Neurocutaneous Syndromes

Types of Neurocutaneous Syndromes

Common neurocutaneous syndromes that affect kids include:

• neurofibromatosis, types 1 and 2 (NF1 and NF2)
• Sturge-Weber syndrome
• tuberous sclerosis (TS)
• ataxia-telangiectasia (A-T)
• von Hippel-Lindau disease (VHL)

Symptoms vary widely from condition to condition, and they affect different kids in different ways. Often, the full effects of these diseases — even if detected at birth — do not emerge until a child grows up. The educational, social, and physical problems that the conditions cause must be managed throughout a child's life.

Neurofibromatosis

Neurofibromatosis is one of the most common neurocutaneous syndromes. It can cause tumors to grow on nerve cells, producing skin changes, bone deformities, eye problems, and other complications, particularly in the brain.

Neurofibromatosis is usually inherited, but up to half of cases occur because of spontaneous changes (mutations) within a person's genes. Once a mutation occurs, the changed (mutant) gene can then be passed on to succeeding generations. The child of a parent with neurofibromatosis has a 50% chance of inheriting the disorder.

The two different forms of this disorder are neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2). NF1 accounts for approximately 90% of all cases.

Neurofibromatosis Type 1

NF1 (also known as von Recklinghausen disease) occurs in about 1 in 4,000 babies born in the United States. To diagnose NF1, doctors take a thorough medical and family history because children with NF1 often have a parent with the disease.

The classic sign of NF1 are skin pigment findings known as "café-au-lait" spots. These light brown or coffee-colored patches may be present at birth and can look like freckles at first. They often increase in size and number during the first few years of life. A child diagnosed with NF1 will usually have at least six café-au-lait spots that are larger than freckles. The spots are flat, don't itch or hurt, and do not turn into anything more serious.

Another common sign is the presence of Lisch nodules, tiny, benign (noncancerous) tumors found on the iris of the eye. In some cases, tumors can develop along the optic nerves and affect vision. During puberty, benign tumors called neurofibromas develop on or under the skin or along the nerves of the body. Bone deformities also may develop.

NF1 treatment focuses on managing the symptoms. A child with complications involving the eye, nervous system, spine, or bones will be referred to an appropriate specialist for treatment. In cases where these neurofibromas are causing chronic pain, growing into vital body organs, or causing infections, the growths can be removed through surgery.

Children with NF1 also have a high prevalence of seizures, learning disabilities, attention deficit disorder (ADHD), and speech problems. Therapy and specialists can help manage those symptoms.

Neurofibromatosis Type 2

Neurofibromatosis type 2 is less common, occurring in about 1 in 40,000 births. Kids who have it usually develop tumors on the auditory nerves (the nerves leading to the ear), but not until adolescence or as young adults.

NF2 symptoms, which appear in the teen years or early twenties, can include hearing loss, ringing of the ears, and problems with balance. Different treatment options can help manage these problems.

Tuberous Sclerosis

Tuberous sclerosis, or TS, causes benign growths called tubers to form on different body organs, including the brain, eyes, kidneys, heart, skin, and lungs. It occurs in approximately 1 in 6,000 births, and the child of a parent with TS has a 50% chance of having it.

TS is often first recognized when a child has seizures or shows developmental delays. The severity of TS symptoms vary greatly among kids, ranging from mild skin abnormalities to cognitive delay or disability (mental retardation) or kidney failure.

Treatment usually includes medication to prevent seizures, treatments to address skin problems, surgery to remove tumors, and the management of high blood pressure caused by kidney disease.

Sturge-Weber Syndrome

Sturge-Weber syndrome is a rare condition caused by a spontaneous genetic mutation that affects the skin and the brain. What prompts the mutation is unknown and so far no genetic factors have been found. It is not passed down by parents who carry the disease. Because it frequently goes undiagnosed, it's difficult to estimate how many people are affected.

Each case of Sturge-Weber is unique and symptoms vary widely. The most visible marker is a facial birthmark or "port-wine stain" that is present at birth and usually covers at least one upper eyelid and the forehead.

Sturge-Weber syndrome can lead to neurological problems, including unusual blood vessel growths on the brain. These often cause seizures that begin before the first birthday and can worsen with age. A child also may experience convulsions on the side of the body that's opposite from the port-wine stain.

About 30% of patients also develop glaucoma (increased pressure inside the eye that impairs vision), typically in the eye that is affected by the port-wine stain. That eye also might be enlarged (a condition called buphthalmos). Some kids who have this condition also experience strokes.

Treatments, medications, and surgery can help a child cope with the health problems associated with the disease.

Children as young as 1 month old who have Sturge-Weber can undergo laser treatment to reduce or remove port-wine stains. Anticonvulsant medication may be used to control seizures, and surgery can control glaucoma and vision problems.

Ataxia Telangiectasia

Ataxia telangiectasia (A-T) is a progressive degenerative disease involving many major body systems. It is a recessive genetic disease, meaning that both parents carry the gene that could combine to cause A-T in their children but do not have the disease themselves. Two parents who carry the mutated gene have a 25% chance of having a child affected by A-T.

A-T is usually noticed in the second year of life as a child develops problems with balance and slurred speech caused by ataxia (lack of muscle control). The ataxia occurs because the cerebellum, the part of the brain that controls muscle movement, is degenerating. Eventually, the lack of muscle control becomes severe enough for the child to require a wheelchair.

Another symptom of A-T is the appearance of tiny, red, spiderlike veins in the corners of the eyes or on the ears and cheeks when exposed to sunlight. These veins, known as telangiectasias, are harmless.

About 70% of children with A-T also have immune system problems that make them more susceptible to chronic upper respiratory infections, lung infections, and pneumonia. They're also very susceptible to developing certain cancers, such as leukemia and lymphoma.

Currently, there is no cure for A-T and no way to stop its progression. But treatment can help kids manage symptoms. Physical therapy and occupational therapy may help maintain flexibility, and speech therapy can help address slurring and other speech problems. Special medications may be given to help enhance weakened immune systems.

Von Hippel-Lindau Disease

Von Hippel-Lindau disease (VHL) is a genetic disorder involving the abnormal growth of blood vessels. It usually affects certain areas, such as the brain and other parts of the central nervous system, the retina of the eye, the adrenal glands, the kidneys, or the pancreas. Its prevalence is unknown, but the child of a parent who carries the gene that causes VHL has a 50% chance of having the disorder.

Blood vessels usually grow like branches on a tree, but in kids with VHL, they form small tumors called angiomas. Doctors carefully monitor angiomas because, depending on their location, they can cause other medical problems (for example, angiomas on the retina may lead to vision loss).

Symptoms usually appear when someone is between 10 and 30 years old. VHL is diagnosed through an MRI or CT scan, a thorough physical examination, and blood tests.

Symptoms depend on the size and location of the angiomas, and can include headaches, balance problems, dizziness, weakness, vision problems, and high blood pressure. Fluid-filled cysts or tumors (benign or cancerous) may develop around the angiomas, worsening these symptoms. People with this disorder have a higher risk of developing cancer, especially kidney cancer.

VHL treatment will depend on the size and location of the angiomas. The goal is to treat the tumors while they're small and before they put pressure on any of the major organs, such as the brain or spine. Surgery may be required to remove the tumors before they create severe problems.

The prognosis for VHL patients depends on the location of the tumors and the complications they cause. Fortunately, early detection and treatment can improve treatment outcome.

Caring for Your Child

The illnesses associated with neurocutaneous syndromes can place enormous stress and emotional burdens on you and your child, and it is easy to feel overwhelmed. Early intervention is important to helping your child achieve the best quality of life possible.

The focus of treatment is to prevent or minimize complications and maximize a child's strengths. Keep these tips in mind:

• Positive reinforcement can strengthen your child's self-esteem and foster a sense of independence. Let your child find out what he or she is capable of, especially regarding daily living skills.
• Support groups can be extremely beneficial, so seek out local chapters that address your child's particular illness. They provide a supportive social environment, and are a great way to share knowledge and resources.
• Psychotherapy or other supportive treatments can boost your child's self-esteem and coping skills, so ask the treatment team for referrals. Therapy also can help other family members deal with the stress involved in caring for a child with a chronic illness or disability.
• Physical, occupational, or speech therapy can help your child improve some of the developmental delays caused by the specific illness.
• Check with your local hospital or university for seminars or informational classes about neurocutaneous syndromes. Education can help you be a valuable resource in your child's long-term treatment.

Many medical professionals might care for your child during diagnosis and treatment. These professionals can include a family practitioner, pediatrician, neurologist, neurosurgeon, orthopedic surgeon, oncologist, geneticist, and ophthalmologist. A genetic counselor also can provide information about genetic testing and the risk of passing the disease on to another child.

Remember that although each of these conditions are challenging, supportive therapies and treatments can help both you and your child.

Reviewed by: Louis E. Bartoshesky, MD, MPH
Date reviewed: May 2011