Neurofibromatosis is inherited in an autosomal dominant fashion. It occurs in approximately 1/2000 individuals. While diagnosis is primarily made on a clinical basis, confirmation by molecular methods is available. Approximately 80% of individuals who fulfill the diagnosis of NF1 have an abnormality in protein truncation studies. A deletion of chromosome 22 can also be used for diagnosis. However only 5% of patients with NF1 have an identifiable deletion. Gene sequencing can detect up to 95% of the mutations in the NF1 gene. This testing is not currently available in the U.S.

In order to fulfill the diagnosis for NF1 an individual would need to have 2 or more of the following: 6 or more café au lait spots, 2 or more neurofibromas, axillary and/or inguinal freckling, Optic glioma, 2 or more Lisch nodules, or a first degree relative affected with NF1. The gene responsible for NF1 is located on chromosome 17. Approximately 50% of cases are new mutations and 50% are inherited from a parent. In order to be given the diagnosis of NF1, if there was no family history, an individual would need to have 2 features. If there is an affected parent, only 1 feature is needed to be given the diagnosis.

During infancy, some patients with NF1 have a fibular defect known as fibular dysplasia. Hydrocephalus is present in 1% of patients. Plexiform neuromas can also be one of the presenting symptoms of this disorder. They can be debilitating.

While all individuals with an abnormal gene present with characteristics, the severity can be variable among individuals within a family. The majority of patients with NF1 have only cutaneous features and Lisch nodules. More serious complications can increase with age. The total number of neurofibromas seen in adults with NF1 varies from a few to hundreds or even thousands. Additional cutaneous and subcutaneous neurofibromas continue to develop throughout life, although the rate of appearance may vary greatly from year to year. While the risk of malignant transformation is low, as the number of neurofibromas increases as so the risk of malignant transformation. Most individuals with NF1 have normal intelligence, but learning disabilities occur in about half of those with NF1.

Treatment of Neurofibromatosis I

Cutaneous or subcutaneous neurofibromas that are disfiguring or in inconvenient locations (e.g., at belt or collar lines) can be removed surgically. The disfigurement caused by NF1 is the most distressing disease manifestation for many individuals. Plexiform neurofibromas may grow to enormous size and can cause serious disfigurement, overgrowth, or impingement on normal structures. Surgical treatment of such lesions is often unsatisfactory because of their intimate involvement with nerves and the tendency of plexiform neurofibromas to grow back at the site of removal. Treatment of optic gliomas in individuals with NF1 is problematic. Because the optic gliomas in NF1 often spontaneously regress in NF1, many individuals with NF1 who develop optic nerve gliomas do not require treatment. Brain stem and cerebellar astrocytomas in individuals with NF1 may also follow a less aggressive course than in individuals without NF1. Occasional regression of these tumors in individuals with NF1 has also been reported.

An 18 year old male presents to clinic with hypertension. He is noted to have 10 café au lait spots greater then 1cmx1cm. He has axillary freckling.

  1. What medical exams would be important in determining the diagnosis?
  2. Is the hypertension related to the café au lait spots?
  3. What is the recurrence of this disorder in his future children?