Cervical and Spinal Plexiform Neurofibroma: A Case Report

Plexiform neurofibroma is a rare benign tumor of the peripheral nerves at the expense of perineural connective cells. It is pathognomonic of neurofibromatosis type 1 (NF1 or Von Recklinghausen disease). MRI is of great help in the diagnosis of this pathology. Anatomopathological confirmation is sometimes necessary, especially in the absence of a context suggestive of NF1. We report the observation of an oung boy with a cervical plexiform neurofibroma revealing a neurofibromatosis Type 1

LARGE PLEXIFORM NEUROFIBROMA OF THE SACRO-GLUTEAL REGION – A RARE CASE REPORT

Plexiform neurobroma is a rare benign nerve sheath tumor that develops in the perineurium and is often considered pathognomonic of neurobromatosis type 1 (NF1 or von Recklinghausen disease). They occur most frequently in the craniomaxillofacial region, rarely on back and extremities. These lesions are highly vascular and there is 15-20% potential for malignant transformation. Here, we present a 26-year-old female with neurobromatosis all over her body, but with a large plexiform neurobroma in the sacral region which was causing difculty in sitting and lying supine as well as disgurement of the gluteal region. Surgical excision with primary closure of the swelling was done. Histopathology ndings were consistent with neurobromatosis.

A Rare Case of Hypophosphataemic Osteomalacia in von Recklinghausen Neurofibromatosis

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.

The cryo-EM structure of the neurofibromin dimer reveals the molecular basis for von Recklinghausen disease

Neurofibromin (NF1) is a tumour suppressor mutated in neurofibromatosis type 1 (von Recklinghausen disease), one of the most common human genetic diseases(1). NF1 regulates cellular growth through suppressing the Rat Sarcoma (RAS) pathway and, accordingly, mutations in this protein drive numerous cancers, including melanoma, ovarian, breast and brain cancer(2, 3). Currently, however, the molecular basis for NF1 function remains to be understood. Here we address this problem and use cryogenic Electron Microscopy (cryo-EM) to determine the structure of fulllength NF1. The 640 kDa NF1 homodimer forms an extraordinary lemniscate (∞) shaped molecule that is ~30 nm in length and ~ 10 nm wide. Each NF1 monomer comprises an N-terminal HEAT-repeat domain (N-HEAT), a guanosine triphosphatase activating protein (GAP)-related domain (GRD), a Sec14 homologous and pleckstrin homologous module (SEC-PH), and a C-terminal HEAT domain (C-HEAT). The core NF1 scaffold is formed via a head-to-tail dimer of the N- and C-HEAT domains. This platform, which is responsible for interacting with more than 10 regulatory binding partners, comprises an extraordinary array of over 150 α-helices. Analysis of these EM data revealed that the GRD and SEC-PH domain are highly mobile with respect to the core scaffold and could not initially be accurately placed in electron density. Strikingly, however, using 3D variability analysis we were able to identify a significant subpopulation of NF1 particles and determine the complete NF1 structure to 5.6 Å resolution. These data revealed that the catalytic GRD and lipid binding SEC-PH domain are positioned against the core scaffold in a closed, autoinhibited conformation. We postulate that interaction with the plasma membrane may release the closed conformation in order to promote RAS inactivation. Our structural data further allow us to map the location of disease-associated NF1 variants and provide a long sought-after structural explanation for the extreme susceptibility of the molecule to loss-of-function mutations. Finally, it is suggested that approaches to combat NF1-linked diseases may include release of the autoinhibited state in order to improve NF1 catalytic efficiency.