Neurocutaneous Syndromes in Children

What are neurocutaneous syndromes?

Click Image to Enlarge

Neurocutaneous syndrome is a broad term for a group of rare neurological (brain, spine, and peripheral nerve) disorders. These diseases are life-long conditions that can cause tumors to grow inside the brain, spinal cord, organs, skin, and skeletal bones. The most common disorders found in children are skin lesions.

The three most common types of neurocutaneous syndromes include the following:

• 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, it is estimated that this disease occurs in one in 6,000 persons in the US. 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 the National Institute of Neurological Disorders and Stroke (NINDS), fibromatosis Type 1 (NF1) occurs in about one in 3,000 to 4,000 births in the US. 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 US. 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). Thirty percent to fifty percent of NF cases are caused by a new mutation and 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, and only 15 percent of cases are the inherited form.

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 child may have varying degrees of symptoms associated with each condition. The following are the most common symptoms of tuberous sclerosis, neurofibromatosis, and Sturge-Weber disease. 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 in the child. Mental retardation, 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 (non-cancerous) skin tumors associated with this condition are called neurofibromas. Neurofibromas are often found growing on the nerves and in various organs of the child's body. There is a high rate of brain tumors in patients associated with NF. Less than one 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. Mental retardation is present in up to one percent of individuals with neurofibromatosis I, while other children 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 the toes.

• Sturge-Weber disease The classic symptom of this disease is a port wine stain located on the child's face, typically near or around the eye and forehead areas. A port wine stain is present from birth and is a flat area on the child 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 mental retardation. 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. Always consult your child's physician for a diagnosis.

How are neurocutaneous syndromes diagnosed?

Tuberous sclerosis, NF, and Sturge-Weber disease are congenital (present at birth). The diagnosis is made with a physical examination and diagnostic tests. During the examination, the physician obtains a complete prenatal and birth history of the child and asks if other family members are known to have any of these conditions. In older babies and children, the physician 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

Treatment of neurocutaneous syndromes

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

• Your child's age, overall health, and medical history

• The extent of the condition

• The type of condition

• Your child's tolerance for specific medications, procedures, or therapies

• Expectations for the course of the condition

• Your opinion or preference

Since neurocutaneous syndromes are life-long conditions that are not curable, the focus is on medically managing the symptoms. A child is best treated with an interdisciplinary team that may include the following healthcare providers:

• Pediatrician/family practitioner

• 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.

Lifelong considerations for a child 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 child's capabilities at home and in the community. Positive reinforcement will encourage the child to strengthen his or her self-esteem and promote independence.

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.