Multiple Sclerosis and Neurofibromatosis type1: case report

INTRODUCTION: Neurofibromatosis type 1 (NF1) or Von Reckligausen disease is characterized by multiple café au-lait spots and skin neurofibromas, and is caused by abnormal activity of the tumor suppressor gene NF1. The association of neurofibromatosis with multiple sclerosis (MS) has been rarely described, more frequently in patients with primary progressive MS. CASE REPORT: We describe a 36 year old woman diagnosed with Neurofibromatosis type 1 in childhood. She showed congenital cafè-au-lait spots, Lisch nodules of the iris, axillary freckles and cutaneous neurofibromas. At the age of 27, as part of investigations related to the underlying disease, she performed a brain MRI, which showed focal demyelination. At the age of 34 she developed paresthesias to the right emisoma and right-hand dystonia. The brain and cervical spine MRI showed demyelinating areas both in the brain and in the spinal cord. Two oligoclonal bands were found in the CSF. Blood and CSF examination for other autoimmune diseases (Behcet's disease, Sjogren's syndrome, Sarcoidosis, SLE, Lyme disease) and infectious diseases (like Brucellosis, Syphilis, HTLV-1 infection and herpes zoster) were negative. The patient recovered with intravenous steroid administration and at the age of 35 she started treatment with glatiramer acetate. Since then she had no relapses or new lesions at MRI scan. DISCUSSION: Genetic association between NF1 and MS has been hypothesized, focusing on OMGP-gene (oligodendrocyte-myelin glycoprotein gene), an intron of NF1 gene whose product is a CNS myelin protein and on NF1, which codes for neurofibromin, a protein that regulates cellular proliferation and differentiation. Mutations in NF1 would determine uncontrolled cellular proliferation of Schwann cells with an autoimmune response to oligodendrocytes antigens expressed in the central nervous system (CNS). NF and MS association is still debated since a causal relationship between the two diseases is not yet clearly defined.