Neurofibromatosis type 2

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Neurofibromatosis type 2 is a disorder characterized by the growth of noncancerous tumors in the nervous system. The most common tumors associated with neurofibromatosis type 2 are called vestibular schwannomas. These growths develop along the nerve that carries information from the inner ear to the brain (the auditory nerve). Tumors that form on the membrane that covers the brain and spinal cord (meninges) are also common in neurofibromatosis type 2. These tumors are called meningiomas. Tumors can also occur on other nerves or tissues in the brain or spinal cord in people with this condition.

The signs and symptoms of neurofibromatosis type 2 usually appear during adolescence or in a person's early twenties, although they can begin at any age. The most frequent early symptoms of vestibular schwannomas are hearing loss, ringing in the ears (tinnitus), and problems with balance. Less commonly, vestibular schwannomas cause facial weakness or paralysis. In most cases, these tumors occur in both ears (bilaterally) by age 30. If tumors develop elsewhere in the nervous system, signs and symptoms vary according to their location. Complications of tumor growth can include changes in vision, numbness or weakness in the arms or legs, and fluid buildup in the brain. Some people with neurofibromatosis type 2 also develop clouding of the lens (cataracts) in one or both eyes, often beginning in childhood.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Variants (also known as mutations) in the NF2 gene cause neurofibromatosis type 2. The NF2 gene provides instructions for making a protein called merlin (also known as schwannomin). This protein is produced in the nervous system, particularly in Schwann cells, which surround and insulate nerve cells (neurons) in the brain and spinal cord. Merlin acts as a tumor suppressor, which means that it keeps cells from growing and dividing too rapidly or in an uncontrolled way. Although its exact function is unknown, this protein is likely also involved in controlling cell movement, cell shape, and communication between cells. Variants in the NF2 gene lead to the production of a nonfunctional version of the merlin protein that cannot regulate the growth and division of cells. Research suggests that the loss of merlin allows cells, especially Schwann cells, to multiply too frequently and form the tumors characteristic of neurofibromatosis type 2.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Neurofibromatosis type 2 is considered to have an autosomal dominant pattern of inheritance. People with this condition are born with one altered copy of the NF2 gene in each cell. In about half of cases, the altered gene is inherited from an affected parent. The remaining cases result from new variants in the NF2 gene and occur in people with no history of the disorder in their family.

Unlike most other autosomal dominant conditions, in which one altered copy of a gene in each cell is sufficient to cause the disorder, two copies of the NF2 gene must be altered to trigger tumor formation in neurofibromatosis type 2. A variant in the second copy of the NF2 gene occurs in Schwann cells or other cells in the nervous system during a person's lifetime. Almost everyone who is born with one NF2 variant acquires a second variant (known as a somatic variant) in these cells and develops the tumors characteristic of neurofibromatosis type 2.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Neurofibromatosis type 2 has an estimated incidence of 1 in 33,000 people worldwide.

Which doctor should you see?

The suggested department for discussing Neurofibromatosis type 2 is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Neurofibromatosis type 2. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.