Neurofibromatosis Type 1 and Type 2 Differences
Genetic Basis
- Neurofibromatosis type 1 (NF1) is caused by mutations in the NF1 gene located on chromosome 17, which encodes neurofibromin, a key negative regulator in the RAS-MAPK pathway 1, 3
- Neurofibromatosis type 2 (NF2) is caused by mutations in the NF2 gene located on chromosome 22, which encodes merlin (also called schwannomin) 1
- Both conditions are autosomal dominant disorders but affect approximately 1:25,000 persons for NF2 compared to 1:2,000-3,000 for NF1 1, 3
Hallmark Clinical Features
- Plexiform neurofibromas (often congenital but grow during the first two decades) are a hallmark of NF1 3
- Optic pathway gliomas (presenting early in childhood) are a common feature of NF1 3
- Bilateral vestibular schwannomas (VS) on the eighth cranial nerves are the defining feature of NF2 1, 4
- Multiple meningiomas are a common feature of NF2 1, 4
- Ependymomas and other central nervous system tumors can occur in NF2 1, 4
Diagnostic Criteria
- NF2 is primarily diagnosed by the presence of bilateral vestibular schwannomas, or can be diagnosed with a unilateral vestibular schwannoma plus at least two other NF2-related tumors 1, 4
Primary Morbidity and Mortality Concerns
- Optic pathway gliomas affecting vision are a concern in NF1 3
- Plexiform neurofibromas causing disfigurement and functional impairment are a concern in NF1 3
- Juvenile myelomonocytic leukemia, rhabdomyosarcoma, and neuroblastoma (rare but occur at higher frequencies than general population) are concerns in NF1 3
- Vestibular schwannomas causing hearing loss, tinnitus, and balance problems are a concern in NF2 1, 4
- Significant morbidity from surgical treatment of vestibular schwannomas, including deafness and facial nerve dysfunction, is a concern in NF2 1, 4
- Meningiomas causing neurological deficits depending on location are a concern in NF2 1, 4
Management Approaches
- Surveillance for optic pathway gliomas and other tumors is a management approach for NF1 3
- Management of plexiform neurofibromas, including emerging targeted therapies inhibiting the RAS-MAPK pathway, is a management approach for NF1 3
- Surgery is the primary clinical tool for management of vestibular schwannomas in NF2 1, 4
- Early interventional surgery may help preserve hearing in some cases of NF2 1
- Cochlear implants or auditory brainstem implants for hearing loss are a management option for NF2 1