Neurocutaneous Syndromes

What are neurocutaneous syndromes?

Illustration of the nervous system

Neurocutaneous syndrome is a broad term for a group of neurologic (brain, spine, and peripheral nerve) disorders. These diseases are lifelong conditions that can cause tumors to grow inside the brain, spinal cord, organs, skin, and skeletal bones.

The three most common types of neurocutaneous syndromes are:

  • Tuberous sclerosis (TS)

  • Neurofibromatosis (NF): Type I, Type II, and schwannomatosis

  • Sturge-Weber disease

What causes neurocutaneous syndromes?

Tuberous sclerosis, NF, and Sturge-Weber disease are all conditions that are congenital (present at birth).

Although the true prevalence of tuberous sclerosis is not known, the National Institute of Neurological Disorders and Stroke (NINDS) estimates that this disease occurs in one in 6,000 people in the U.S. It is an autosomal dominant condition. Autosomal means that both males and females are equally affected and dominant means that only one copy of the gene is necessary to have the disorder. Many children born with TS are the first cases in a family, since the majority of TS is caused by a new gene change (mutation), and is not inherited. However, parents of a child with TS may have very subtle symptoms of the disorder, and should be carefully examined. Even if no symptoms are present, the parents are considered at a slightly increased risk to have another child with TS, greater than that of the general population.

According to NINDS, fibromatosis Type 1 (NF1) occurs in about one in 3,000 to 4,000 births in the U.S. NF1 is an autosomal dominant condition caused by a gene on chromosome 17, which is inherited from a parent with the disease (in half of the cases). Neurofibromatosis Type 2 (NF2) occurs less frequently, affecting about one in 25,000 births in the U.S. The gene which causes NF2 is found on chromosome 22.

A parent with NF has a 50/50 chance of having a child with the disease. 

NF may also be the result of a new gene change (mutation). Half of NF cases are caused by a new mutation and are not inherited. Males and females are equally affected, regardless of how the disease occurs. Schwannomatosis is a recently-recognized form of NF that is genetically distinct from NF1 and NF2. It occurs rarely, typically first appearing in people older than age 30, and only 15 percent of cases are the inherited form. It affects roughly one in 40.000 live births.

The cause of Sturge-Weber disease is unknown and is considered to be sporadic (occurs by chance). Sometimes, other family members will have hemangiomas (a benign growth that consists of blood vessels) to a lesser degree than the person with Sturge-Weber disease.

What are the symptoms of neurocutaneous syndromes?

The following are the most common symptoms of tuberous sclerosis, neurofibromatosis, and Sturge-Weber disease. However, each individual may experience symptoms differently. Symptoms may include:

  • Tuberous sclerosis. Growths, called tubers, are often found growing inside of the brain and retinal area of the eye. Tuberous sclerosis affects many organs in the body including the brain, spinal cord, lungs, heart, kidneys, skin, and skeletal bones. Intellectual disability, developmental delays, seizures, and learning disabilities are also associated with this disease.

  • Neurofibromatosis (NF). There are three distinct types of NF, classified as NF I, NF II, and schwannomatosis:

    • Neurofibromatosis I. This is the more common of the two disorders. It is also called Von Recklinghausen's disease. The classic symptom of NF I is light brown patches of pigment on the skin, called cafe-au-lait spots. Benign (noncancerous) skin tumors associated with this condition are called neurofibromas. Neurofibromas are often found growing on the nerves and in various organs of the person's body. There is a high rate of brain tumors in patients associated with NF. Less than 1 percent of individuals with NF will have malignant (cancerous) changes in the neurofibromas. Lisch nodules, which are small tumors on the iris (colored part of the eye), may appear around adolescence, but usually do not cause problems. Hearing loss, headaches, seizures, scoliosis, and facial pain or numbness may also be present. Intellectual disability is present in up to 1 percent of individuals with neurofibromatosis I, while other people affected may have learning problems and hyperactivity.

    • Neurofibromatosis II. According to the NINDS, this type of neurofibromatosis affects approximately one in 25,000 people, and symptoms are usually noticed between 18 and 22 years of age. It is known as bilateral acoustic neurofibromatosis and is less common. This disease is characterized by tumors on the eighth cranial nerve, which can lead to hearing loss, headaches, problems with facial movements, problems with balance, and difficulty walking. Hearing loss may be noted as early as the teenage years. Other clinical signs of NF II may include seizures, neurofibromas (skin nodules), and cafe-au-lait spots, although these are not nearly as common as in NF I.

    • Schwannomatosis. The primary feature which distinguishes schwannomatosis from NF1 and NF2 is the growth of multiple schwannomas throughout the body except the vestibular nerve is not involved. Extremely intense pain is the main symptom, which occurs when a schwannoma becomes larger or presses on a nerve or nearby tissue. Other symptoms that may be experienced include numbness, tingling, or weakness in the fingers and toes.

  • Sturge-Weber disease. The classic symptom of this disease is a port-wine stain located on the face, typically near or around the eye and forehead areas. A port-wine stain is present from birth and is a flat area that varies in color from red to dark purple. The birthmark is caused by the formation of too many tiny blood vessels under the skin. There may also be associated brain abnormalities on the same side of the brain as the face lesion. Neurological changes that occur with this condition may include seizures, muscle weakness, changes in vision, and intellectual disability. Glaucoma, a condition that causes increased pressure in the eye, may also be present at birth. Unlike tuberous sclerosis and NF, Sturge-Weber disease does not affect the other organs of the body.

The symptoms of neurocutaneous syndromes may resemble other conditions or medical problems. Always consult your doctor for a diagnosis.

How are neurocutaneous syndromes diagnosed?

Tuberous sclerosis, NF, and Sturge-Weber disease are congenital, or present at birth. The diagnosis is made with a physical examination and diagnostic tests. During the examination, the doctor obtains a complete medical history and asks if other family members are known to have any of these conditions. In babies and children, the doctor will also ask about developmental milestones, since these disorders can be associated with other neurological problems and may require further medical follow-up.

Diagnostic tests may include:

  • Blood tests

  • Genetic testing. Diagnostic tests that evaluate for conditions that have a tendency to run in families.

  • X-ray. A diagnostic test that uses invisible electromagnetic energy beams to produce images of internal tissues, bones, and organs onto film.

  • Magnetic resonance imaging (MRI). A diagnostic procedure that uses a combination of large magnets, radiofrequencies, and a computer to produce detailed images of organs and structures within the body.

  • Computed tomography scan (also called a CT or CAT scan). A diagnostic imaging procedure that uses a combination of X-rays and computer technology to produce horizontal, or axial, images (often called slices) of the body. A CT scan shows detailed images of any part of the body, including the bones, muscles, fat, and organs. CT scans are more detailed than general X-rays.

  • Electroencephalogram (EEG). A procedure that records the brain's continuous, electrical activity by means of electrodes attached to the scalp.

  • Eye examination

  • Tissue sample of the tumor or skin lesion

How are neurocutaneous syndromes treated?

Specific treatment for neurocutaneous syndromes will be determined by your doctor based on:

  • Your age, overall health, and medical history

  • Extent of the condition

  • Type of condition

  • Your tolerance for specific medications, procedures, or therapies

  • Expectations for the course of the condition

  • Your opinion or preference

Since neurocutaneous syndromes are lifelong conditions that are not curable, the focus is on medically managing the symptoms. A person is best treated with an interdisciplinary team that may include the following health care providers:

  • Pediatrician/family practitioner/internist

  • Neurologist. A doctor who specializes in conditions of the brain, nerves, and spinal cord.

  • Neurosurgeon. A surgeon who specializes in operating on the brain and spinal cord.

  • Orthopedic surgeon. A surgeon who specializes in conditions of the muscles, tendons, ligaments, and bone.

  • Ophthalmologist. A doctor who specializes in conditions of the eye.

  • Nurse

  • Rehabilitation team (physical, occupational, speech therapy, audiology)

Surgery may be needed to remove tumors that may be cancerous, as well as for cosmetic reasons.

What are the lifelong considerations for a person with neurocutaneous syndromes?

Since tuberous sclerosis, NF, and Sturge-Weber disease are lifelong conditions that are not correctable, management includes focusing on preventing or minimizing deformities and maximizing the person's capabilities at home and in the community. Positive reinforcement will encourage the people to strengthen his or her self-esteem and promote independence.

In children, the full extent of the disease is usually not completely understood immediately after birth, but may be revealed as the child grows and develops.

Genetic counseling may be recommended by the doctor to provide information on the recurrence risks for these disorders and any available testing.