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

Neurofibromatosis Type I and Stromal Tumor with a Multiple Digestive Localization

Neurofibromatosis type I (NF1) is also known as von Recklinghausen disease. It is a genetic disorder that affects the growth and development of nerve cell tissue, which is characterized by a multisystem disorder and an increased risk for cancer. The incidence of gastroduodenal stromal tumor during Recklinghausen disease can reach 35% in autopsies and 5% in clinical cases. In our case, the diagnosis of neurofibromatosis type I was made in a middle-aged women initially diagnosed with a pancreaticoduodenal tumor.

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.

A Child Presented with Clitoromegaly in Context with Neurofibromatosis Type 1

Neurofibromatosis type 1, also called Von Recklinghausen Disease is a genetic disorder characterized by the development of multiple benign tumors affecting the skin and nervous system. It is a genetic disease with a prevalence of one case in 3000 births. The cause of VRD is a genetic mutation [1-4]. In half of all cases of NF1, the faulty gene is passed from a parent to their child. Clitoromegaly presenting in childhood can be congenital or acquired. Nonhormonal causes like NF1, epidermoid cysts, tumor syndromes have been reported [5]. Clitoris enlargement is a frequently seen congenital malformation, but acquired clitoral enlargement is rarely detected. While most cases of VRD are the result of a genetic mutation in the neurofibromin gene, there are also acquired cases due to spontaneous mutations [4]. The pathological alterations behind it begin in the embryonic period, prior to differentiation of the neural crest. We report a case of 6.5 year - old - female admitted for clitoromegaly and an apparent deformity of the genital organs. The girl has been diagnosed with clitoromegaly in the context of NF1 Disease. This patient was successfully treated by clitoroplasty. The biopsied clitoral tissue was sent to pathology and revealed plexiform neurofibroma.

Satisfaction from surgical treatment and its’ influence on comfort of feeling in patients with Recklinghausen disease

Background. Neurofibromatosis type 1 (NF-1) is one of the most common autosomal dominant disorders. Multiple benign dermal neurofibromas, cafe´ au lait spots, axillary and inguinal freckling are the hallmarks of NF1. Aim. The aim of this paper is to verify if surgical treatment performed in patients with NF-1 is satisfactory for them and to describe demographic factors characteristic to patients with Recklinghausen disease. Methods. A special questionnaire was prepared for the study, which contained 45 questions. Seventeen patients with neurofibromatosis type 1 agreed to fill in the questionnaire aged from 22 to 61 years. Results. Surgical treatment in patients was started between 6 and 45 years of age. All patients declare their will to continue surgical treatment. After treatment patients think that they are more comfortable, more self-confident and sociable. The first symptoms of neurofibromatosis were seen in about 13 years of life in most patients. In the group of women who gave a birth all of them noticed progression of the disease during pregnancy. Conclusions. Performed surgical treatment raises life comfort and increase self-confidence in patients with neurofibromatosis type 1. Due to visibility of neurofibromas it is worth to refer patients to Department of Plastic Surgery. Doctors dealing with patient with NF-1shoud inform them about its inheritance basis and that puberty and pregnancy intensify the process of skin neurofibroma development.