scholarly journals Natural history of NF1 c.2970_2972del p.(Met992del): confirmation of a low risk of complications in a longitudinal study

2021 ◽  
Author(s):  
Claire Forde ◽  
Emma Burkitt-Wright ◽  
Peter D. Turnpenny ◽  
Eric Haan ◽  
John Ealing ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Significant Proportion ◽  
Learning Difficulties ◽  
Clinical Information ◽  
Neurofibromatosis Type ◽  
Base Pair Deletion ◽  
History Of ◽  
Subcutaneous Lesion ◽  
Over Time

AbstractIndividuals with the three base pair deletion NM_000267.3(NF1):c.2970_2972del p.(Met992del) have been recognised to present with a milder neurofibromatosis type 1 (NF1) phenotype characterised by café-au-lait macules (CALs) and intertriginous freckling, as well as a lack of cutaneous, subcutaneous and plexiform neurofibromas and other NF1-associated complications. Examining large cohorts of patients over time with this specific genotype is important to confirm the presentation and associated risks of this variant across the lifespan. Forty-one individuals with the in-frame NF1 deletion p.Met992del were identified from 31 families. Clinicians completed a standardised clinical questionnaire for each patient and the resulting data were collated and compared to published cohorts. Thirteen patients have been previously reported, and updated clinical information has been obtained for these individuals. Both CALs and intertriginous freckling were present in the majority of individuals (26/41, 63%) and the only confirmed features in 11 (27%). 34/41 (83%) of the cohort met NIH diagnostic criteria. There was a notable absence of all NF1-associated tumour types (neurofibroma and glioma). Neurofibroma were observed in only one individual—a subcutaneous lesion (confirmed histologically). Nineteen individuals were described as having a learning disability (46%). This study confirms that individuals with p.Met992del display a mild tumoural phenotype compared to those with ‘classical’, clinically diagnosed NF1, and this appears to be the case longitudinally through time as well as at presentation. Learning difficulties, however, appear to affect a significant proportion of NF1 subjects with this phenotype. Knowledge of this genotype–phenotype association is fundamental to accurate prognostication for families and caregivers.

scholarly journals Clinical and Cytometric Study of Immune Involvement in a Heterogeneous Cohort of Subjects With RASopathies and mTORopathies

2021 ◽  
Vol 9 ◽  
Author(s):  
Erica Valencic ◽  
Prisca Da Lozzo ◽  
Gianluca Tornese ◽  
Elena Ghirigato ◽  
Francesco Facca ◽  
...  
Keyword(s):  
Significant Proportion ◽  
Neurofibromatosis Type ◽  
Genetic Syndromes ◽  
Intravenous Antibiotic ◽  
Immature B Cells ◽  
Invasive Infections ◽  
History Of ◽  
Altered Cell ◽  
Immune Disturbance

RASopathies and mTORopathies are groups of genetic syndromes associated with increased activation of the RAS-MAPK or the PI3K-AKT-mTOR pathway, resulting in altered cell proliferation during embryonic and postnatal development. The RAS-MAPK and the PI3K-AKT-mTOR pathways are connected to each other and play a crucial role in adaptive immunity. However, with the exception of Activated PI3K delta syndrome (APDS), immune function has not been deeply studied in these disorders. We collected clinical and immunophenotypic data of a cohort of patients with RASopathies and mTORopathies. Overall, we enrolled 47 patients (22 females, 25 males, age 2–40 years): 33 with neurofibromatosis type 1, 11 Noonan syndrome and 3 Bannayan-Riley-Ruvalcaba syndrome. 8 patients reported a history of invasive infections requiring hospitalization and intravenous antibiotic therapy. Only 3 patients reported a history of unusual, difficult-to-treat or deep-seated infection. Adenotonsillectomy was performed in 11 patients (24%). However, in most cases (83%) patients' parents did not perceive their child as more prone to infections than their peers. Lymphocyte subpopulations were analyzed in 37 of the 47 patients (16 female, 21 males, age 1–40 years). Among the studied lymphocyte subsets, the only consistent alteration regarded an increased percentage of immature B cells (recent bone marrow emigrants) in 34 out of 37 (91,9%) patients, and an increased percentage of double negative T cells in 9 patients. In conclusion, although borderline immune abnormalities were present in a significant proportion of subjects and adenotonsillectomy was performed more frequently than expected for the general population, no major immune disturbance was found in this cohort of patients.

scholarly journals EXPRESS: Pulmonary Hypertension Associated With Neurofibromatosis Type 2

2021 ◽  
pp. 204589402110295
Author(s):  
Hirohisa Taniguchi ◽  
Tomoya Takashima ◽  
Ly Tu ◽  
Raphaël Thuillet ◽  
Asuka Furukawa ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Neurofibromatosis Type ◽  
Pulmonary Vascular Remodeling ◽  
Life Threatening ◽  
History Of ◽  
Pulmonary Arterial ◽  
First Time

Although precapillary pulmonary hypertension (PH) is a rare but severe complication of patients with neurofibromatosis type 1 (NF1), its association with NF2 remains unknown. Herein, we report a case of a 44-year-old woman who was initially diagnosed with idiopathic pulmonary arterial hypertension (IPAH) and treated with PAH-specific combination therapy. However, a careful assessment for a relevant family history of the disease and genetic testing reveal that this patient had a mutation in the NF2 gene. Using immunofluorescence and Western blotting, we demonstrated a decrease in endothelial NF2 protein in lungs from IPAH patients compared to control lungs, suggesting a potential role of NF2 in PAH development. To our knowledge, this is the first time that precapillary PH has been described in a patient with NF2. The altered endothelial NF2 expression pattern in PAH lungs should stimulate work to better understand how NF2 is contributing to the pulmonary vascular remodeling associated to these severe life-threatening conditions.

Brain metastasis of Wilms tumor with diffuse anaplasia and complex cytogenetic phenotype in a child with neurofibromatosis Type 1

2011 ◽  
Vol 8 (4) ◽  
pp. 353-356
Author(s):  
Marianna Shvartsbeyn ◽  
Luigi Bassani ◽  
Irina Mikolaenko ◽  
Jeffrey H. Wisoff
Keyword(s):  
Brain Metastasis ◽  
Neurofibromatosis Type 1 ◽  
Wilms Tumor ◽  
Metastatic Tumor ◽  
Neurofibromatosis Type ◽  
Radiological Features ◽  
First Case ◽  
History Of ◽  
The Brain

The authors report the first case of a Wilms tumor (WT) with diffuse anaplasia metastatic to the brain in a 13-year-old girl with a history of neurofibromatosis Type 1. At presentation, the metastatic tumor had radiological features that suggested a meningioma. Histologically it was characterized by striking anaplasia and features similar to the patient's previously resected WT with diffuse anaplasia.

scholarly journals Multiple Gastric Gastrointestinal Stromal Tumors in a Patient with Neurofibromatosis Type 1

2016 ◽  
Vol 2016 ◽  
pp. 1-5
Author(s):  
Makoto Tomatsu ◽  
Jun Isogaki ◽  
Takahiro Watanabe ◽  
Kiyoshige Yajima ◽  
Takuya Okumura ◽  
...  
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Gastrointestinal Stromal Tumors ◽  
Kinase Inhibitor ◽  
Submucosal Tumor ◽  
Neurofibromatosis Type ◽  
Stromal Tumors ◽  
Serosal Surface ◽  
History Of ◽  
Small Intestinal

Gastrointestinal stromal tumors (GISTs) are relatively common in neurofibromatosis type 1 (NF 1) patients. Approximately 90% of GISTs associated with NF 1 are located in the small intestine, while sporadic GISTs are most commonly located in the stomach. Here we report an extremely rare case of an NF 1 patient with multiple gastric GITs (90 or more) but without multiple small intestinal tumors. A 63-year-old female patient who had a history of NF 1 underwent surgery for a gastric neuroendocrine tumor and gastric submucosal tumor (SMT). During the operation, multiple small nodules were identified on the serosal surface of the upper stomach. SMT and multiple nodules on the serosal surface were diagnosed as GISTs consisting of spindle cells positive for KIT, CD34, and DOG-1. Both GIST and the normal gastric mucosa showed no mutations not only in the c-kitgene (exons 8, 9, 11, 13, and 17) but also in thePDGFRAgene (exons 12, 14, and 18). This patient is being followed up without the administration of a tyrosine kinase inhibitor.

Mosaic Generalized Neurofibromatosis 1: Report of Two Cases

2014 ◽  
Vol 18 (4) ◽  
pp. 271-274 ◽  
Author(s):  
Jori Hardin ◽  
Allan Behm ◽  
Richard M. Haber
Keyword(s):  
Somatic Mutations ◽  
Clinical Phenotype ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis 1 ◽  
Limited Disease ◽  
Disease Mutations ◽  
Single Region ◽  
History Of

Background: We report two cases of mosaic generalized neurofibromatosis 1 (NF1) and review the history of the classification of segmental neurofibromatosis (SNF; Ricardi type NF-V). Somatic mutations giving rise to limited disease, such as segmental neurofibromatosis are manifestations of mosaicism. If the mutation occurs before tissue differentiation, the clinical phenotype will be generalized disease. Mutations that occur later in development give rise to disease that is confined to a single region. Objectives: Segmental neurofibromatosis is caused by a somatic mutation of neurofibromatosis type 1, and should not be regarded as a distinct entity from neurofibromatosis 1. Cases previously referred to as unilateral or bilateral segmental neurofibromatosis are now best referred to as mosaic generalized or mosaic localized neurofibromatosis 1.

scholarly journals Case Report: Chemotherapy Indication in a Case of Neurofibromatosis Type 1 Presenting Optic Pathway Glioma: A One-Year Clinical Case Study Using Differential Tractography Approach

2021 ◽  
Vol 15 ◽  
Author(s):  
Amir Mohammad Pajavand ◽  
Guive Sharifi ◽  
Amir Anvari ◽  
Farahnaz Bidari-Zerehpoosh ◽  
Mohammad A. Shamsi ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Neurofibromatosis Type 1 ◽  
Clinical Case ◽  
Neurofibromatosis Type ◽  
Statistical Analyses ◽  
Optic Pathway Glioma ◽  
Clinical Case Study ◽  
Over Time

Neurofibromatosis type 1 (NF1) is associated with peripheral and central nervous system tumors. It is noteworthy that the regions in which these tumors frequently arise are the optic pathways (OPs) and the brainstem. Thus, we decided to trace the procedure of diffusion Magnetic Resonance Imaging (dMRI) alterations along with Short-Wavelength Automated Perimetry (SWAP) examinations of the OPs after surgery and chemotherapy over 1 year, which enabled us to evaluate chemotherapy's efficacy in an NF1 patient with an OP tumor. In this study, a 25-year-old woman with NF1 and left optic radiation (OR) glioma underwent surgery to remove the glioma. Immunohistochemistry (IHC) revealed a Pilocytic Astrocytoma (PA) WHO grade I. Post-operation chemotherapy done using nine treatment cycles of administering Temozolomide (TMZ) for 5 days every 4 weeks. Applying the region of interest (ROI) differential tractography method and SWAP four times every 3 months allowed us to follow the patient's visual acuity alterations longitudinally. The differential deterministic tractography method and statistical analyses enabled us to discover the white matter (WM) tracts anisotropy alterations over time. Furthermore, statistical analyses on the SWAP results along time illustrated possible alterations in visual acuity. Then, we could compare and associate the findings with the SWAP examinations and patient symptoms longitudinally. Statistical analyses of SWAP tests revealed a significant improvement in visual fields, and longitudinal differential tractography showed myelination and dense axonal packing in the left OR after 1 year of treatment. In this study, we examined an old hypothesis suggesting that chemotherapy is more effective than radiotherapy for NF1 patients with OP gliomas (OPGs) because of the radiation side effects on the visual field, cognition, and cerebrovascular complications. Our longitudinal clinical case study involving dMRI and SWAP on a single NF1-OPG patient showed that chemotherapy did not suppress the OP myelination over time. However, it should be noted that this is a clinical case study, and, therefore, the generalization of results is limited. Future investigations might focus on genetic-based imaging, particularly in more cases. Further, meta-analyses are recommended for giving a proper Field Of View (FOV) to researchers as a subtle clue regarding precision medicine.

scholarly journals A Rare Case of Hypophosphataemic Osteomalacia in von Recklinghausen Neurofibromatosis

2021 ◽  
Author(s):  
Yasmine Makhlouf ◽  
Soumaya Boussaid ◽  
Houda Ajlani ◽  
Samia Jemmali ◽  
Sonia Rekik ◽  
...  
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Fibroblast Growth Factor 23 ◽  
Neurofibromatosis Type ◽  
High Dose ◽  
Rare Tumour ◽  
Appropriate Treatment ◽  
History Of ◽  
Von Recklinghausen ◽  
Hypophosphataemic Osteomalacia

Background: Neurofibromatosis type 1 (NF1), also known as von Recklinghausen disease, is a one of the more common hereditary autosomal disorders. However, osteomalacia in neurofibromatosis type 1 is very rare tumour-induced osteomalacia; fibroblast growth factor-23 is usually implicated. Patients and methods: We report the case of a patient with a history of von Recklinghausen neurofibromatosis who presented with hypophosphataemic osteomalacia. Results: The patient was treated with high-dose calcitriol and oral phosphate with clinical improvement. Conclusion: Even though it is a rare entity, we must consider the diagnosis of hypophosphataemic osteomalacia in patients with neurofibromatosis in order to deliver appropriate treatment.

Sign in / Sign up

Export Citation Format

Share Document