Handbook of Genetic Counseling/Neurofibromatosis - Type 2
Neurofibromatosis - Type 2
ContractingEdit
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EtiologyEdit
- Disease characteristics
- Genetic disorder that causes tumors to grow on various nerves
- Also affects other tissues such as bones and skin
- Two distinct types: NF-1 and NF-2
- Inheritance
- Autosomal dominant
- Affected individuals have 50% chance of passing on mutation to each of their children
- Half of affected individuals have de novo mutations
- If neither parent has NF2, recurrence risk is very low - only one case of germline mosaicism reported
- Uniform age of onset within families
- Molecular genetics
- Caused by mutation in the NF2 gene
- Located at 22q12
- Normal gene product is schwannomin or merlin
- Homology to 4.1 family of cytoskeletal associated proteins
- Has role in prevention of schwannoma formation
- Tumor suppressor gene
- Incidence is 1 in 40,000 people
Clinical Features and Natural HistoryEdit
- Some variability in clinical manifestations
- Variability within families is low
- Suggests strong genotype-phenotype correlation
- Average age of onset of symptoms is 18-24
- Some people don't develop signs until their 40's or 50's
- Considered adult-onset so may be underdiagnosed in children
- Nonsense and frame shift mutations more severe
- Bilateral vestibular schwannoma (acoustic neuroma)
- Affect almost all patients with NF2
- Tumor that arises from Schwann cells that support and protect nerves with insulation needed to conduct information on 8th cranial nerve
- Initial symptoms include tinnitus (ringing in ears), hearing loss, and balance dysfunction
- May result in hearing loss in one or both ears
- Spinal tumors (>66%)
- Include schwannomas that may cause numbness in part of body
- Intramedullary tumors such as astrocytoma and ependymoma (5-33%)
- Most individuals with spinal cord tumors have more than one
- Meningiomas (50%)
- Tumor that grows from cells that line the brain and spinal cord in protective sheets called meninges
- May be intracranial or spinal
- Cause different neurological symptoms depending on location
- Ocular involvement (33%)
- Cataracts
- Known as juvenile posterior sublenticular opacity
- May impair vision if not removed
- Optic gliomas
- Tumors on vision nerve
- May lead to blindness
- Cataracts
- Other features
- Other types of central nervous system tumors
- Atypical café-au-lait spots
- Cutaneous neurofibromas
- Somatic mosaicism
- Suspected in individuals with unilateral vestibular schwannoma and multiple other tumors on one side
- More difficult to diagnose
- Considerably shortened lifespan
- Average age of death is 36 years
- With improvements in diagnosis, monitoring, and surgery this is changing
Diagnosis/Testing OptionsEdit
- Clinical diagnosis
- Bilateral VIII nerve mass on CT or MRI (vestibular schwannomas)
OR
- First degree relative with NF2 and either
- Unilateral 8th nerve mass
- First degree relative with NF2 and either
OR
- Two of the following
- Meningioma
- Glioma
- Schwannoma
- Juvenile posterior subcapsular lenticular opacity
- Two of the following
- Mutation analysis
- Mutations identified in 65-80% of patients with clinical diagnosis
- Testing provided by Athena Diagnostics/Mass Gen
- Includes SSCP (single stranded conformational polymorphism)
- May take up to 6 months for results
- Costs about $2700
- Considered appropriate to test unaffected at risk children and adults
- Linkage analysis
- Appropriate if more than one affected family member
- Doesn't work for 50% of patients with de novo mutations
- High accuracy because markers are very closely linked
- Prenatal testing
- Available for fetuses at 50% risk or greater
- Can be performed if mutation identified in affected family member
- Requires cells obtained from CVS or amniocentesis
ManagementEdit
- Currently is no cure or treatment
- Early recognition allows for earlier intervention and improved outcome
- Begin screening in early teens
- ABR and MRI exams for vestibular schwannomas
- Surgery generally successfully preserves hearing is tumors small
- Should begin learning sign language before hearing is lost
- Hearing aids may help preserve hearing early on
- Routine complete eye examinations
- Routine neurological examinations
- Intracranial, cranial nerve, and spinal tumors often slow growing
- ABR and MRI exams for vestibular schwannomas
Differential DiagnosisEdit
- NF1
- Has Lisch nodules, axillary and inguinal freckling, and plexiform neurofibromas not seen in NF2
- Patients with NF2 do not have mental retardation or learning problems
- Unilateral vestibular schwannoma
- Accounts for 5-10% of intracranial tumors
- Less than 5% are bilateral and associated with NF-2
- Schwannomatosis
- Multiple schwannomas without vestibular schwannomas
- Develop intracranial, spinal nerve root, or peripheral nerve tumors
- Multiple meningiomas
- Without vestibular schwannomas
- Typically occur in older adults
Psychosocial IssuesEdit
- Feelings of fear, anger, shock, denial over new diagnosis
- Difficulty adjusting to loss of hearing
- Burden of condition requiring extensive surveillance
- Anxiety about possibility of shortened life span
- Survivor guilt, transmitter guilt
- Support system to help cope with diagnosis
Support ResourcesEdit
- National Neurofibromatosis Foundation
- 95 Pine Street, 16th Floor
- New York, NY 10005
- Phone: 800-323-7938
- Web: www.nf.org
- Neurofibromatosis, Inc
- 8855 Annapolis Road, Suite 110
- Lanham, MD 20706-2924
- Phone: 410-461-5213
- Web: www.nfinc.org
- The Acoustic Neuroma Association
- PO Box 12402
- Atlanta, GA 30355
- Phone: 404-237-2704
- Web: ANAUSA@aol.com
ReferencesEdit
- GeneReviews. "Neurofibromatosis 2" (2002).
- "Neurofibromatosis Type 2: Information for Patients and Families." National Neurofibromatosis Foundation brochure.
NotesEdit
The information in this outline was last updated in 2001.