Makindo Medical Notes

Related Subjects: |Autosomal Dominant |Autosomal Recessive |X Linked Recessive |Neurofibromatosis Type 1 |Neurofibromatosis Type 2

There are at least two mechanisms for secondary hypertension in patients with Neurofibromatosis Type 2 (NF2) — Phaeochromocytoma and Renal artery stenosis.

About

• Neurofibromatosis Type 2 (NF2) is a genetic disorder characterized by the development of benign tumors, especially affecting the nervous system.
• It is autosomal dominant and affects approximately 1 in 40,000 individuals.
• NF2 is much less common than Neurofibromatosis Type 1 (NF1).
• There is often a family history of NF2, though some cases arise from de novo mutations.

Aetiology

• The NF2 gene is located on chromosome 22, encoding a tumor suppressor protein called **Merlin** (also known as Schwannomin).
• Merlin is involved in maintaining the structure of the cytoskeleton and preventing uncontrolled cell growth, particularly in nerve cells.
• Loss of function of the NF2 gene leads to the development of various tumors in the central and peripheral nervous systems.

Clinical Features

• Bilateral Vestibular Schwannomas (Acoustic Neuromas): These are the hallmark of NF2 and can lead to hearing loss, tinnitus, and balance issues due to involvement of the eighth cranial nerve.
• Juvenile posterior subcapsular lenticular opacity: A cataract that occurs at an early age, leading to potential blindness.
• Other brain and spinal cord tumors such as meningiomas, ependymomas, astrocytomas, and gliomas are frequently observed in NF2 patients.
• Spinal tumors like intramedullary gliomas and ependymomas occur with increased frequency.
• Cutaneous features: Though less pronounced than in NF1, patients may develop cutaneous neurofibromas and subcutaneous nodules.
• Other clinical signs include plexiform neuromas and optic nerve gliomas, which may lead to vision loss.

Associations

• Pulmonary Fibrosis: A rare but recognized complication in NF2.
• Hypertrophic Cardiomyopathy: Cardiac involvement in some patients.
• Skeletal Abnormalities: Scoliosis and local gigantism of a limb may be seen.
• Secondary Hypertension: May occur due to Phaeochromocytoma or Renal artery stenosis.
• Orbital Haemangiomas: Benign vascular lesions affecting the orbit, potentially leading to visual impairment.

Management

• Supportive Care: Given the chronic nature of the disease, management is focused on symptom control and addressing specific complications such as hearing loss, visual impairment, and tumor growth.
• Regular Monitoring: MRI is the preferred imaging modality for monitoring brain, spine, and peripheral nerve tumors.
• Auditory Brainstem Implants (ABI): These may be considered in cases of severe hearing loss due to bilateral vestibular schwannomas.
• Genetic Counseling: NF2 is inherited in an autosomal dominant pattern, so genetic counseling is important for affected families.
• Secondary Hypertension Management: Screen for Phaeochromocytoma and Renal artery stenosis if secondary hypertension is suspected. Treat appropriately with antihypertensives and possible surgical intervention for Phaeochromocytoma.

References

• Neurofibromatosis Type 2 - Genetics Home Reference
• Neurofibromatosis Type 2 Information - NORD