Neurofibromatosis

Overview

Tumors develop on nerve tissue as a result of a group of hereditary diseases called neurofibromatosis. Tumors can develop in various parts of the neurological system, such as the brain, spinal cord, and nerves. Neurofibromatosis comes in three different forms: schwannomatosis, neurofibromatosis 1 (NF1), and neurofibromatosis 2 (NF2). Whereas NF2 and schwannomatosis are typically detected in early adulthood, NF1 is typically diagnosed in childhood.

The tumors in these illnesses are often benign (noncancerous), but they occasionally develop into malignancy (cancerous). Symptoms are frequently minor. Nevertheless, neurofibromatosis consequences can also result in hearing loss, learning disabilities, cardiovascular issues, vision loss, and pain.

The objective of treating neurofibromatosis is to encourage proper growth and development in affected children while detecting and addressing any problems early on. In cases where the condition causes large tumors or tumors that compress a nerve, surgery can alleviate symptoms. Some patients may benefit from alternative treatments, such as stereotactic radiosurgery or pain medication. A novel medication is now available for treating tumors in children, and other advanced therapies are currently under development.

Symptoms

There are three varieties of neurofibromatosis, and each has a unique set of symptoms.

Neurofibromatosis 1 (NF1)

NF1 neurofibromatosis is typically diagnosed during childhood, with symptoms becoming apparent either at birth or shortly thereafter, and almost always by age 10. This condition is also referred to as Von Recklinghausen disease. Although the severity of symptoms may vary, they are generally mild to moderate. In up to 50% of instances, spontaneous mutation (change) can also be the cause of neurofibromatosis. The next generation may inherit the altered genes after they have already occurred.

Some warning signs and symptoms are:

• Flat, light brown spots on the skin (cafe au lait spots). These benign lesions are typical in many persons. More than six café au lait spots imply NF1. They frequently manifest at birth or in the first few years of life. Following childhood, spots no longer develop.
• Freckling in the armpits or groin area. Usually at the ages of 3 to 5, freckling begins. Freckles typically appear in groups in skin folds and are smaller than café au lait spots.
• Lisch nodules. These tiny bumps on the iris of the eye are harmless. They don’t interfere with eyesight and are difficult to spot.
• Neurofibromas (soft, pea-sized bumps on or under the skin). These benign tumors can grow inside the body, however they typically form in or beneath the skin. A growth may occasionally involve several nerves (plexiform neurofibroma). When they develop on the face, plexiform neurofibromas can be disfiguring. Age-related increases in neurofibromas are possible.
• Bone deformities. Bone abnormalities like scoliosis or a bow-legged lower leg can result from abnormal bone growth and a lack of bone mineral density.
• Optic glioma (tumor on the optic nerve). Tumor development in adults with this condition is rare, as these tumors usually begin to form by the age of 3.
• Learning disabilities. Children with NF1 frequently suffer cognitive impairment, albeit it is typically not severe. There is frequently a particular learning disability, such as difficulty with reading or math. Both speech delay and attention-deficit/hyperactivity disorder (ADHD) are common conditions.
• Macrocephaly. The head’s size is larger than it’s normal size.
• Short stature. Children diagnosed with NF1 often have below-average heights.

Neurofibromatosis 2 (NF2)

Compared to NF1, NF2 is substantially less frequent. Acoustic neuromas, which can cause hearing loss, are benign, slow-growing tumors that frequently induce the signs and symptoms of NF2. These tumors, also known as vestibular schwannomas, develop on the nerve that connects the inner ear to the brain and provides sound and balance information.

The severity of the signs and symptoms can vary, but they typically arise in late adolescence and early adulthood. Among the warning signs and symptoms are:

• Headaches
• Tinnitus (ringing in the ear)
• Gradual loss of hearing
• Unable to balance properly

Schwannomas can occasionally develop in other nerves, such as the cranial, spinal, ocular (optic), and peripheral nerves. Some benign tumors may also arise in people with NF2.

Among the warning signs and symptoms of these tumors are:

• Weakness or numbness in the upper or lower extremities
• Seizures
• Headache
• Pain
• Cataract
• Problem with eyesight
• Problem with balance
• Drooping of the face

Schwannomatosis

Symptoms of this rare type of neurofibromatosis typically begin between the ages of 25 and 30, and most individuals affected by this condition are over the age of 20. On the cranial, spinal, and peripheral nerves, tumors can form as a result of schwannomatosis; however, this seldom happens on the nerve that transmits sound and balance data from the inner ear to the brain. Those with schwannomatosis do not typically experience the same hearing loss as persons with NF2 because tumors do not typically develop on both hearing nerves.

Schwannomatosis signs and symptoms include:

• Muscle atrophy
• Chronic pain, which can affect any part of the body and is often incapacitating
• Different body areas experiencing numbness or weakness

If you or your child exhibit neurofibromatosis symptoms, visit your doctor right away. Neurofibromatosis-related tumors are frequently benign and slow-growing.

Causes

Genetic mutations that may develop spontaneously during conception or are passed down from one parent to the next are the root cause of neurofibromatosis. Depending on the kind of neurofibromatosis, specific genes may be involved:

• NF1. NF1 gene is found on chromosome 17. This gene makes the neurofibromin protein, which aids in controlling cell growth. Neurofibromin is lost as a result of the gene mutation, allowing cells to expand out of control.
• NF2. The NF2 gene, which is found on chromosome 22, generates the merlin protein, also known as schwannomin, which prevents tumor growth. The mutant gene results in the lack of merlin, which promotes uncontrolled cell proliferation.
• Schwannomatosis. Schwannomatosis has been linked to just two genes thus far. This kind of neurofibromatosis is linked to mutations in the tumor-suppressing genes SMARCB1 and LZTR1.

Risk factors

A family history of neurofibromatosis is the main risk factor for the condition. Around half of those with NF1 and NF2 received the condition from a parent who had it. Individuals with NF1 and NF2 who do not have affected relatives are more likely to have a novel gene mutation.

Both NF1 and NF2 are autosomal dominant diseases, which means that there is a 50% probability that the genetic mutation will be passed down to any offspring of an affected parent.

It is unclear how schwannomatosis is inherited. According to current research, there is a 15% chance of inheriting schwannomatosis from a parent who has the condition.