von Recklinghausen's Disease


von Recklinghausen's Disease also called Neurofibromatosis is a genetic disorder of the nervous system. It mainly affects how nerve cells form and grow. It causes tumors to grow on nerves. You can get neurofibromatosis from your parents, or it can happen because of a mutation (change) in your genes. Once you have it, you can pass it along to your children

There are three types of neurofibromatosis:
  • Type 1 (NF1) causes skin changes and deformed bones and usually starts at birth.
  • Type 2 (NF2) causes hearing loss, ringing in the ears and poor balance. It often starting in the teen years.
  • Schwannomatosis causes intense pain. It is the rarest type.
There is no cure. Treatment is aimed at controlling symptoms. Depending on the type of disease and how bad it is, treatment may include surgery to remove tumors, radiation therapy and medicines.

Neurofibromatosis type 1

Neurofibromatosis type 1 is a condition characterized by changes in skin coloring (pigmentation) and the growth of tumors along nerves in the skin, brain, and other parts of the body. The signs and symptoms of this condition vary widely among affected people.

Beginning in early childhood, almost all people with neurofibromatosis type 1 have multiple café-au-lait spots, which are flat patches on the skin that are darker than the surrounding area. These spots increase in size and number as the individual grows older. Freckles in the underarms and groin typically develop later in childhood.

Most adults with neurofibromatosis type 1 develop neurofibromas, which are noncancerous (benign) tumors that are usually located on or just under the skin. These tumors may also occur in nerves near the spinal cord or along nerves elsewhere in the body. Some people with neurofibromatosis type 1 develop cancerous tumors that grow along nerves. These tumors, which usually develop in adolescence or adulthood, are called malignant peripheral nerve sheath tumors. People with neurofibromatosis type 1 also have an increased risk of developing other cancers, including brain tumors and cancer of blood-forming tissue (leukemia).

During childhood, benign growths called Lisch nodules often appear in the colored part of the eye (the iris). Lisch nodules do not interfere with vision. Some affected individuals also develop tumors that grow along the nerve leading from the eye to the brain (the optic nerve). These tumors, which are called optic gliomas, may lead to reduced vision or total vision loss. In some cases, optic gliomas have no effect on vision.

Additional signs and symptoms of neurofibromatosis type 1 include high blood pressure (hypertension), short stature, an unusually large head (macrocephaly), and skeletal abnormalities such as an abnormal curvature of the spine (scoliosis). Although most people with neurofibromatosis type 1 have normal intelligence, learning disabilities and attention deficit hyperactivity disorder (ADHD) occur frequently in affected individuals.

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Neurofibromatosis type 2

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 or acoustic neuromas. These growths develop along the nerve that carries information from the inner ear to the brain (the auditory nerve). Tumors that occur on nerves in other areas of the brain or spinal cord are also commonly seen with this condition.

The signs and symptoms of this condition usually appear during adolescence or in a person's early twenties, although onset can occur at any age. The most frequent early symptoms of vestibular schwannomas are hearing loss, ringing in the ears (tinnitus), and problems with balance. In most cases, these tumors occur in both ears by age 30. If tumors develop in other parts of the brain or spinal cord, signs and symptoms vary according to their location. Complications of tumor growth can include changes in vision or sensation, 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.

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Genes related to neurofibromatosis type 1 & type 2

Mutations in the NF1 gene cause neurofibromatosis type 1.

The NF1 gene provides instructions for making a protein called neurofibromin. This protein is produced in many cells, including nerve cells and specialized cells surrounding nerves (oligodendrocytes and Schwann cells). Neurofibromin acts as a tumor suppressor, which means that it keeps cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in the NF1 gene lead to the production of a nonfunctional version of neurofibromin that cannot regulate cell growth and division. As a result, tumors such as neurofibromas can form along nerves throughout the body. It is unclear how mutations in the NF1 gene lead to the other features of neurofibromatosis type 1, such as café-au-lait spots and learning disabilities.

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 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. Mutations 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.

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Inheritance of neurofibromatosis type 1 & type 2

Neurofibromatosis type 1 is considered to have an autosomal dominant pattern of inheritance. People with this condition are born with one mutated copy of the NF1 gene in each cell. In about half of cases, the altered gene is inherited from an affected parent. The remaining cases result from new mutations in the NF1 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 NF1 gene must be altered to trigger tumor formation in neurofibromatosis type 1. A mutation in the second copy of the NF1 gene occurs during a person's lifetime in specialized cells surrounding nerves. Almost everyone who is born with one NF1 mutation acquires a second mutation in many cells and develops the tumors characteristic of neurofibromatosis type 1.

Neurofibromatosis type 2 is considered to have an autosomal dominant pattern of inheritance. People with this condition are born with one mutated 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 mutations 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 mutation 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 mutation acquires a second mutation in many cells and develops the tumors characteristic of neurofibromatosis type 2.

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Complications of NF1
    Disfigurement
    NF1 can result in disfigurement in a number of ways. Skin neurofibromas may develop on the face or on exposed areas of the arms or legs. The generally larger and deeper plexiform neurofibromas may grow around the eye or eyelid, or affect growth of one side of the face. Scoliosis, or curvature of the spine (see below), can affect appearance when it is severe. Growths can occur around the nipple (periareolar neurofibromas) which may be distressing. Rarely, an overgrowth of skin or bone causes enlargement of an arm or leg.

    In some people, the size or number of neurofibromas increases during puberty and pregnancy, reflecting a possible hormonal effect.

    Scoliosis
    Lateral curvature of the spine, known as scoliosis, is common in NF1. In most cases it is mild. Scoliosis usually appears in early childhood. A child with scoliosis will need periodic spine X-rays and physical examinations to determine whether corrective measures are needed. In some cases, a brace may be used to prevent progression of the problem. More serious cases may require corrective surgery.

    Learning Disabilities
    Learning disabilities, often first noticed when the child starts school, are specific problems with reading, writing and the use of numbers which occur in children who have normal intelligence. Learning disabilities are more common in children with NF1 than in other children, and may be associated with hyperactivity. A child suspected of having a learning disability can be evaluated by a psychologist, child neurologist or professional with special knowledge of this problem. Many school systems provide referrals to specialists in these fields.

    Large Heads
    Children and adults with NF1 often have large head circumference, which usually does not indicate any significant medical problem. Very rarely, large head circumference results from hydrocephalus, a serious problem which may require surgery. Imaging of the brain with CT scan or MRI can help determine if head enlargement is serious or not. Head circumference in children with NF1 should be measured periodically.

    Optic Gliomas
    An optic glioma is a tumor of the optic nerve (the nerve which controls vision). This tumor, which fortunately is uncommon, usually appears in childhood and is first noticed because of poor or failing vision or bulging of the eye. Children with NF1 should have routine eye examinations by an ophthalmologist, neurologist or physician familiar with this problem. Treatment for this condition includes surgery and radiation therapy.

    Congenital Defects of Bone
    The variety of bone defects seen in NF1 are usually evident at birth. Most are uncommon. Defects can occur in almost any bone, but are seen most often in the skull and limbs. They include:
  • Congenital absence of the orbital wall, the bone normally surrounding the eye. Its absence may cause slight bulging of the skin around the eye.
  • Bowing of the leg bones below the knee (tibia or fibula). These bones may be thinner than normal and bowed. If a fracture occurs, healing may be slow or incomplete. Incomplete healing, called pseudarthrosis, may also affect the bones in the forearm (radius or ulna), but this occurs very rarely. This is a difficult problem, which requires the supervision of an orthopedic surgeon.


    • High Blood Pressure (Hypertension)
    People with NF1 can have hypertension for reasons completely unrelated to NF1. However, two rare problems associated with NF1 may result in hypertension: renal artery stenosis (blockage of the artery to the kidney), and pheochromocytoma, a rare and usually benign tumor of the adrenal gland. Both of these problems are treatable. Because of these possible problems, it is important that routine physical exams for children and adults with NF1 include blood pressure checks.

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Complications of NF2

The early symptoms of NF2 are symptoms of dysfunction of the acoustic (hearing) nerve, which carries information about sound to the brain, and the vestibular nerve, which carries balance information to the brain. Consequently, hearing loss, ringing in the ears (called tinnitus) and problems with balance, beginning in the teens or early twenties, are generally the first symptoms of NF2.

Other symptoms of NF2 may include facial weakness, headache, change in vision, and a lump or swelling under the skin caused by the development of a neurofibroma. In a family member at risk for NF2, a positive diagnosis is suspect if mild signs of NF are found elsewhere, such as 1 or 2 café-au-lait spots or a small lump under the scalp or skin.

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Information obtained from National Institute of Health
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