[Neurofibromatosis type 1 - description of clinical features and molecular mechanism of the disease]

Abstract

Neurofibromatosis type 1 (NF1) called also von Recklinghausen's disease is an autosomal dominant genetic disorder with a complex clinical course. Clinical signs and symptoms concern mainly skin (with pigmentation abnormalities- café au lait macules, axillary/groin freckling and neurofibromas) and central nervous system (cognitive impairment, epilepsy, attention deficit hyperactivity disorder and gliomas). However, pathologic changes may also affect other organs and systems, including skeletal system (scoliosis, hypostature, osteoporosis, pseudoarthrosis and sphenoid wing dysplasia) or cardiovascular system (hypertension, inherited cardiovascular malformations). Another characteristic abnormality, which is an important diagnostic criterion of the disease, is the presence of Lisch nodules- hamartomatic changes of the iris. The development of NF1 is a consequence of inactivation of NF1 gene. The gene, located on chromosome 17, has one of the greatest frequencies of spontaneous mutation in the whole human genome. Gene product, a cytoplasmic protein called neurofibromin, is a tumor suppressor, with expression detected in various cells, mainly in malanocytes, neurons, Schwann cells and glial cells. Due to its anti-tumoral function, inactivation of NF1 protein leads to the growth of several neoplasms, concerning mainly skin and central nervous system (CNS). Skin tumors are actually malignances of the peripheral nervous system (PNS) and include cutaneous, subcutaneous and plexiform neurofibromas. In the CNS the most frequently occurring tumors are gliomas located in the optic pathway, followed by those developing in other parts of CNS. Histologically, CNS tumors are usually a benign pilocytic astrocytoma, consisting of malignant-transformed astrocytes.