherapy daily in 28-day cycles. RESULTS: Nineteen adults were enrolled in the study, 3 in 4 mg, 4 in 6 mg, 8 in 8 mg, and 4 in 12 mg. Among patients included in dose-limiting toxicity (DLT) analysis, DLTs (grade 3 folliculitis) were reported in 1 of 8 patients (16.7%) receiving 8 mg and 3 of 3 (100%) patients receiving 12 mg. The maximum tolerated dose was determined to be 8 mg. FCN-159-related treatment-emergent adverse events (TEAEs) were observed in 19 patients (100%); most of which were grade 1 or 2. Nine (47.4%) patients reported grade 3 study-drug-related TEAEs across all dose levels, including four experiencing paronychia and five experiencing folliculitis. Of the 16 patients analyzed, all (100%) had reduced tumor size and six (37.5%) achieved partial responses; the largest reduction in tumor size was 84.2%. The pharmacokinetic profile was approximately linear between 4 and 12 mg, and the half-life supported once daily dosing. CONCLUSIONS: FCN-159 was well tolerated up to 8 mg daily with manageable adverse events and showed promising anti-tumorigenic activity in patients with NF1-related PN, warranting further investigation in this indication. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04954001. Registered 08 July 2021.
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Neurofibroma Plexiforme , Neurofibromatose 1 , Humanos , Adulto , Neurofibromatose 1/tratamento farmacológico , Neurofibromatose 1/patologia , Neurofibroma Plexiforme/tratamento farmacológico , Neurofibroma Plexiforme/patologia , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
Neurofibromatosis type 1 is an autosomal dominant multisystemic disease caused by mutation of the neurofibromin (NF1) gene located on chromosome 17q11. We report a case of Neurofibromatosis 1 with ambiguous genitalia, giant congenital melanocytic nevus, and associated subpulmonic outlet ventricular septal defect, hitherto unreported in sub-Saharan Africa. In addition, a literature review of congenital heart diseases associated with Neurofibromatosis 1 is presented.
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Transtornos do Desenvolvimento Sexual , Comunicação Interventricular , Neurofibromatose 1 , Nevo Pigmentado , Humanos , Criança , Neurofibromatose 1/complicações , Neurofibromatose 1/diagnóstico , Neurofibromatose 1/genética , Nevo Pigmentado/diagnóstico , Nevo Pigmentado/genética , Nevo Pigmentado/congênitoRESUMO
INTRODUCTION: Neurofibromatosis type 1 (NF1) is a genetic disorder caused by a mutation in the NF1 gene. This disease presents with various system-based manifestations, including cardiac, musculoskeletal, and neuronal issues, which have been well-studied in previous research and have prompted the development of current and emerging treatments. These treatments, mainly medications targeting specific manifestations of NF1, aim to mitigate the negative impacts of the disease on patients' lives. NF1 is associated with an increased risk of malignancy and a significant decrease in life expectancy. In this paper, we review the current and emerging treatments for NF1 in relation to its system-based manifestations. METHODS: We conducted an extensive literature search using specific keywords through databases such as PubMed, Scopus, and Cochrane. The articles we found were compiled and subjected to strict inclusion and exclusion criteria. RESULTS: Pharmacological advances have led to the development of products that hold promise as future treatments for NF1. Given the diverse manifestations that can affect multiple organ systems in patients with NF1, it is important to consider a variety of treatment options to achieve optimal results. However, one of the major challenges in diagnosing and treating NF1 is that patients present asymptomatically, making it necessary to rely on clinical features for diagnosis. CONCLUSION: In conclusion, NF1 is a complex disease with varying manifestations and a growing field of pharmacologic treatments. The information presented in this article synthesizes current knowledge and available therapies for NF1.
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Neurofibromatose 1 , Humanos , Neurofibromatose 1/complicações , Neurofibromatose 1/genética , Neurofibromatose 1/terapia , Genes da Neurofibromatose 1 , MutaçãoRESUMO
PURPOSE: Neuroendocrine neoplasms can occur as part of inherited disorders, usually in the form of well-differentiated, slow-growing tumors (NET). The main predisposing syndromes include: multiple endocrine neoplasias type 1 (MEN1), associated with a large spectrum of gastroenteropancreatic and thoracic NETs, and type 4 (MEN4), associated with a wide tumour spectrum similar to that of MEN1; von Hippel-Lindau syndrome (VHL), tuberous sclerosis (TSC), and neurofibromatosis 1 (NF-1), associated with pancreatic NETs. In the present review, we propose a reappraisal of the genetic basis and clinical features of gastroenteropancreatic and thoracic NETs in the setting of inherited syndromes with a special focus on molecularly targeted therapies for these lesions. METHODS: Literature search was systematically performed through online databases, including MEDLINE (via PubMed), and Scopus using multiple keywords' combinations up to June 2022. RESULTS: Somatostatin analogues (SSAs) remain the mainstay of systemic treatment for NETs, and radiolabelled SSAs can be used for peptide-receptor radionuclide therapy for somatostatin receptor (SSTR)-positive NETs. Apart of these SSTR-targeted therapies, other targeted agents have been approved for NETs: the mTOR inhibitor everolimus for lung, gastroenteropatic and unknown origin NET, and sunitinib, an antiangiogenic tyrosine kinase inhibitor, for pancreatic NET. Novel targeted therapies with other antiangiogenic agents and immunotherapies have been also under evaluation. CONCLUSIONS: Major advances in the understanding of genetic and epigenetic mechanisms of NET development in the context of inherited endocrine disorders have led to the recognition of molecular targetable alterations, providing a rationale for the implementation of treatments and development of novel targeted therapies.
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Antineoplásicos , Neoplasia Endócrina Múltipla Tipo 1 , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Doença de von Hippel-Lindau , Humanos , Síndrome , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/genética , Antineoplásicos/uso terapêutico , Doença de von Hippel-Lindau/genética , Doença de von Hippel-Lindau/terapia , Everolimo , Neoplasia Endócrina Múltipla Tipo 1/complicações , Somatostatina/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genéticaRESUMO
BACKGROUND: Neurofibromatosis type 1 and pseudoachondroplasia are both rare autosomal dominant disorders, caused by pathogenic mutations in NF1 and COMP genes, respectively. Both neurofibromin 1 and cartilage oligomeric matrix protein (COMP) play a role in the development of the skeleton. Carrying both germline mutations has not been previously reported; however, it can affect the developing phenotype. CASE PRESENTATION: The index patient, an 8-year-old female presented with several skeletal and dermatologic anomalies resembling the coexistence of multiple syndromes. Her mother had dermatologic symptoms characteristic for neurofibromatosis type 1, and her father presented with distinct skeletal anomalies. NGS-based analysis revealed a heterozygous pathogenic mutation in genes NF1 and COMP in the index patient. A previously unreported heterozygous variant was detected for the NF1 gene. The sequencing of the COMP gene revealed a previously reported, pathogenic heterozygous variant that is responsible for the development of the pseudoachondroplasia phenotype. CONCLUSIONS: Here, we present the case of a young female carrying pathogenic NF1 and COMP mutations, diagnosed with two distinct heritable disorders, neurofibromatosis type 1 and pseudoachondroplasia. The coincidence of two monogenic autosomal dominant disorders is rare and can pose a differential diagnostic challenge. To the best of our knowledge, this is the first reported co-occurrence of these syndromes.
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Acondroplasia , Neurofibromatose 1 , Humanos , Feminino , Neurofibromatose 1/complicações , Neurofibromatose 1/diagnóstico , Neurofibromatose 1/genética , Acondroplasia/diagnóstico , Acondroplasia/genética , Mutação , FenótipoRESUMO
Malignant peripheral nerve sheath tumour (MPNST) is an uncommon type of soft tissue tumour which most commonly arises in the setting of Neurofibromatosis-1 (NF-1) or in the presence of another nerve sheath tumour. NF-1 is an autosomal dominant syndrome which is diagnosed based on clinical criteria. People suffering from NF-1 are at a higher risk of developing tumours, especially MPNST. MPNST can occur anywhere along the distribution of nerve roots but most commonly involves the limbs and trunk. The prognosis of MPNST in the setting of NF-1 is grave as the distant metastasis develops earlier than non-syndromic cases. Pre-operative diagnosis is difficult as there is no gold standard radiologic technique or characteristic radiological features. The diagnosis is established after histological evaluation supplemented by immunohistochemistry of the tumour tissue. We present a case of a 38-year-old female, a known case of NF-1, who presented with a single, irregular, cystic swelling in the left flank which was increasing in size. The patient underwent complete surgical excision of a 6cm tumour which was diagnosed as MPNST after histopathological examination. The rare nature of this tumour makes the diagnosis and treatment extremely hard. Awareness regarding this disease should be increased so that proper treatment plans can be made.
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Artrogripose , Cistos Ósseos , Neoplasias Encefálicas , Cistos , Neurofibromatose 1 , Neurofibrossarcoma , Feminino , Humanos , Adulto , Neurofibrossarcoma/diagnóstico por imagem , Neurofibrossarcoma/cirurgia , Neurofibromatose 1/complicações , Neurofibromatose 1/diagnósticoRESUMO
BACKGROUND AND OBJECTIVES: The neurofibromatosis 1 (NF1) diagnosis is challenging in young children without a family history of NF1. The aims of this study were to estimate diagnostic delays in children without a family history of NF1 and to examine the effects of using café au lait macules and skin fold freckling as a single diagnostic criterion. PATIENTS AND METHODS: Retrospective, descriptive, observational study of all patients diagnosed with NF1 before the age of 18 years who were seen at our hospital. The medical records of those included were reviewed to identify the date on which the diagnostic criteria of NF1 were objectified. The patients were categorized into 2 groups: those with a known parental history of NF1 and those without. Café au lait macules and skin fold freckling were assessed as a single diagnostic criterion, and genetic evidence was considered to confirm highly suspicious cases. RESULTS: We studied 108 patients younger than the age of 18 years with a diagnosis of NF1. Mean (SD) age at diagnosis was 3.94 (±3.8) years for the overall group, 1 year for patients with a parental history of NF1, and 4 years and 8 months for those without. Diagnosis was therefore delayed by 3 years and 8 months in patients without a family history. CONCLUSION: Skin lesions were the first clinical manifestation of NF1 in most patients. We believe that the National Institutes of Health's diagnostic criteria for NF1 should be updated to aid diagnosis in young children.
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Melanose , Neurofibromatose 1 , Dermatopatias , Humanos , Criança , Pré-Escolar , Adolescente , Neurofibromatose 1/diagnóstico , Neurofibromatose 1/genética , Neurofibromatose 1/patologia , Estudos Retrospectivos , Manchas Café com Leite/diagnósticoRESUMO
Cognitive dysfunction is among the hallmark symptoms of Neurofibromatosis 1, and accordingly, loss of the Drosophila melanogaster ortholog of Neurofibromin 1 (dNf1) precipitates associative learning deficits. However, the affected circuitry in the adult CNS remained unclear and the compromised mechanisms debatable. Although the main evolutionarily conserved function attributed to Nf1 is to inactivate Ras, decreased cAMP signaling on its loss has been thought to underlie impaired learning. Using mixed sex populations, we determine that dNf1 loss results in excess GABAergic signaling to the central for associative learning mushroom body (MB) neurons, apparently suppressing learning. dNf1 is necessary and sufficient for learning within these non-MB neurons, as a dAlk and Ras1-dependent, but PKA-independent modulator of GABAergic neurotransmission. Surprisingly, we also uncovered and discuss a postsynaptic Ras1-dependent, but dNf1-independnet signaling within the MBs that apparently responds to presynaptic GABA levels and contributes to the learning deficit of the mutants.
Assuntos
Aprendizagem por Associação/fisiologia , Proteínas de Drosophila/metabolismo , Corpos Pedunculados/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Ácido gama-Aminobutírico/metabolismo , Proteínas Ativadoras de ras GTPase/metabolismo , Animais , AMP Cíclico/metabolismo , Drosophila melanogaster , Transdução de Sinais/fisiologia , Proteínas ras/metabolismoRESUMO
Neurofibromatosis 1 (NF1) is caused by germline mutations in the NF1 gene and manifests as proliferation of various tissues, including plexiform neurofibromas. The plexiform neurofibroma phenotype varies from indolent to locally aggressive, suggesting contributions of other modifiers in addition to somatic loss of NF1. In this study, we investigated a life-threatening plexiform neurofibroma in a 9-month-old female infant with NF1. Germline mutations in two RASopathy-associated genes were identified using whole-exome sequencing-a de novo pathogenic variant in the NF1 gene, and a known pathogenic variant in the LZTR1 gene. Somatic analysis of the plexiform neurofibroma revealed NF1 loss of heterozygosity and a variant in GNAZ, a gene encoding a G protein-coupled receptor. Cells expressing mutant GNAZ exhibited increased ERK 1/2 activation compared to those expressing wild-type GNAZ. Taken together, we suggest the variants in NF1, LZRT1 and GNAZ act synergistically in our patient, leading to MAPK pathway activation and contributing to the severity of the patient's plexiform neurofibromatosis. After treatment with the MEK inhibitor, trametinib, a prominent clinical improvement was observed in this patient. This case study contributes to the knowledge of germline and somatic non-NF1 variants affecting the NF1 clinical phenotype and supports use of personalized, targeted therapy.
Assuntos
Neurofibroma Plexiforme , Neurofibromatose 1 , Feminino , Subunidades alfa de Proteínas de Ligação ao GTP/genética , Subunidades alfa de Proteínas de Ligação ao GTP/metabolismo , Heterozigoto , Humanos , Quinases de Proteína Quinase Ativadas por Mitógeno , Neurofibroma Plexiforme/tratamento farmacológico , Neurofibroma Plexiforme/genética , Neurofibroma Plexiforme/metabolismo , Neurofibromatose 1/tratamento farmacológico , Neurofibromatose 1/genética , Neurofibromatose 1/patologia , Neurofibromina 1 , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Fatores de Transcrição/genéticaRESUMO
Neurofibromatosis type 1 (NF1) is a common neurocutaneous disorder characterized by development of pigmentary skin changes, neurogenic tumors, and other manifestations involving multiple organ systems. Penetrance is complete, though expressivity is quite variable even among the family members. Given that NF1 is a common hereditary condition, existence of a second genetic disorder in NF1 patients is not unexpected. During comprehensive evaluations of individuals with NF1, we encountered 11 patients with dual diagnosis who contributed to phenotypic complexity and challenges for long-term management. Examples include Prader-Willi Syndrome, Autosomal Dominant Polycystic Kidney Disease, Down syndrome, infantile myofibromatosis, Craniosynostosis, cleft lip and palate, 47,XYY, 22q11.2 duplication, 15q13.3 deletion syndrome, and BRCA2- and ATM- related cancer predisposition syndromes. Presence of dysmorphism, developmental delay, atypical tumors, and family history of other genetic disorders including cancers appears as determinants to consider a second genetic etiology and helps to differentiate from an extreme phenotypic spectrum of NF1. Clinicians should have high index of suspicion to exclude coexisting disorders, as apart from providing comprehensive medical care. This also has potential implications in genetic counseling. Long-term effects of the synergistic mechanisms leading to phenotypic complexity and patient outcomes are yet to be characterized, with follow-up needed.
Assuntos
Fenda Labial , Fissura Palatina , Deficiência Intelectual , Neurofibromatose 1 , Deleção Cromossômica , Fenda Labial/genética , Fissura Palatina/genética , Humanos , Deficiência Intelectual/genética , Neurofibromatose 1/diagnóstico , Neurofibromatose 1/genética , Neurofibromatose 1/terapiaRESUMO
PURPOSE OF REVIEW: Tuberous sclerosis complex (TSC) and neurofibromatosis (NF) are neurocutaneous disorders often encountered by neurologists in clinical practice. This article aims to familiarize adult and pediatric neurologists with common features of these disorders and headache specific evaluation and management. RECENT FINDINGS: Non-malignant intracranial tumors in TSC include cortical tubers (glioneuronal hamartomas), subependymal nodules or subependymal giant-cell astrocytomas (SEGA). Headache disorders in TSC are largely secondary and can cause headaches due to increased intracranial pressure, mass effect, obstructive hydrocephalus, or hemorrhage. Neurosurgical intervention is typically required for management of large SEGAs; however, in patients with increased surgical risk, newer treatment modalities may be offered such as neoadjuvant therapy with an mTOR inhibitor (mTORi). Newer studies indicate headache disorders are more prevalent in neurofibromatosis type 1 (NF1). Primary headache disorders can include migraine and tension-type headache, while secondary headache disorders can be due to associated neoplasms such as optic pathway gliomas or brainstem gliomas, or less commonly vasculopathies such as moyamoya syndrome. Selumetinib is an oral, small molecule mitogen-activated protein kinase (MEK) agent with antineoplastic activity which is in ongoing trials for treatment of NF1-associated pediatric low-grade gliomas. NF1 stands out as having a higher association with primary headache disorders such as migraine. This association may be related to effects of mutation of the neurofibromin gene on pathways involved in pain and migraine genesis, however, warrants future study. Care should be taken when formulating a headache treatment plan to address comorbidities and avoid medications that may be contraindicated.
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Astrocitoma , Neoplasias Encefálicas , Transtornos da Cefaleia Primários , Transtornos da Cefaleia , Transtornos de Enxaqueca , Neurofibromatose 1 , Esclerose Tuberosa , Adulto , Astrocitoma/genética , Astrocitoma/metabolismo , Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Criança , Cefaleia/complicações , Cefaleia/terapia , Transtornos da Cefaleia/complicações , Transtornos da Cefaleia Primários/complicações , Humanos , Transtornos de Enxaqueca/complicações , Neurofibromatose 1/complicações , Neurofibromatose 1/genética , Neurofibromatose 1/terapia , Esclerose Tuberosa/complicações , Esclerose Tuberosa/genética , Esclerose Tuberosa/terapiaRESUMO
Optic pathway gliomas are the most common central nervous system neoplasms in patients with neurofibromatosis type 1. Perineural arachnoidal gliomatosis is a rare and distinctive growth pattern of optic nerve glioma, in which the tumor infiltrates through the pia mater and pre-dominantly involves the subarachnoid space around the optic nerve. Here, we report an 8-year-old girl with perineural arachnoidal gliomatosis associated with neurofibromatosis type 1.
Assuntos
Neurofibromatose 1 , Glioma do Nervo Óptico , Aracnoide-Máter/patologia , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Neurofibromatose 1/complicações , Neurofibromatose 1/diagnóstico por imagem , Neurofibromatose 1/patologia , Nervo Óptico/patologia , Glioma do Nervo Óptico/complicaçõesRESUMO
BACKGROUND/OBJECTIVES: Café-au-lait macules (CALMs) are a characteristic feature of neurofibromatosis type 1 (NF1), but also occur in other genetic disorders. Differential diagnosis of CALMs remains challenging and can be stressful for families. We sought to examine the role of an established CALMs screening clinic in diagnosing CALMs-related disorders. METHOD: We retrospectively reviewed patients seen between July 2012 and January 2019 in a CALMs screening clinic at The Hospital for Sick Children, a tertiary pediatric hospital in Toronto, Canada. Pediatric patients were referred because of multiple CALMs or suspected NF1. Selection was based on a chronological referral sample with no exclusions. A pediatric dermatologist examined all patients for CALMs and NF1 manifestations. Genetic testing was offered to confirm a clinical diagnosis or when clinical findings were inconclusive. RESULTS: Three hundred patients, of which 152 (50.7%) were female and had a mean age of 5.6 ± 4.8 years were seen during the study period. NF1 was diagnosed in 76 (25.3%) patients, mosaic NF1 in 38 (12.7%) patients, and 8 (2.7%) patients received other genetic diagnoses. One hundred and twelve (37.3%) patients were diagnosed with isolated CALMs not associated with an underlying genetic disease. Furthermore, 36 (12%) of our patients did not have CALMs. CONCLUSIONS: The CALMs screening clinic aided in the early diagnosis of genetic disorders such as NF1 and distinguished CALMs from other hyperpigmented lesions. We encourage the adoption of this clinic model in referral centers to streamline and optimize care of patients with presumptive diagnosis of CALMs.
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Manchas Café com Leite , Neurofibromatose 1 , Manchas Café com Leite/complicações , Criança , Pré-Escolar , Feminino , Testes Genéticos , Hospitais , Humanos , Lactente , Masculino , Neurofibromatose 1/complicações , Neurofibromatose 1/diagnóstico , Neurofibromatose 1/genética , Estudos RetrospectivosRESUMO
OBJECTIVES: The aim of this study was to evaluate the mandibular condyles of neurofibromatosis 1 (NF1) individuals without facial plexiform neurofibroma using cone beam computed tomography images. MATERIALS AND METHODS: Eighty cone beam computed tomography scans (160 mandibular condyles) were analyzed: 40 from NF1 individuals (study group) and 40 from individuals without NF1 (control group). The anteroposterior and mediolateral dimensions, height, and volume of the mandibular condyles were measured. The mandibular condyles were classified according to their morphology: healthy (absence of morphological changes), with flattening (loss of rounded contour of at least one of the surfaces), with erosion (loss of continuity of the cortical bone), with osteophyte (exophytic formation of the condyle surface), and with sclerosis (any increase in the cortical thickness in the load-bearing areas). Furthermore, the position of the mandibular condyles in relation to the joint fossa in an anteroposterior view was classified as anterior, concentric, or posterior. RESULTS: The study group had a higher anteroposterior dimension of the mandibular condyles compared with the control group (p < 0.05). There were no differences in condylar morphology and position between both groups (p > 0.05). The morphological alterations were not associated with sex or age in any group evaluated (p > 0.05). For both groups, the concentric position was the most common. For the study group, there was a significant difference in the condylar position between the sides (p < 0.05). CONCLUSIONS: NF1 individuals without facial plexiform neurofibroma present a high prevalence of condyles with a large anteroposterior dimension and asymmetric position in the joint fossa. However, no morphological and volumetric changes were observed in the mandibular condyles of them. CLINICAL RELEVANCE: The knowledge of the TMJ alterations in individuals with NF1 is important to establish an evaluation protocol, which would allow early intervention if indicated.
Assuntos
Côndilo Mandibular , Neurofibromatose 1 , Estudos de Casos e Controles , Tomografia Computadorizada de Feixe Cônico , Humanos , Côndilo Mandibular/diagnóstico por imagem , Neurofibromatose 1/diagnóstico por imagem , Articulação TemporomandibularRESUMO
Vertebro-vertebral fistula involving the V3 segment of the vertebral artery is a rare vascular pathology which is either spontaneous or traumatic in origin. We describe a post-operative traumatic vertebro-vertebral fistula in a 47-year old lady with NF-1. We review reported cases of V3 segment vertebrovertebral fistula for their incidence, aetiology, clinical presentation, treatment and outcomes using an illustrative case. Traumatic V3 segment vertebrovertebral fistula is predominantly managed with parent vessel occlusion. Per the algorithm presented, we suggest endovascular management of non-traumatic fistula be based on the anatomical variance of the contralateral vertebral artery.
RESUMO
BACKGROUND: The diagnosis of Neurofibromatosis type 1 (NF1) is usually delayed in children without a family history. We aimed to define the prevalence and characteristics of prevalent skin manifestations in NF1 compared to the general population, which continue to be excluded from the diagnostic criteria for NF1. PATIENTS AND METHODS: Case-control study, matched by age groups, in which 108 patients with a diagnosis of NF1 and 137 healthy controls were included. RESULTS: The prevalence of nevus anemicus (NA) (P<.001) and juvenile xanthogranulomas (JXG) (P<.001) was significantly higher in the population affected by NF1 than in the control population. A specificity of 99.27% (confidence interval): 95.4-99.96%] and a positive predictive value (PPV) of 98.80% [92.54-99.94%] were estimated for NA and a specificity of 99.27% [95.4-99.96%] and a PPV of 92.86% [64.17-99.63%] for JXG in the diagnosis of NF1 in children who present 6 or more Café-au-lait macules. Statistically significant differences were also evidenced in the distribution by phototypes (P=.025) and in relation to generalized itching with no other cause (P<.001). CONCLUSIONS: NA and JXG are relevant clinical findings for the diagnosis of NF1, especially during the first years of life. We consider that its inclusion among the diagnostic criteria of the disease should be evaluated.
Assuntos
Neurofibromatose 1 , Transtornos da Pigmentação , Xantogranuloma Juvenil , Criança , Humanos , Neurofibromatose 1/diagnóstico , Neurofibromatose 1/epidemiologia , Estudos de Casos e Controles , Manchas Café com Leite/diagnóstico , Prevalência , InflamaçãoRESUMO
BACKGROUND: The diagnosis of Neurofibromatosis type 1 (NF1) is usually delayed in children without a family history. We aimed to define the prevalence and characteristics of prevalent skin manifestations in NF1 compared to the general population, which continue to be excluded from the diagnostic criteria for NF1. PATIENTS AND METHODS: Case-control study, matched by age groups, in which 108 patients with a diagnosis of NF1 and 137 healthy controls were included. RESULTS: The prevalence of nevus anemicus (NA) (p<0.001) and juvenile xanthogranulomas (JXG) (p<0.001) was significantly higher in the population affected by NF1 than in the control population. A specificity of 99.27% [confidence interval (CI): 95.4-99.96%] and a positive predictive value (PPV) of 98.80% [92.54-99.94%] were estimated for NA and a specificity of 99.27% [95.4-99.96%] and a PPV of 92.86% [64.17-99.63%] for JXG in the diagnosis of NF1 in children who present 6 or more Café-au-lait macules. Statistically significant differences were also evidenced in the distribution by phototypes (p 0.025) and in relation to generalized itching with no other cause (p<0.001). CONCLUSIONS: NA and JXG are relevant clinical findings for the diagnosis of NF1, especially during the first years of life. We consider that its inclusion among the diagnostic criteria of the disease should be evaluated.