Neurocutaneous Syndrome

Neurocutaneous syndromes are diagnosed as one of the following four conditions:

• Tuberous sclerosis (TS): Tuberous sclerosis complex, also known as tuberous sclerosis, is a rare genetic disease that causes non-cancerous (benign) tumors to grow in the brain and several areas of the body, including the spinal cord, nerves, eyes, lung, heart, kidneys and skin. The name tuberous sclerosis comes from the characteristic tuber or potato-like nodules in the brain, which are affected by calcium with age and become hard or sclerotic. TS is a lifelong condition.
• Neurofibromatosis (NF1 and NF2): Tumors, or neurofibromas, grow along the body’s nerves or on or underneath the skin. Scientists have classified NF into two distinct types: neurofibromatosis type 1 (NF1) and NF2. NF1, formerly known as von Recklinghausen’s NF, is the more common of the types. It occurs in approximately 1 in 4,000 births. NF2, also referred to as bilateral acoustic NF, central NF or vestibular NF, occurs less frequently: 1 in 40,000 births. Occurrences of NF1 and NF2 are present among all racial groups and affect both sexes equally. The tumors arise from changes in the nerve cells and skin cells. Tumors also may press on the body’s vital areas as their size increases. NF may lead to developmental abnormalities and/or increased chances of having learning disabilities. Other forms of NF, where the symptoms are not consistent with that of NF1 or NF2, have been observed. A rare form of NF is schwannomatosis. However, the genetic cause of this form of NF has not been found.
• Schwannomatosis (SWNTS1 and SWNTS2): Schwannomatosis is a rare form of neurofibromatosis that is primarily characterized by multiple schwannomas (benign tumors of the nervous system) in the absence of bilateral (affecting both sides) vestibular schwannomas. Signs and symptoms of the condition vary based on the size, location and number of schwannomas but may include pain, numbness, tingling and/or weakness in the fingers and toes. Inherited forms of the disorder account for only 15 percent of all cases. In some of these families, Schwannomatosis is caused by changes in the SMARCB1 or LZTR1 genes; in other cases, the exact underlying cause is unknown. When inherited, the condition is passed down in an autosomal dominant manner with highly variable expressivity and reduced penetrance.
• Sturge-Weber Syndrome (SWS): This neurological condition causes an overgrowth of blood vessels that form growths called angiomas, which can lead to “port-wine” type facial birthmarks. These growths can also form on the brain and can cause seizures.

Neurocutaneous syndromes are genetic (caused by gene mutations) and are congenital, and therefore diagnosed at birth. Both boys and girls are equally at risk for these syndromes.

Tuberous sclerosis (TS) is caused by genetic mutations on either the TSC1 or TSC2 gene. Only one of the genes needs to be affected for TSC to be present. A mutation of either one of these genes leads to abnormal development and exponential growth of cells within the body.

The TSC1 gene produces a protein called hamartin. The TSC2 gene produces the protein tuberin. Scientists believe these proteins act as growth suppressors by silencing or interfering with the activation of a protein called mTOR. Loss of regulation of mTOR occurs in cells lacking either hamartin or tuberin, and this leads to abnormal cell changes and development, and to the generation of enlarged cells, as are seen in TS brain lesions.

Although some cases of TS are inherited from a parent, most cases are sporadic (developing on their own) due to new, spontaneous mutations in TSC1 or TSC2—meaning neither parent has the disorder or the genetic mutation(s).

In rare instances, people may acquire TS through a process called gonadal mosaicism. These individuals have parents with no apparent mutations in the TSC1 or TSC2 gene. These parents can have a child with TS because a portion of one of the parent’s reproductive cells (sperm or eggs) can contain the genetic mutation without the other cells of the body being involved.

Schwannomatosis (SWNTS) is a rare, genetic subform of NF. SWNTS1 (also called congenital cutaneous neurilemmomatosis) is a genetic mutation present at birth. SWNTS2 varies in that it is diagnosed in adulthood, and presents as schwannomas to develop throughout the body.

Sturge-Weber syndrome is a rare, neurological disorder present at birth and characterized by a port-wine-stain birthmark on the forehead and upper eyelid on one side of the face. The birthmark can vary in color from light pink to deep purple and is caused by an overabundance of capillaries (small blood vessels) around the trigeminal nerve just beneath the surface of the face.

Sturge-Weber syndrome is also accompanied by abnormal blood vessels on the brain’s surface and the loss of tissue (atrophy) with deposits of calcium (calcification) in the cerebral cortex of the brain on the same side as the birthmark. Sturge-Weber syndrome rarely affects other body organs.

Researchers believe that Sturge-Weber disease, a noncancerous growth made of blood vessels, occurs by chance. Children with this diagnosis sometimes have mutations in the gene GNAQ.

Neurofibromatosis occurs in both biological sexes and in all races and ethnic groups. Why tumors develop in these conditions isn’t completely known, but it appears to be caused in part by mutations in genes that play key roles in suppressing growth in nervous system cells. These mutations keep the genes—identified as NF1, NF2, SMARCB1 and LZTR1—from making normal proteins that control the ability of the cells to function properly. Without the normal function of these proteins, cell growth increases, leading to the formation of tumors.

Schwannomatosis is a form of neurofibromatosis and occurs in both biological sexes and in all races and ethnic groups. Why this condition occurs isn’t completely known, but it appears to be caused in part by mutations in genes that play key roles in suppressing growth in nervous system cells. These mutations keep the genes—identified as NF1, NF2, SMARCB1 and LZTR1—from making normal proteins that control the ability of the cells to function properly. Without the normal function of these proteins, cell growth increases, leading to the formation of tumors.

Neurocutaneous syndromes are genetic (caused by gene mutations) and are congenital, and therefore diagnosed at birth. Both boys and girls are equally at risk for this disease.

It may be impossible to distinguish someone with NF2 from schwannomatosis based on clinical features alone. Genetic testing may be needed to correctly diagnose individuals with features of these conditions who lack a known family history or bilateral vestibular schwannomas (those that occur on both sides of the body). Genetic testing can be useful in some situations, such as for prenatal testing or when the clinical diagnosis is inconclusive.

Detailed imaging of the brain and spinal cord by MRI is necessary, and additional imaging based on symptoms may reveal schwannomas on peripheral nerves.

It may be impossible to distinguish someone with neurofibromatosis 2 (NF2) from schwannomatosis (SWN) based on clinical features alone. Genetic testing may be needed to correctly diagnose individuals with features of these conditions who lack a known family history or bilateral vestibular schwannomas (those that occur on both sides of the body). Genetic testing can be useful in some situations, such as for prenatal testing or when the clinical diagnosis is inconclusive.

Detailed imaging of the brain and spinal cord by MRI is necessary, and additional imaging based on symptoms may reveal schwannomas on peripheral nerves.

Infants with a high-risk distribution of port-wine stains are commonly screened for Sturge-Weber syndrome using brain magnetic resonance imaging. There is no consensus about which port-wine stain phenotypes to screen, optimal timing, screening sensitivity or whether presymptomatic diagnosis improves neurodevelopmental outcomes.

Symptoms of tuberous sclerosis (TS) include:

• Seizures: Most people with TS are affected by seizures at some time in their life. While some kinds of seizures caused by TS result in obvious convulsive movements, others alter awareness, behavior or postural tone without convulsions.
• Cognitive difficulties: Developmental delay occurs in about one-half to two-thirds of people with TS. Delays range from mild learning disabilities to severe impairment of cognitive abilities.
• Behavior problems: Aggressive behavior, sudden rage, attention deficit hyperactivity disorder, acting out, obsessive-compulsive disorder and repetitive, destructive or self-harming behavior occur in children with TS and can be difficult to manage.
• Autism spectrum disorder: There is a strong relationship between autism spectrum disorder and TS. Many children with TS develop autism spectrum disorder.

Skin abnormalities vary widely in individuals with TS. Some cases may cause disfigurement and may need to be treated. The most common skin abnormalities include:

• Hypomelanic macules ("ash leaf spots"), which are white or lighter patches of skin that may appear anywhere on the body and are caused by a lack of skin pigment or melanin—the substance that gives skin its color.
• Facial angiofibromas (also known as adenoma sebaceum) are reddish spots or bumps that appear on the face (sometimes resembling acne) and consist of blood vessels and fibrous tissue.
• Forehead plaques are raised, discolored areas on the forehead which are common and unique to TS and may help doctors diagnose the disorder.
• Shagreen patches are areas of thick leathery, pebbly skin, usually found on the lower back or nape of the neck.
• Ungual or subungual fibromas are small fleshy tumors that grow around and under the toenails or fingernails and may need to be surgically removed if they enlarge or cause bleeding. These usually appear later in life, ages 20–50.
• Other skin features that are not unique to individuals with TSC include molluscum fibrosum or skin tags, which typically occur across the back of the neck and shoulders; café-au-lait spots or flat brown marks; and poliosis, a tuft or patch of white hair that may appear on the scalp or eyelids.

Kidney problems are also a symptom of TS. Cysts and angiomyolipomas (benign growths of fatty tissue and muscle cells) occur in an estimated 70 to 80 percent of individuals with TS. They usually occur between ages 15 and 30.

• Cysts are usually small, appear in limited numbers, and most often cause no serious problems. A very small percentage of individuals with TS develop large numbers of cysts during childhood, which may lead to bleeding, anemia and kidney failure.
• Angiomyolipomas are the most common kidney lesions in TS and can be found in people without TS. Angiomyolipomas caused by TS are usually found in both kidneys and in most cases do not produce symptoms. However, they can sometimes grow so large that they cause pain or kidney failure. Bleeding from angiomyolipomas may also occur, causing both pain and weakness and, in some instances, severe blood loss resulting in profound anemia and a life-threatening drop in blood pressure, warranting urgent medical attention.
• Other rare kidney problems include renal cell carcinoma, developing from an angiomyolipoma, and oncocytomas, benign tumors unique to individuals with TS.

Lung lesions are present in about one-third of adult women with TS and are much less commonly seen in men. Lung lesions include lymphangioleiomyomatosis (LAM) and multinodular multifocal pneumocyte hyperplasia (MMPH).

• LAM is a tumor-like disorder in which cells increase in the lungs, and there is lung destruction with cyst formation. A range of symptoms can occur with LAM, with many TS individuals having no symptoms, while others suffer with breathlessness, which can progress and be severe.
• MMPH is a more benign tumor that occurs in men and women equally.

Neurofibromatosis is not a single medical disorder. It refers to three different conditions involving the development of tumors that may affect the brain, the spinal cord and the nerves that send signals between the brain and spinal cord and all other parts of the body. Most tumors are non-cancerous (benign), although some may become cancerous (malignant).

The conditions are:

1. Neurofibromatosis type 1 (NF1), also known as von Recklinghausen disease
2. Neurofibromatosis type 2 (NF2)
3. Schwannomatosis (SWN)

Neurofibromatosis 1 (NF1) is the most common of the three conditions. Although many people with NF1 inherit the gene that causes the condition, between 30 and 50 percent of cases arise from a spontaneous genetic mutation in the NF1 gene. Once this mutation has occurred, the abnormal gene can be inherited. Each child of an affected parent has a 50 percent chance of inheriting the gene mutation.

Children and adults with NF1 can have a variety of symptoms and medical problems that can change across a lifespan. Most people with NF1 have an average life expectancy. Because many of the other clinical features of NF1 develop as an individual ages, getting the correct diagnosis may take several years.

Signs and symptoms of NF1 include:

• Children with NF1 are usually shorter than average and have larger heads.
• Cardiovascular complications, such as congenital heart defects, high blood pressure (hypertension) and constricted, blocked or damaged blood vessels.
• Poor visuospatial skills and poor performance on academic achievement tests, including those that measure reading and math skills.
• Behavioral challenges, such as attention-deficit/hyperactivity disorder (ADHD) and social skills, are commonly seen in children with NF1.
• Although common in all people, headaches, pain and seizures happen more often in people with NF1.
• Tumors that may become cancerous. An estimated 10 percent of plexiform neurofibromas may become malignant, requiring aggressive treatment. Cutaneous neurofibromas are not known to become malignant.
• Malignant glioma is a type of tumor that can occur (although rarely) in adults with NF1.
• Adult young women with NF1 are at a higher risk for breast cancer arising before the age of 50 years than women in the general public.
• There is an increased risk of gastrointestinal stromal tumors (GIST) and neuroendocrine tumors, like pheochromocytoma. There also is an increased incidence of benign nerve tumors called glomus tumors.
• Scoliosis, or curvature of the spine, can be more common and aggressive in people with NF1.

Neurofibromatosis 2 (NF2) is less common than NF1. Approximately 50 percent of affected people inherit the gene (familial); in others, however, the condition is caused by a spontaneous genetic mutation in the NF2 gene. Each child of an affected parent has a 50 percent chance of inheriting the abnormal NF2 gene.

Signs and symptoms of NF2 result from the development of:

• Benign, slow-growing tumors affecting the cranial, spinal and peripheral nerves, as well as the covering of the brain and spinal cord (called the meninges).
  • Schwannomas are tumors made up of Schwann cells, or the cells that produce the myelin that covers and protects peripheral nerves throughout the body. They often occur on the eighth cranial nerve, which has two branches: The acoustic branch carries the signals for hearing to the brain and the vestibular branch carries signals for sense of position and balance. Vestibular schwannomas (also known as acoustic neuromas) are the most recognized form of schwannoma in people with NF2, but schwannomas can involve any of the cranial or peripheral nerves in someone with NF2. Schwannomas also can occur in the skin and appear as bumps under the skin or on the skin surface. Most tumors are benign, although, very rarely, they may become cancerous. Schwannomas may or may not progress over time and many never require treatment.
  • Meningioma is the second most common tumor type in people who have NF2. Meningiomas form in the tissue covering that surrounds the brain and spinal cord. People with NF2 have both a higher rate of meningiomas than the general population and can develop multiple meningiomas within the skull and along the spinal column.
  • Ependymoma tumors occur more frequently in people with NF2 than in the general population. Ependymomas arise within the spinal cord (as opposed to on the surface) and are benign. In many individuals, these tumors produce or show no symptoms.
• People with NF2 may develop vision problems like cataracts at an earlier age or have changes in the retina that can affect vision.
• Individuals with NF2 may develop peripheral neuropathy, or problems with nerve function, usually numbness and weakness on both sides of the body (with or without muscle loss) in the arms and legs.

While teenagers and adults often are first seen for hearing and balance problems, young children with NF2 more commonly seek initial medical attention due to vision problems and meningiomas.

Signs of NF2 may be present in childhood but can be overlooked, especially in children who do not have a family history of NF2. Children are often first seen by a doctor because of schwannomas in the skin, vision loss from retinal abnormalities or tumors, seizures or weakness related to spinal cord compression. More commonly, symptoms of NF2 are first noticed in the second decade of life.

The most common first symptom is hearing loss or ringing in the ears (tinnitus) related to vestibular schwannomas. Less often, the first visit to a doctor will be because of disturbances in balance, visual impairment, focal weakness in an arm or leg, seizures, or skin tumors.

Schwannomatosis (SWN) is the rarest form of the three conditions and is genetically and clinically distinct from NF1 and NF2. In many cases, mutation of the SMARCB or LZTR1 genes is associated with the disease; however, the genetic cause of SWN in some people is unknown.

Signs and symptoms of SWN significantly overlap with those of NF2 since they result from the development of slow-growing schwannomas of the cranial, spinal and peripheral nerves and in some cases meningiomas of the brain and spinal cord. About one-third of individuals with schwannomatosis have tumors limited to a single part of the body, such as an arm, leg or a segment of the spine. Some people develop many tumors, while others develop only a few. Schwannomas or meningiomas in the setting of schwannomatosis sometimes show no symptoms.

Other symptoms of SWN a doctor may look for are:

• Chronic pain anywhere on the body. Chronic pain affects many people with SWN; this pain may or may not be associated with a specific schwannoma.
• Numbness, tingling or weakness in the fingers and toes and/or loss of muscle function.

Sturge-Weber syndrome is also accompanied by abnormal blood vessels on the brain’s surface and the loss of tissue (atrophy) with deposits of calcium (calcification) in the cerebral cortex of the brain on the same side as the birthmark. Sturge-Weber syndrome rarely affects other body organs.

Neurological symptoms may include:

• Seizures that begin in infancy and may worsen with age. Convulsions usually happen on the side of the body opposite the birthmark and vary in severity.
• Intermittent or permanent muscle weakness.
• Developmental delays and cognitive impairment.
• Glaucoma (increased pressure within the eye) at birth or later. The increased pressure within the eye can cause the eyeball to enlarge and bulge out of its socket (buphthalmos).
• Migraines.

Diagnosing tuberous sclerosis (TS) is based upon clinical criteria that include identifying signs and symptoms, looking at family history, and using diagnostic imaging such as CT scans or MRI (particularly in the brain) and ultrasound of the heart, liver and kidneys. Seizures and delayed development may be the first clues of having TS. An examination of the skin, fingernails, toenails, teeth, gums and eyes will also help doctors diagnose the disorder.

In infants, TS may be suspected if the child has cardiac rhabdomyomas at birth or seizures (especially the kind called infantile spasms) in the first six months of life. With a careful examination of the skin and brain, it may be possible to diagnose TS in a very young infant. However, many children are not diagnosed until later in life when their seizures begin and other symptoms appear.

It may be impossible to distinguish someone with NF2 from schwannomatosis based on clinical features alone. Genetic testing may be needed to correctly diagnose individuals with features of these conditions who lack a known family history or bilateral vestibular schwannomas (those that occur on both sides of the body). Genetic testing can be useful in some situations, such as for prenatal testing or when the clinical diagnosis is inconclusive.

Detailed imaging of the brain and spinal cord by MRI is necessary, and additional imaging based on symptoms may reveal schwannomas on peripheral nerves.

To diagnose NF1, a doctor looks for some of the following:

• Six or more flat, light brown spots on the skin (“café-au-lait” spots), which are the most common feature of NF1. These multiple birthmarks measure more than five millimeters in diameter in children or more than 15 millimeters across in adolescents and adults. They are seen at birth or develop during the first few years of life. Café-au-lait spots are not dangerous but indicate the possible presence of an NF1 gene change in the person. These skin marks also occur in other conditions, such as Legius syndrome, a genetic condition that affects how cells in the body communicate.
• Two or more soft, pea-sized bumps involving the skin (cutaneous neurofibromas), or one larger neurofibroma that involves multiple nerves (plexiform neurofibroma). Neurofibromas are tumors that originate from nerve cells. Plexiform neurofibromas are nerve-associated tumors involving nerves outside of the brain and spinal cord. They can be present at birth or may not become noticeable for many years. Although some cutaneous neurofibromas arise in childhood, most appear during or after the teenage years.
• Freckling in the armpits or the groin. This usually appears by three to five years of age. Freckles are similar in appearance to café-au-lait spots but are smaller in size. Freckling can occur in other conditions, but not with the other symptoms and concerns of NF1.
• Two or more growths on the iris of the eye (known as Lisch nodules or iris hamartomas). These nodules are harmless, not typically present until adolescence, do not affect vision, and do not require monitoring or treatment.
• A tumor of the optic pathway (optic pathway glioma). These tumors typically first appear by age six, rarely in late childhood and adolescence, and almost never in adults. Although they can affect vision, most do not become symptomatic.
• Bone deformities. Abnormal development of the eye socket (sphenoid) or the tibia (one of the long bones of the shin).
• A parent, sibling or child with NF1.

To diagnose NF2, a doctor will look for the following:

• Vestibular schwannomas
• A parent, sibling or child with NF2

They will also look for a unilateral vestibular schwannoma (on one side of the body) before age 30 or any of the following:

• Ependymoma
• Meningioma
• Schwannoma of non-vestibular nerves
• Juvenile cataract or retinal abnormalities

It may be impossible to distinguish someone with NF2 from schwannomatosis based on clinical features alone. Genetic testing may be needed to correctly diagnose individuals with features of these conditions who lack a known family history or bilateral vestibular schwannomas (those that occur on both sides of the body). Genetic testing can be useful in some situations, such as for prenatal testing or when the clinical diagnosis is inconclusive.

Detailed imaging of the brain and spinal cord by MRI is necessary, and additional imaging based on symptoms may reveal schwannomas on peripheral nerves.

Infants with a high-risk distribution of port-wine stains are commonly screened for Sturge-Weber syndrome using brain magnetic resonance imaging. There is no consensus about which port-wine stain phenotypes to screen, optimal timing, screening sensitivity or whether presymptomatic diagnosis improves neurodevelopmental outcomes.

NF1 cannot be cured, but treatments can help manage signs and symptoms. Many people with NF1 will not require any prolonged treatment for any manifestation (disease signs or development) during their lives. People with NF1 should be evaluated periodically by an NF1 specialist, even if they are not experiencing symptoms, to evaluate for signs or symptoms that may indicate a need for treatment and to provide reassurance that treatment is not needed when appropriate.

The U.S. Food and Drug Administration (FDA) approved selumetinib (Koselugo) as a treatment for children ages two years and older with NF1. The drug helps to stop tumor cells from growing.

Surgery may be used to remove tumors that develop symptoms or are of concern for cancer, as well as for tumors that cause significant discomfort. Several surgical options exist for many of the manifestations of NF1, but there is no general agreement among doctors about when surgery should be performed, or which surgical option is best. Some bone malformations, such as scoliosis, can be corrected surgically or by stabilizing the spine with a brace. Some malformations that affect blood vessels can be successfully addressed with surgery or non-surgical procedures.

Chemotherapy may be used to treat optic pathways or other brain gliomas. The drug selumetinib (Koselugo®) has been approved by the FDA to treat children older than two years of age who have symptoms but inoperable plexiform neurofibromas. Chemotherapy regimens are a core part of treating cancers that may arise in the setting of NF1, including malignant peripheral nerve sheath tumor (MPNST) and breast cancer.

Treatments for other conditions associated with NF1 are aimed at controlling or relieving symptoms. Headache and seizures are treated with medications. Because children with NF1 have a higher-than-average risk for a variety of learning disabilities, ADHD, motor delays and autism, they should be evaluated by a care team knowledgeable in NF1, and may be advised to have formal neuropsychological assessments to assist in creating individualized educational plans for school.

NF2 is best managed at a specialty clinic with an initial screening and annual follow-up evaluations (more frequent if the disease is severe). Improved diagnostic technologies, such as magnetic resonance imaging (MRI), can reveal tumors of the vestibular nerve as small as a few millimeters in diameter. Vestibular schwannomas grow slowly, but they can grow large enough to engulf one of the eight cranial nerves as well as cause brain stem compression and damage to surrounding cranial nerves.

Surgical options depend on tumor size and the extent of hearing loss. There is no general agreement among doctors about when surgery should be performed or which surgical option is best. Individuals considering surgery should carefully weigh the risks and benefits of all options to determine which treatment is right for them.

There is no currently accepted medical treatment or drug for schwannomatosis. Surgery may help some people with growing tumors or symptoms that are directly referred to individual schwannomas. However, the potential risk of nerve damage must be weighed carefully against potential benefits of surgery.

There is no currently accepted medical treatment or drug for schwannomatosis. Surgery may help some people with growing tumors or symptoms that are directly referred to individual schwannomas. However, the potential risk of nerve damage must be weighed carefully against potential benefits of surgery.

Treatment is symptomatic. Laser treatment may be used to lighten or remove the birthmark. Anticonvulsant medications may be used to control seizures. Physical therapy may help with muscle weakness and educational therapy may help those with impaired cognition or developmental delays. Doctors recommend yearly monitoring for glaucoma.

Although it is possible for the birthmark and atrophy in the cerebral cortex to be present without symptoms, most infants will develop convulsive seizures during their first year of life. There is a greater likelihood of intellectual impairment when seizures start before the age of two and are resistant to treatment.

Currently there is no cure for tuberous sclerosis, but treatment is available for a number of symptoms. Treatment is symptomatic and supportive, such as early developmental interventions to reduce the risk of developmental delays. Interventions may include physical, occupational, speech and behavioral therapy. Since TS is unique to each person, an individualized treatment plan will provide the best possible disorder management.

Antiepileptic drugs may be used to control seizures. Vigabatrin is a particularly useful medication in TS and has been approved by the U.S. Food and Drug Administration (FDA) for treatment of infantile spasms in TS, although it has significant side effects. The FDA has approved the drug everolimus (Afinitor®) to treat certain brain and kidney tumors, in addition to intractable seizures (seizures not controlled well by medicine). Special medications may be prescribed for behavioral problems. Surgery may be needed to remove tumors from affected organs if they are not properly functioning. If lung lesions are severe enough, they can be treated with supplemental oxygen therapy or lung transplantation.

Basic laboratory studies have revealed insight into the function of the TS genes and have led to use of rapamycin (mTOR) inhibitors and related drugs for treating some of the manifestations of TS.

Surgery may be used to remove tumors that develop symptoms or are of concern for cancer, as well as for tumors that cause significant discomfort. Several surgical options exist for many of the manifestations of NF1, but there is no general agreement among doctors about when surgery should be performed, or which surgical option is best. Some bone malformations, such as scoliosis, can be corrected surgically or by stabilizing the spine with a brace. Some malformations that affect blood vessels can be successfully addressed with surgery or non-surgical procedures.

Chemotherapy may be used to treat optic pathways or other brain gliomas. The drug selumetinib (Koselugo®) has been approved by the FDA to treat children older than two years of age who have symptoms but inoperable plexiform neurofibromas. Chemotherapy regimens are a core part of treating cancers that may arise in the setting of NF1, including malignant peripheral nerve sheath tumor (MPNST) and breast cancer.

Treatments for other conditions associated with NF1 are aimed at controlling or relieving symptoms. Headache and seizures are treated with medications. Because children with NF1 have a higher-than-average risk for a variety of learning disabilities, ADHD, motor delays and autism, they should be evaluated by a care team knowledgeable in NF1, and they may be advised to have formal neuropsychological assessments to assist in creating individualized educational plans for school.

NF2 is best managed at a specialty clinic with an initial screening and annual follow-up evaluations (more frequent if the disease is severe). Improved diagnostic technologies, such as magnetic resonance imaging (MRI), can reveal tumors of the vestibular nerve as small as a few millimeters in diameter. Vestibular schwannomas grow slowly, but they can grow large enough to engulf one of the eight cranial nerves as well as cause brain stem compression and damage to surrounding cranial nerves.

Surgical options depend on tumor size and the extent of hearing loss. There is no general agreement among doctors about when surgery should be performed or which surgical option is best. Individuals considering surgery should carefully weigh the risks and benefits of all options to determine which treatment is right for them.

NF2 is best managed at a specialty clinic with an initial screening and annual follow-up evaluations (more frequent if the disease is severe). Improved diagnostic technologies, such as magnetic resonance imaging (MRI), can reveal tumors of the vestibular nerve as small as a few millimeters in diameter. Vestibular schwannomas grow slowly, but they can grow large enough to engulf one of the eight cranial nerves as well as cause brain stem compression and damage to surrounding cranial nerves.

Surgical options depend on tumor size and the extent of hearing loss. There is no general agreement among doctors about when surgery should be performed or which surgical option is best. Individuals considering surgery should carefully weigh the risks and benefits of all options to determine which treatment is right for them.

There is no currently accepted medical treatment or drug for schwannomatosis. Surgery may help some people with growing tumors or symptoms that are directly referred to individual schwannomas. However, the potential risk of nerve damage must be weighed carefully against potential benefits of surgery.

Parents can assist their child with SWD as they grow by learning more about the diagnosis, continuing to attend regular checkups, and talking with their physicians about managing symptoms, if any.

Consider participating in a clinical trial so clinicians and scientists can learn more about neurocutaneous syndromes. Clinical research uses human volunteers to help researchers learn more about a disorder and perhaps find better ways to safely detect, treat or prevent disease.

All types of volunteers are needed—those who are healthy or may have an illness or disease—of all different ages, sexes, races and ethnicities to ensure that study results apply to as many people as possible, and that treatments will be safe and effective for everyone who will use them.

For information about participating in clinical research, visit NIH Clinical Research Trials and You. Learn about clinical trials currently looking for people with neurocutaneous syndromes at Clinicaltrials.gov, a database of current and past clinical studies, some of which have research results.