Abstract
Neurofibromatosis type 1 is defined clinically and molecularly by the presence of a mutation in neurofibromin, resulting in typical cutaneous, peripheral nerve and nerve root neurofibromas through the changes in regulation of the RAS pathway. A 33-year-old right-handed African-American female presented with a complaint of back pain, radiating down the legs and arms worsening over several years. On physical exam, the patient had no cutaneous neurofibromas, café-au-lait spots, or axillary freckling. MRI spine revealed diffuse symmetric fusiform nerve sheath tumors throughout the cervical, thoracic, and lumbar spine favored to represent neurofibromatosis. Genetics evaluation with pedigree revealed no family history of genetic disorders. Genetic testing was positive solely for a c.293A >G transition in exon 5 of the RIT1 gene, previously reported as a cause of the RASopathy Noonan syndrome, type-8. RASopathies are conditions caused by mutations in the proteins of the RAS-MAPK pathway. Noonan Syndrome can present with some combination of abnormalities of the ears, webbing of the neck, developmental delay, and cardiac abnormalities. This patient was without external phenotypic characteristics of Noonan Syndrome, yet was found to have a mutation in this pathway. RIT1 mutation has been previously described rarely with glioma development. Alternate mutations in the RAS-MAPK pathway should be considered in the differential for patients with spinal neurofibromatosis when typical neurofibromatosis mutations are absent.
Juvenile papillomatosis of the breast and family history of breast carcinoma