Neurofibromatosis Type 1 (NF1)

Neurofibromatosis Type 1 is the most common form of the disease. It occurs in 1 in 3,000 to 4,000 births. This article mainly discusses NF1.

NF1 is also known as von Recklinghausen disease. It mainly affects nerves in the outer parts of the body. These nerves make up the peripheral nervous system.

Light-brown-colored birthmarks (café-au-lait spots) are a common sign of Neurofibromatosis Type 1 (NF1).

Symptoms begin at birth or early in life. People with NF1 may develop:

• Multiple birth marks. Six or more light-brown birthmarks, called cafe-au-lait spots, may occur anywhere on the body. The spots usually appear before about age 9. They have many shapes. In young children, they measure about 5mm or more. In teens, they measure 15mm or more.
  
  Other skin abnormalities in NF1 include freckles in the armpit and groin; these are called axillary and inguinal freckling.
• Multiple neurofibromas. These tumors are often small, painless, and slow-growing. They may form bumps on the skin or masses deep in the body. They can appear at any age but often first appear near adolescence.

Tumors caused by NF1 may affect the brain or spinal cord. They may grow on nerves of the eye, which is called an optic glioma). In rare cases, these tumors may affect vision.

At times, a tumor affects many nerves and grows very large; this is called a plexiform neurofibroma. It is most common on the face, arms, or legs. This tumor may be disfiguring, painful, or life-threatening and can also cause weakness in the arms or legs.

Most NF1 tumors are benign. However, a small number become cancerous.

Neurofibromas and café-au-lait spots in a patient with NF1.

Reproduced with permission from Crawford AH, Schorry EK: Neurofibromatosis in children: the role of the orthopaedist. J Am Acad Orthop Surg 1999; 7:217-230.

• Lisch nodules in the eyes. Lisch nodules are small brown tumors that often appear on the colored part of the eye, called the iris, in people with NF1. They cause no medical problems and may appear at about 6 to 10 years of age.
• Other complications. Learning disabilities affect many children with NF1. A child may learn to walk or talk later than usual. Some children also have:
  • Intellectual disability and/or speech problems
  • Short stature
  • An oversized head (macrocephaly)
  • Hypertension
  • An increased risk of cancer (malignancy)

NF1 can also cause orthopaedic problems, including bone abnormalities. The most common orthopaedic problems in children with NF1 include:

• Scoliosis. Scoliosis is a sideways curve of the spine. A normal spine forms a straight line down the middle of the back. A spine with scoliosis curves and may look like the letter S or C.
  
  Scoliosis curves in children with NF1 may be mild or severe. In many cases, the spinal curves get worse slowly. They change at about the same rate as curves in children with idiopathic scoliosis. This form of scoliosis in children with NF1 is called nondystrophic. However, the curve may change in severity and develop dystrophic changes.
  
  Dystrophic scoliosis is less common in children with NF1. In this form, the curve is short and sharp. It also occurs with kyphosis (rounding of the back). The ribs may become thin. The vertebrae may also form in an unusual way. This may be due to nerve root tumors or an enlarged dural sac within the vertebral canal. These curves can get worse fast and may cause a serious deformity.
  
  Children with NF1 may also have kyphosis as their main spinal deformity.

(Left) Normal spine anatomy. (Right) Scoliosis can make the spine look more like the letters "C" or "S."

• Congenital pseudarthrosis of the tibia. Neurofibromatosis Type 1 can cause unusual bone growth. The tibia, or shinbone, is affected most often. In a small number of children with NF1, a bowed tibia is one of the first signs of the disease. It most often occurs before age 2.
  
  The tibia often bows toward the front and outside of the leg; this is called an anterolateral bow. About 10% of NF1 patients develop this problem. A pediatrician should fully check a child with this type of bowing for NF1, especially if the child has no other symptoms and no NF1 diagnosis. Anterolateral bowing can occur in patients without neurofibromatosis. Still, it is linked to the disease 50% of the time. 
  
  A bowed tibia is more likely to break, or fracture. This fracture often does not heal well because the bone is deformed. The break may remain, which is known as a pseudarthrosis. Preventing this type of break is very important. Pseudarthrosis of the tibia is hard to treat and needs surgery.

(Left, left center) Pre-operative radiographs showing two different views of pseudoarthrosis in a 2-year-old girl. (Right center, right) Radiographs taken at 2-year follow-up after treatment with flexible intramedullary titanium nails.

Reproduced with permission from Vander Have K, Hensinger, R, Caird M, Johnston C, Farley F: Congenital Pseudoarthrosis of the Tibia. J Am Acad Orthop Surg 2008; 16(4): 228-236.

Neurofibromatosis Type 2 (NF2)

Neurofibromatosis Type 2 is less common. It occurs in 1 in 25,000 to 40,000 births. It is also known as bilateral acoustic neurofibromatosis (acoustic neuroma). NF2 mostly affects the central nervous system and causes tumors in the brain and spinal cord.

Hearing loss that starts in the teens or early 20s is often the first sign of NF2. People with NF2 may develop:

• Auditory nerve tumors. Most people with NF2 develop tumors on the nerves needed for hearing. These are called auditory nerves). The tumors are often benign (noncancerous). However, as they grow, they often cause hearing loss that gets worse over time.
• Other complications. People may also have ringing in one or both ears, headaches, facial pain or numbness, and trouble with balance.

Schwannomatosis

Schwannomatosis is the rarest form of neurofibromatosis and does not affect the musculoskeletal system. Mutations in the SMARCB or LZTR1 genes can cause it.

Medical History and Physical Examination

Before the physical examination, the doctor will ask about your or your child's health and current condition. The doctor will ask which symptoms are present and when they began.

During the examination, the doctor will look for skin changes, tumors, and bone abnormalities. Neurofibromatosis is often inherited. For this reason, the doctor may also examine close family members. These may include parents, siblings, and children. The doctor will check them for signs of the disease.

Tests

Imaging and laboratory tests can help diagnose neurofibromatosis and help the doctor make a treatment plan.

• X-rays. X-rays create clear pictures of bones. The doctor may order X-rays to look for skeletal deformities.
• Magnetic resonance imaging (MRI) scans. MRI scans show soft tissues. The doctor may use MRI to find soft tissue tumors when they are still small. Tumors along the nerves of the eyes and ears may be easier to treat when found early.
• Biopsy. During a biopsy, the doctor takes a tissue sample of the tumor. The sample is checked under a microscope for cancer cells.

General Guidelines for Treatment

• Children with neurofibromatosis often need regular medical exams. Doctors measure their growth and blood pressure. They also check the skin, bones, nervous system, vision, and hearing.
• Some young children have unusual spots but have not yet developed neurofibromas. Regular eye exams and screening tools may help find optic nerve gliomas early. This may allow treatment before a child starts to lose vision.
• Adults with neurofibromatosis often need yearly exams of the nervous system and hearing.
• Some people have ongoing health problems, such as pain and disability. They may need lifelong care from several medical and surgical specialists. These may include orthopaedic surgeons, neurologists, dermatologists, and radiologists.
• Some people visit multidisciplinary neurofibromatosis clinics. These clinics include many types of doctors. They provide full exams and management plans. Patients may get care at the clinic or take a plan back to their own doctor.

Treatment of Tumors

Most tumors caused by neurofibromatosis do not need treatment. However, you or your child may need treatment for tumors that are:

• Painful
• Disfiguring
• Growing fast
• Limiting the function of other body parts or pressing on them 

Some neurofibromas grow fast and may be at risk of becoming cancerous.

Treatment choices for abnormal tissue growth include:

Surgery. The doctor may cut the tumor out of the body.

Radiation. Beams of energy, called radiation, can shrink tumors and destroy cancer cells.

Chemotherapy. Chemotherapy uses drugs to kill a tumor and any cancer that has spread. It is often used first to shrink a tumor. This can make the tumor easier to remove with surgery.

Scoliosis Treatment

Scoliosis linked to neurofibromatosis may need more intensive treatment than scoliosis that is not linked to the disease.

Bracing. A doctor may suggest a brace if your child is still growing and has a curve of 15° to 25°. A brace will not make the curve straight. However, it may slow the curve or keep it from getting worse. Bracing may work better for non-dystrophic scoliosis.

Spinal fusion. The doctor may suggest surgery for severe scoliosis caused by NF1.

The operation used to treat scoliosis is a spinal fusion. It is much like a welding process. The surgeon lines up and joins the curved vertebrae. The vertebrae then heal into one solid bone. Implants keep the bones in place while the fusion heals. These implants may include screws, rods, hooks, or wires.

(Left) This X-ray shows a severe scoliosis curve in a 14-year-old boy with NF1. (Right) The same patient's spine after spinal fusion surgery.

Reproduced with permission from Feldman DS, Jordan C, Fonseca L: Orthopaedic manifestations of neurofibromatosis type 1. J Am Acad Orthop Surg 2010; 18:346-357.

Treatment for Pseudarthrosis of the Tibia

Children with NF1 and tibial bowing need special braces. The braces are made to protect the bone from fracture. If the bone breaks, surgery is often needed.

During surgery, the bone pieces are first moved into the best position. This is called reduction. Special implants then hold the pieces together.

These fractures often take a long time to heal. They are called pseudarthroses and are hard to treat. The surgeon may need to add special bone grafts to help the bone heal. Another fracture is common. This is called a refracture. The bone may not heal after several operations. If so, the surgeon, patient, and family may need to consider amputation.

(Left): An X-ray of a pseudarthrosis of the tibia in a 5-year-old child. (Right): The fracture is held together with a rod inside the bone.

Reproduced with permission from Lewis TR: Congenital pseudarthrosis of the tibia. Orthopaedic Knowledge Online Journal 2012. Accessed Apr 22, 2013.

Newer methods use implants that allow for growth and give better support. They also use extensive bone grafting. These methods can help the bone heal.