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At least 1,621 records · Page 90Linked to original sources
PubMed2006

Quality of life and psychological adjustment in children and adolescents with neurofibromatosis type 1.

OBJECTIVE: To assess quality of life (QoL) and psychological adjustment in children and adolescents with neurofibromatosis type 1 (NF1). STUDY DESIGN: Forty-six patients with NF1 were investigated between the ages of 7 and 16 years (mean, 11.6 years), with children and parents used as informants. TNO-AZL Questionnaire for Children's Health-Related Quality of Life and Child Behavior Checklist scores were compared with healthy reference groups. Predictive values of sociodemographic variables, illness-related variables, and family-related variables for quality of life and psychological adjustment were assessed. RESULTS: Most dimensions of QoL in NF1 children and adolescents were different from reference values. Deviations in the NF1 group were an impairment of motor, cognitive, and social functioning and a reduction of positive and negative emotions. Also, psychological adjustment in patients with NF1 was significantly impaired compared with normal subjects. Illness-related variables had a negative impact on the emotional domain of QoL. Good family relationships positively affected both QoL and psychological adjustment. CONCLUSIONS: QoL and psychological adjustment are impaired in children and adolescents with NF1. Illness-related variables and the quality of family relationships are important predictors.

Adaptation, Psychological↗
PubMed2006

Sudden cardiac death in young children with neurofibromatosis type 1.

Patients with neurofibromatosis type 1 (NF1) can manifest a characteristic vasculopathy that in adults is rarely associated with fatal coronary artery occlusion. We describe the clinical and pathological findings from 2 unrelated young children with NF1, a similar vasculopathy affecting their coronary arteries, and sudden cardiac death.

Child↗
PubMed2007

Bone mineral density in children and adolescents with neurofibromatosis type 1.

OBJECTIVE: To assess whether children and adolescents with neurofibromatosis type 1 (NF1) have decreased bone mineral density (BMD). STUDY DESIGN: Bone densitometry of the whole body, hip, and lumbar spine was used in a case-to-control design (84 individuals with NF1: 293 healthy individuals without NF1). Subjects were 5 to 18 years old. Subjects with NF1 were compared with control subjects by using an analysis-of-covariance with a fixed set of covariates (age, weight, height, Tanner stage, and sex). RESULTS: Subjects with NF1 had decreased areal BMD (aBMD) of the hip (P <.0001), femoral neck (P <.0001), lumbar spine (P = .0025), and whole body subtotal (P <.0001). When subjects with NF1 were separated in groups with and without a skeletal abnormality, those who did not have a skeletal abnormality still had statistically significant decreases in aBMD compared with control subjects (P <.0001 for whole body subtotal aBMD), although they were less pronounced than in those with osseous abnormalities. CONCLUSIONS: These data suggest that individuals with NF1 have a unique generalized skeletal dysplasia, predisposing them to localized osseous defects. Dual energy x-ray absorptiometry may prove useful in identifying individuals with NF1 who are at risk for clinical osseous complications and monitoring therapeutic trials.

Absorptiometry, Photon↗
PubMed2004

Human blood genomics: distinct profiles for gender, age and neurofibromatosis type 1.

Application of gene expression profiling to human diseases will be limited by availability of tissue samples. It was postulated that germline genetic defects affect blood cells to produce unique expression patterns. This hypothesis was addressed by using a test neurological disease-neurofibromatosis type 1 (NF1), an autosomal dominant genetic disease caused by mutations of the NF1 gene at chromosome 17q11.2. Oligonucleotide arrays were used to survey the blood gene expression pattern of 12 NF1 patients compared to 96 controls. A group of genes related to tissue remodeling, bone development and tumor suppression were down-regulated in NF1 blood samples. In addition, there were blood genomic patterns for gender and age: Y chromosome genes showing higher expression in males, indicating a gene-dosage effect; and genes related to lymphocyte functions showing higher expression in children. The results suggest that genetic mutations can be manifested at the transcriptional level in peripheral blood cells and blood gene expression profiling may be useful for studying phenotypic differences of human genetic diseases and possibly providing diagnostic and prognostic markers.

Adolescent↗
PubMed2004

Genetic and phenotypic characterization of tumor cells derived from malignant peripheral nerve sheath tumors of neurofibromatosis type 1 patients.

Neurofibromatosis type 1 (NF1) patients have an 8-13% lifetime risk of developing malignant peripheral nerve sheath tumors (MPNST) which have a very poor prognosis. In this study, cells from eight MPNSTs (six primary and two recurrences) of six clinically and genetically well-characterized NF1 patients were taken into culture. Tracing of loss of heterozygosity (LOH) of the NF1, p53, and p16 gene regions or of abnormal karyotypes enabled identification of tumor cells from five MPNSTs. In two other MPNST-derived cell cultures, LOH of the relevant regions in the original tumors could not be detected, indicating that the obtained cells were nonneoplastic cells. Cells from most MPNSTs grew only under standard culture conditions but not under conditions optimized for Schwann cells. These cells were S100-negative and did not exhibit spindle shape which is a characteristic of Schwann cells. Drastically increased proliferation rates were found for most of the MPNST cells in comparison to Schwann cells derived from benign neurofibromas. Our study demonstrates that genetic analysis is effective and essential for verification of MPNST tumor cells in culture. These verified MPNST cells are valuable for further investigations of the biology and pathogenesis of this malignancy as well as for in vitro pharmacologic studies essential for the development of new therapies.

Adult↗
PubMed2004

Functional MRI of visual-spatial processing in neurofibromatosis, type I.

Visual-spatial impairment and neuroanatomical abnormalities are considered hallmark features of neurofibromatosis, type I (NF-I). Numerous studies have demonstrated visual-spatial deficits in children with NF-I, but few relations between these deficits and neuroanatomical abnormalities have been identified. We compared the functional neuroanatomy of cerebral regions involved in the spatial transformation of alphanumeric stimuli in individuals with NF-I and healthy control participants using functional magnetic resonance imaging (fMRI). Given the prevalence of visual pathway abnormalities and visual-spatial deficits in NF-I, we hypothesized that less neuronal hemodynamic activity would be found in occipital and parietal cortices in this group compared with controls. However, NF-I participants relied to a greater degree than controls on posterior cortex (including occipital, parietal, and middle temporal cortices) relative to lateral and inferior frontal regions during visual-spatial analysis. This pattern was significantly related to their behavioral performance on the fMRI task, which in turn was also positively correlated with reading scores. These findings support evidence of frontal cortical anomalies in NF-I and may provide a pathophysiological basis for cognitive deficits in NF-I.

Adolescent↗
PubMed2004

Orbitotemporal neurofibromatosis. Clinical features and surgical management.

PURPOSE: To classify the periorbital deformities of adult orbitotemporal neurofibromatosis (NF) and describe new clinical findings, and to recommend guidelines for surgical treatment and management of surgical complications. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Thirty-three patients over age 16 with orbitotemporal NF. METHODS: Retrospective surgical case record and serial photographic review recording the laterality and the severity of periorbital involvement, the presence of complications from previous surgery, the surgical techniques undertaken, and the surgical outcome and complications. MAIN OUTCOME MEASURES: Comparison of preoperative and postoperative level of deformities. RESULTS: New classification of periorbital deformities: (1) brow ptosis, (2) upper lid infiltration with ptosis, (3) lower lid infiltration, (4) lateral canthal disinsertion, and (5) conjunctival and lacrimal gland infiltration. Two patients had bilateral and 31 patients (94%) had unilateral orbitotemporal NF. All patients had upper and 19 patients (58%) had lower lid involvement. Six (18%) patients had significant brow infiltration. Fourteen (42%) patients had a dropped lateral canthus requiring surgical reattachment, 28 (85%) required anterior levator resection for ptosis, and 28 (85%) had lid-debulking surgery. New findings included severe brow infiltration, lacrimal gland involvement, and functional nasolacrimal duct obstruction. Complications from previous surgery included residual ptosis, ptosis overcorrection, poor lid contour, dry eye, corneal exposure, and upper and lower lid entropion/ectropion. CONCLUSIONS: The periorbital appearance and comfort of patients with NF type 1 who have orbitotemporal NF can be significantly improved through oculoplastic surgery.

Adolescent↗
PubMed2005

Current concepts in the evaluation and treatment of neurofibromatosis type II.

This article presents the current diagnostic and treatment options for the hereditary disease neurofibromatosis type II, reviews clinical presentation and diagnosis, highlights indications for and methods of clinical and genetic screening, discusses treatment approaches for surgery and stereotactic radiation, and summarizes potential future therapeutic avenues.

Decompression, Surgical↗
PubMed2006

Clinical manifestations and management of neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with variable expression. The complications are age specific. Neurologic complications include tumors of the peripheral nerves, nerve roots, and plexi; spinal cord compression; dural ectasias; learning disabilities; attention deficit; headaches; seizures; brain tumors; deafness; hydrocephalus; and stroke. High-intensity signals on brain magnetic resonance imaging are a frequent finding without known clinical significance. Most brain tumors are benign and asymptomatic, but malignant brain tumors occur. The major cause of death is malignancy, including brain tumors and malignant peripheral nerve sheath tumors. Management includes genetic counseling, regular eye examinations, and careful physical exams.

Age Factors↗
PubMed2006

Cognitive profile of neurofibromatosis type 1.

General consensus has yet to be reached with regard to the exact cognitive profile of children with neurofibromatosis type 1 (NF1). The current overview seeks to provide a more comprehensive review of the literature by examining studies that have specifically compared individuals with NF1 to siblings, controls, and/or norms. We also examined results of studies that compared individuals with NF1 with various manifestations to each other. Consistent with previous reviews, no clear cognitive profile emerged; however, greater insight into patterns was obtained. Additionally, future directions for research on NF1 were suggested.

Cognition↗
PubMed2006

Assessment of sacrum scalloping in neurofibromatosis type 1 caused by a giant cell lesion of the sacrum.

BACKGROUND: Neurofibromatosis type 1 (NF-1) is the most common of the neurocutaneous disorders. It leads to significant orthopedic complications and spinal deformities. Scalloping in NF-1 may be caused by weakness of the mesodermal dysplasia, which develops through the inherited mutation of chromosome 17. Aneurysmal bone cysts (ABCs) are rare, rapidly expanding, locally destructive, and often misdiagnosed lesions. Assessment of sacrum scalloping in NF-1 caused by aneurysmal bone cyst is described. CASE DESCRIPTION: A 15-year-old male was a patient with NF-1. He presented with cramping pain of the left soleus muscle, which had developed over the previous 3 months. The magnetic resonance imaging of the lumbar-sacrum region revealed a well-circumscribed multiloculated lesion located in the dorsal sacrum region and causing posterior vertebral scalloping and compression of nerve roots. The preoperative clinical suspicion was of a neurofibroma, a giant cell granuloma, or a lymphoma. However, the histopathologic diagnosis was consistent with ABC of the sacrum. This differed from our preoperative suspicion. CONCLUSION: The etiology of ABCs is still unknown. Some researchers have described ABCs with chromosomal abnormalities of 16q22 and/or 17p13. This is consistent with NF-1, which develops through the inherited mutation of chromosome 17. Therefore, mutation of the chromosome may play an important role in the development of NF-1 and ABCs. Adequate diagnosis is necessary before treatment or biopsy of ABCs because bleeding may occur during operation or biopsy. Surgery is the treatment of choice for most ABCs. Adjuvant megavoltage radiotherapy is indicated for patients with recurrent tumors and whose tumors are inoperable.

Adolescent↗
PubMed2006

Spontaneous spinal epidural arteriovenous fistulae in neurofibromatosis type-1.

BACKGROUND: NF-1 is one of the most common autosomal-dominantly inherited genetic disorders with an incidence of approximately 1:3500. We report a case and review the literature to characterize spontaneous spinal AVF that occur in neurofibromatosis (NF-1). CASE REPORT: A 51-year-old woman presented with NF-1 and progressive radiculomyelopathy. Angiography revealed an AVF terminating in a giant intraspinal epidural varix extending paraspinally through the C3/4 neural foramen. Trapping of the AVF attempted 18 years earlier prevented endovascular access for embolization, and vigorous bleeding made direct surgical resection impossible. Therefore, as palliation, arterial feeding collaterals were occluded, and surgically exposed tortuous veins were packed with coils. Laminectomies and partial resection of the epidural varix resulted in subtotal occlusion with clinical improvement. CONCLUSION: The spinal AVF associated with NF-1 appears to show dominant venous drainage to the intraspinal extradural and paraspinal venous plexus without evidence of intradural drainage. The vertebral artery is typically the origin of the fistula. A giant venous varix and numerous collateral feeders to the vertebral artery may give an AVM-like appearance. Clinically, the fistulae produce a syndromic triad including symptoms of NF-1, progressive radiculomyelopathy, and a bruit. Treatment is direct attack on the fistula by either surgery or embolization. If, however, a direct approach cannot be chosen, occlusion of feeding vessels combined with laminectomies can result in long-term symptomatic improvement.

Arteriovenous Fistula↗
PubMed2006

Clinically aggressive central giant cell granulomas in two patients with neurofibromatosis 1.

BACKGROUND: Neurofibromatosis 1 (NF1) is an autosomal dominantly inherited disorder caused by a spectrum of mutations affecting the Nf1 gene. Affected patients develop benign and malignant tumors at an increased frequency. Clinical findings include multiple cutaneous café-au-lait pigmentations, neurofibromas, axillary freckling, optic gliomas, benign iris hamartomas (Lisch nodules), scoliosis, and poorly defined soft tissue lesions of the skeleton. Kerl first reported an association of NF1 with multiple central giant cell granulomas (CGCGs) of the jaws. There have since been 4 additional published cases of NF1 patients with CGCGs of the jaws. CLINICAL CASES: We report on 2 patients who presented with NF1 and aggressive CGCGs of the jaws. In both cases, the clinical course was characterized by numerous recurrences despite mechanical curettage and surgical resection. CONCLUSIONS: We review proposed mechanisms to explain the apparent association between NF1 and an increased incidence of CGCGs of the jaws. While the presence of CGCGs of the jaws in patients with NF1 could represent either a coincidental association or a true genetic linkage, we propose that this phenomenon is most likely related to NF1-mediated osseous dysplasia. Compared to normal bone, the Nf1-haploinsufficient bone in a patient with NF1 may be less able to remodel in response to as of yet unidentified stimuli (e.g. excessive mechanical stress and/or vascular fragility), and consequently may be more susceptible to developing CGCG-like lesions. Alternatively, the CGCG in NF1 patients could represent a true neoplasm, resulting from additional, as of yet unidentified, genetic alterations to Nf1-haploinsufficient bone.

Adult↗
PubMed1976

Idiopathic hypertrophic subaortic stenosis associated with cutaneous neurofibromatosis: report of a case.

Although idiopathic hypertrophic subaortic stenosis has been studied extensively, its etiology has remained elusive. Recent reports of its association with neuroectodermal syndrome suggest that at least some cases may be the manifestation of a heritable defect of neuroectoderm. Consistent with this hypothesis, we report a case of idiopathic hypertrophic subaortic stenosis associated with neurofibromatosis.

Aortic Stenosis, Subvalvular↗
PubMed1998

Neurofibromatosis type 1 with pregnancy-associated renovascular hypertension and the syndrome of hemolysis, elevated liver enzymes, and low platelets.

The authors detected a case of neurofibromatosis type 1 complicated with preeclampsia and the syndrome of hemolysis, elevated liver enzymes, and low platelets, which developed during pregnancy. When the cause of the patient's hypertension was investigated after birth, renal stenosis of the right artery was detected, which was then successfully treated with percutaneous transluminal angioplasty.

Adult↗
PubMed1991

Magnetic resonance imaging signs of optic nerve gliomas in neurofibromatosis 1.

We reviewed the magnetic resonance images of four children with neurofibromatosis 1 and orbital optic gliomas. The images showed double-intensity tubular thickening characteristic of perineural arachnoidal gliomatosis, elongation of the nerves, and downward kinking of the nerves in the midorbit. We believe these findings typify the orbital gliomas in patients with this disease.

Adolescent↗
PubMed2001

The neurofibromatosis type 2 gene is mutated in perineurial cell tumors: a molecular genetic study of eight cases.

Perineurial cell tumors (PNTs) are rare neoplasms derived from or showing differentiation toward specialized lining cells of the nerve sheath, the perineurial cells. In this study, we have evaluated neurofibromatosis type 2 (NF2) gene alterations in eight PNTs using archival formaldehyde-fixed, paraffin-embedded tissue. Two conventional soft-tissue PNTs from the upper back and chest wall, one retiform soft tissue variant from the scapular region, and five sclerosing PNTs from the fingers and palm were studied. All cases showed histological features of PNTs, and the neoplastic cells were positive for epithelial membrane antigen and negative for S100 protein. The coding sequences (exons 1 to 15) of the NF2 gene were polymerase chain reaction (PCR) amplified and evaluated for mutations by direct sequencing of the PCR products. Five NF2 point mutations, two in the 5'-untranslated region (UTR) and three in exons 3, 6, and 8, were identified in four of eight cases (50%) studied. Exon mutations resulted in changes of predicted amino acids sequences: Asp-->Asn at codon 83, Glu-->Asp at codon 182, and Leu-->Val at codon 241. In two cases (one with a missense mutation in codon 241), the same point mutation in the 5'-UTR at the nucleotide position 8958 was identified. A loss of heterozygosity (LOH) study was performed in three cases. LOH at the NF2 locus was found in one case with a mutation in the 5'-UTR. However, in another case with exon 8 and 5'-UTR mutations, deletion of one allele of the NF2 gene was previously documented by fluorescence in situ hybridization. The coexistence of NF2 gene mutations and LOH at the NF2 locus indicates that the NF2 tumor suppressor gene is altered in PNTs by the two-hit mechanism.

Adolescent↗
PubMed1999

Malignant transformation of neurofibromas in neurofibromatosis 1 is associated with CDKN2A/p16 inactivation.

Patients with neurofibromatosis 1 (NF1) are predisposed to develop multiple neurofibromas (NFs) and are at risk for transformation of NFs to malignant peripheral nerve sheath tumors (MPNSTs). Little is known, however, about the biological events involved in the malignant transformation of NFs. We examined the CDKN2A/p16 gene and p16 protein in NFs and MPNSTs from patients with NF1. On immunohistochemical analysis, all NFs expressed p16 protein. The MPNSTs, however, were essentially immunonegative for p16, with striking transitions in cases that contained both benign and malignant elements. None of the benign tumors had CDKN2A/p16 deletions, whereas three of six MPNSTs appeared to have homozygous CDKN2A/p16 deletions. Methylation analysis and mutation analysis of CDKN2A/p16 in MPNSTs did not reveal any abnormalities. These results show that malignant transformation of NF is associated with loss of p16 expression, which is often secondary to homozygous deletion of the CDKN2A/p16 gene. The findings suggest that CDKN2A/p16 inactivation occurs during the malignant transformation of NFs in NF1 patients and raises the possibility that p16 immunohistochemistry may provide ancillary information in the distinction of NF from MPNST.

Adolescent↗