Neurocutaneous Syndromes

About Neurocutaneous Syndromes

Neurocutaneous syndromes are disorders that lead to growth of tumors in various parts of the body. They're caused by the abnormal development of cells in an embryo and characterized by the tumors in various parts of the body (including the nervous system) and by certain differences in the skin.

While some can be diagnosed at birth, others don't produce symptoms until later in life. Although neurocutaneous syndromes can't be cured, treatments can help manage symptoms and any health problems that occur.

Recently, important advances have been made in using DNA testing to confirm these syndromes in some people.

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 — don't 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 involving the nerves, brain, and other organs.

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

The three forms of this disorder are neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and Schwannomatosis. NF1 is the most common, accounting for about 90% of all cases.

Neurofibromatosis Type 1

NF1 (also known as von Recklinghausen disease) occurs in about 1 in 2,500 babies born worldwide. 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 pigmentary findings known as "café-au-lait" spots. These light brown or coffee-colored birthmarks may be present at birth. They typically increase in size and number during the first two years of life. A child diagnosed with NF1 must have at least six café-au-lait spots of a certain size. The spots are flat, don't itch or hurt, and don't turn into anything more serious.

Other common signs are freckling in the armpits and groin, as well as Lisch nodules, which are small noncancerous (benign) bumps on the iris, the colored part of the eye. In some cases, tumors can develop along the optic pathway and affect vision. During puberty, noncancerous tumors called neurofibromas may develop on or under the skin or along the nerves. Bone deformities also may develop.

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

Children with NF1 can also have a high prevalence of seizures, learning disabilities, attention deficit disorder (ADHD), autism, 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 25,000 births. Young adults with NF2 are typically diagnosed when they develop tumors on the vestibular nerves (the nerves leading to the ear). In contrast, young kids with NF typically have retinal abnormalities and spinal tumors.

NF2 symptoms, which appear in the teen years or early 20s, can include hearing loss, ringing in the ears, and balance problems balance. Surgery and chemotherapy can help manage these problems.

Schwannomatosis

Schwannomatosis is an even rarer type of neurofibromatosis, in which people develop multiple non-cancerous tumors involving the nerves in many areas of the body, most often the arms or legs. But unlikeNF2, they don't get vestibular nerve tumors.

In their mid-20s, people with this disorder may experience numbness, weakness, muscle atrophy, and severe pain in parts of their bodies. Treatments, such as pain medications and surgery, are available to manage these symptoms.

Tuberous Sclerosis

Tuberous sclerosis, or TS, causes non-cancerous growths called tubers  to form on organs, including the brain, eyes, kidneys, heart, lungs, bones, and skin. It occurs in about 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 varies greatly among kids, ranging from mild skin changes to learning disabilities, mental retardation, or kidney failure.

Treatment usually includes medication to control seizures, treatments to address skin problems, surgery to remove tumors, and 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 brain. What causes the mutation is unknown. So far, no genetic factors have been found. It isn't passed to children 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 sign is a facial birthmark or "port-wine stain" at birth that 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 seizures that affect the side of the body that's opposite from the port-wine stain.

About half 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 gradually worsening disease involving many major body systems. It's a recessive genetic disease, meaning that two healthy parents who carry the gene could have a child with A-T. Two parents who carry the mutated gene have a 1 in 4 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, 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 lung disease. These children often have chronic upper respiratory infections, lung infections, and pneumonia. They're also very susceptible to developing certain cancers, such as leukemia and lymphoma.

Currently, there's 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 rare genetic disorder involving the abnormal growth of blood vessels, leading to tumors. It usually affects certain areas, such as the brain and other parts of the central nervous system, the retina in the back of the eye, the adrenal glands, the kidneys, or the pancreas. Although few people have this disease, 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 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 (cancerous or non-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 depends 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 major organs. Surgery may be required to remove tumors before they create severe problems.

The outlook for VHL patients depends where the tumor is located and whether it's causing a problem to the patient. 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's easy to feel overwhelmed. Early intervention is important to help your child achieve the best quality of life possible.

It's important that your child is cared for by a team of medical experts. Treatment should 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 help, 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 about neurocutaneous syndromes.

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 is challenging, supportive therapies and treatments can help both you and your child.