Neurofibromatosis Type 1

What is neurofibromatosis type 1?

Neurofibromatosis type 1 is a genetic condition characterised by skin pigment changes and tumours that grow 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 the colour of coffee with milk. 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 have neurofibromas, which are noncancerous (benign) tumours that are usually located on or just under the skin. These tumours may also occur in the spinal cord or along nerves elsewhere in the body. Some people with neurofibromatosis type 1 develop cancerous tumours that grow along nerves. These tumours, which usually develop in adolescence or adulthood, are called malignant peripheral nerve sheath tumours. People with neurofibromatosis type 1 also have an increased risk of developing other cancers, including brain tumours and leukaemia (cancer of blood-forming tissue).

During childhood, benign growths called Lisch nodules often appear in the coloured part of the eye (the iris). Lisch nodules do not interfere with vision. Another type of tumour, called an optic glioma, can occur on the nerve leading from the eye to the brain. These tumours are usually benign, but can cause reduced vision or total vision loss.

Additional signs and symptoms of neurofibromatosis type 1 include high blood pressure and skeletal abnormalities such as curvature of the spine (scoliosis). Most people with this condition have normal intelligence. Fewer than 10 percent are mentally retarded, but about half of affected children have learning disabilities.

In some cases, people have features of both neurofibromatosis type 1 and another genetic condition, Noonan syndrome. Noonan syndrome is characterised by distinctive facial features, short stature, heart defects, and skeletal abnormalities. The combination of signs and symptoms of these two conditions is sometimes called neurofibromatosis-Noonan syndrome. Other affected individuals have features of neurofibromatosis type 1 with developmental delay and a heart defect called pulmonic stenosis. Together, these signs and symptoms are known as Watson syndrome. Researchers believe that neurofibromatosis-Noonan syndrome and Watson syndrome are variants of neurofibromatosis type 1 because the conditions are usually caused by mutations in the same gene.

How common is neurofibromatosis type 1?

Neurofibromatosis type 1 occurs in 1 in 3,000 to 4,000 people.

What genes are related to neurofibromatosis type 1?

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 nerve cells and in specialized cells surrounding nerves (oligodendrocytes and Schwann cells). Neurofibromin acts as a tumour 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, tumours such as neurofibromas can form along nerves throughout the body. Researchers are not yet certain how mutations in the NF1 gene cause other features of neurofibromatosis type 1, such as café-au-lait spots.

How do people inherit neurofibromatosis type 1?

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 are the result of 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 tumour 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 tumours characteristic of neurofibromatosis type 1.

What other names do people use for neurofibromatosis type 1?

  • Neurofibromatosis 1
  • NF1
  • Peripheral Neurofibromatosis
  • Recklinghausen Disease, Nerve
  • von Recklinghausen Disease

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