Factsheet
Condition:
Neurofibromatosis
Inheritance:
Autosomal dominant
Genetic Etiology:
NF1: mutation in NF1 gene on chromosome 17; NF2: mutation in NF2 gene on chromosome 22. The NF1 gene product is neurofibromin, a GTPase activating protein; the NF2 gene product is called merlin or schwannomin. Both the NF1 and NF2 genes function as tumor suppressors.
Frequency:
NF1: 1/3,500; NF2: 1/40,000
Clinical features:
Both disorders are associated with development of tumors of the nerve sheath. In NF1 these are neurofibromas, whereas in NF2 they are schwannomas. Other features of NF1 include café-au-lait spots, intertriginous freckling, skeletal dysplasia, optic glioma, learning disability, and increased risk of malignancy or vascular disease. NF2 is associated with bilateral vestibular schwannomas, schwannomas of other cranial and spinal nerves, meningiomas, ependymomas, and posterior subcapsular cataract.
Management:
Screening for associated tumors and symptomatic treatment.
Genetic counseling:
Affected individuals at 50% risk of transmitting a gene mutation; both familial and de novo cases occur. Genetic testing is available, though not all pathogenic mutations can be identified. Penetrance is complete for both disorders.