Neurofibromatosis is a genetic disorder that affects the development of nerve cells and tissues in the body, leading to the formation of tumors in different parts of the nervous system. These tumors, also known as neurofibromas, may develop in the brain, spinal cord, along the nerves, or under the skin. This neurological disorder is categorized into neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and the lesser known, Schwannomatosis. In most cases, the tumors remain noncancerous, but in some rare cases, they may become malignant. Neurofibromatosis may lead to loss of hearing, loss of vision, severe pain, and disability due to compression of nerves.
Neurofibromatosis is caused by an inherited genetic condition where in the mutated gene is passed on from one of the parents. The risk of developing this neurological disorder is about 50%, if one of the parents have the faulty gene. In some cases, a spontaneous gene mutation may also result in this neurological disorder, and about 30% of the people with neurofibromatosis belong to this category. The mutated gene can then be passed on to future generations.
Many parts of the body are affected by NF. It is a neurocutaneous syndrome. It affects the nerves, brain, spinal cord, skin and other systems of the body. It causes growth of benign tumors. In this is involves the brain and nerves. It can be either mild or severe. Some can be not affected at all whereas some can be severely disabled.
NF1 is a common genetic condition. It was first described by a German doctor Fredrich von in the year 1882.hence this condition was named after him. This condition is actually a syndrome. Often a number of features occur together. The range of severity is wide and some may be mildly affected. In majority of the cases the health of the individual is not affected. Whereas in some at certain stage of their life their condition is affected by major health problems due to NF 1. It is impossible to predict its severity and who will be affected. NF 2 is also a syndrome in which many features come together.
Some features of NF1 are:
- Flat coffee colored birth marks- these marks are harmless. It is formed due to increase in melanin in that area of the skin.
- Freckles- it happens in those areas that are not exposed to sunlight like the groin and armpit
- Tiny lumps- they develop inside the iris and only with a special lamp they are visible.
- Neruofibromas- these are small lumps that are harmless, soft and pink. In adolescence they appear but by the age of 30 there will be several. Usually they do not cause any problems.
- Plexiform neurofibromas- they occur anywhere and almost from birth they are present by the age of two they become obvious.
- Learning difficulties- almost half of people with this condition will have difficulties in learning
- Bone problems- this happens in almost 15 percent wherein the child is born with a curvature in the spine that is noticeable
- Cancer risk- the risk is slightly high. The doctor should be reported if there is any change in the symptoms of growth of neurofibroma.
Feature of NF 2
- The hearing nerves are affected.
- Other nerves may be affected that might impact speech, swallowing, facial sensations and eye movements.
- Late in adolescence the symptoms develop but until adult life they might not be obvious.
Types of NF
The three types of neurofibromatosis are NF1, NF2 and schwannomatosis.
- The most common type is NF1. This type is also known as Recklinghausen disease. In every 2500 birth, 1 may have this condition and about 1000,000 Americans are affected by this condition.
- The much rarer one is NF2. In 25,000 births one may have this condition. In this the schwannomas of the person is bilateral vestibular. These tumors are non cancerous and the nerves that carry balance and hearing information to the brain are affected.
- The third and the rarest type is schwannomatosis. In this also the tumors are non cancerous and throughout the body they affect the nerves. In this case they do not lose their hearing since tumors on the vestibular nerves are not developed. Until people reach their mid 20s this disorder is not identified and after that the symptoms of chronic pain begin.
If more than one person has NF in a family then in each person the disease may slightly differ.
The characteristic symptoms of NF1 include:
- Presence of light brown skin, called café au lait spots
- Freckles on the skin, particularly in the arm pit and groin
- Small clumps of pigments, called Lisch nodules, in the iris of the eye
- Tumors on or under the skin
- Malformation of the bones, like bowed legs and curvature of the spine (scoliosis)
- Neurological pain
- Tumors in the optic nerve
NF2 is characterized by symptoms including:
- Weakness of muscles of the face leading to facial numbness.
- Lack of coordination
- Loss of hearing or ringing noise in ears
- Atrophy of muscles
- Brain tumor
- Development of cataracts at an early age
- Lack of balance while moving
Hearing loss in NF2 is caused by the formation of tumors in vestibular nerves, or the eighth cranial nerve, which compress the acoustic nerves.
Symptoms of Shwannomatosis include:
- Tumors causing pain
- Numbness or tingling in toes
- Weakness in toes and fingers
There is no complete cure for NF1 or NF2. Different treatment options try to alleviate the symptoms of neurofibromatosis. Many symptoms, like the café au lait spots, do not require any specific treatment.
When these spots are present in the skin then in younger kids or in mild cases, NF1 can be detected early. Many people may have these spots even without NF. But if these birthmarks are present more than five and in diameter at least half inch then may indicate NF 1 and the doctor will look for other clues as well. Lisch nodules, on the iris non cancerous bumps, tumors hanging of the skin or on or under the skin, freckling in the groin or armpits are some more symptoms. Lisch nodules do not cause vision problems though they may help to diagnose NF1.
Often right before puberty starts neurofibromatosis that can be on various body parts. Other problems may also arise such as overgrowth of the bones, thinning, abnormal curved spine and sciolosis.
Until a child is older, NF2 is usually not diagnosed. Often in the 20s the first sign may appear that is hearing loss. Electrical impulses are carried from the ear to the brain by the vestibular nerves. On either side of this if tumor grows then it can result in hearing loss. Other symptoms are weakness, feeling off balance or unsteady, continuous ringing in the ears, facial pain or headache.
Even in the lining of the brain and spinal cord tumor may be involved. Retina in the back of the eye may even be affected in some.
Causes of NF
The first two types of neurofibromatosis is an inherited disorder. The chance of passing the condition to the baby is 1 in 2. Almost 50 percent of the cases of NF are inherited. In rest of them neurofibromatosis develops due to gene mutation. These changes happen spontaneously. When the sperm meets the egg eth genetic material gets changes. This happens in those win whose family NF was never present. To help check whether a person has NF and to check for mutation, blood testing will help.
Diagnosis of neurofibromatosis
If two of the following seven signs are present then the condition can be diagnosed:
- Of a certain number, size and location of café-au-lait spots
- Two or more neurofibromas appearance
- Lisch nodules present are two or more
- Skeletal defects
- Optic glioma
- A family member with NF1
- Under the arms or in the groin freckling
Patients with NF 1 can be diagnosed with the help of this list but mostly the criteria is met by children of age 8 and by the age of 20 they definitely meet the criteria. If based on these factors if the diagnosis is not certain then genetic testing can be done but the results do not predict that the person with NF1 will develop which signs. The doctor may refer you to a NF 1 specialist if the doctor suspects that the child has the condition. Medical problem associated with NF is identified with the help of other tests. This includes MRI that helps to check for bright spots in the brain which is changes in the brain, brain enlargement and tumor. Skeletal problems can be detected with the help of X- ray.
Doctors will check for any evidence of balance problem or hearing loss to diagnose NF2. Brain and spine imaging might be performed. This is to look for in the nerves of the spinal cord, ears, brain whether any tumor is present. They might order audiometry. Also they may ask questions to the family members to check for cataract and retinal problems the individual may be sent to an eye doctor. For NF2 now genetic testing is also available. Amniocentesis or chorionic villus sampling can be done for women with NF2. This is to determine whether the unborn child has neurofibromatosis.
Some of the common treatment options include:
- Surgery to remove tumors
- Chemotherapy for treating malignant tumors
- Physical therapy
- Pain management
- Surgery to treat the bone problems
- Cochlear implant after removal of tumor in the ear
Multidisciplinary team management is needed for treatment of NF. For people with NF new discoveries have come up due to the research. Currently as a part of ongoing trials these therapies are currently being offered. This is so that the affected individuals get better options.
Presence of multiple café-au-lait spots is the first visible signs of neurofibromatosis. Ask your doctor to refer any specialist if several such birthmarks are there on the child.