Tuberous sclerosis

Tuberous sclerosis is a genetic condition and there is no cure. A person will never outgrow the disorder. Tuberous sclerosis can affect people very differently. Some people have significant symptoms in infancy and childhood, while others have very mild symptoms and go undiagnosed until adulthood. Tuberous sclerosis is a progressive disorder and specific symptoms may develop at different times during a person’s life. The tumors that people develop in tuberous sclerosis are not cancerous, meaning they don’t spread (metastasize) to other areas of the body. However, these tumors can slowly grow larger damaging the surrounding tissue and causing symptoms. The rate of growth of the tumors can different in one person when compared to another. According to the Tuberous Sclerosis Alliance, most people with the disorder will have a normal life expectancy.

In a family with tuberous sclerosis, genetic tests can be done to see whether other family members have the disorder. The fastest and simplest genetic test is to look for a known gene change causing TS in a specific family. If known, all siblings and other at-risk relatives can be tested for just that change. If a child is diagnosed with tuberous sclerosis, parents should undergo testing. Parents may have an altered TSC1 or TSC2, but may be undiagnosed because they have mild symptoms or they are mosaic for the disorder. Mosaicism is when an altered gene only appears in a percentage of a person’s cells. Sometimes, people are mosaic for a disorder and do not have any symptoms, but can potentially pass on the disorder to their children. If the underlying changes in the TSC1 or TSC2 genes are not known in a family, then molecular genetic testing, which are tests that look for changes to genes, can be performed on an affected individual.

A genetic counselor or medical geneticist with experience in tuberous sclerosis can provide advice about how a confirmed diagnosis can affect other family members. Medical geneticists can be found through the American College of Medical Genetics and a genetic counselor can be found through the National Society of Genetic Counselors.

Support groups are organizations that provide support, information, advice, referrals to physicians and medical centers, and up-to-date information on research and treatments. Support groups for tuberous sclerosis include the Tuberous Sclerosis Alliance in the United States, the Tuberous Sclerosis Association in the United Kingdom and the Tuberous Sclerosis Canada Sclerose Tubereuse.

There are also online communities for rare disorders such as RareConnect, RareShare, or Inspire, which allow individuals and parents to share experiences and advice about dealing with rare disorders.

For some families or individuals, the medical cost of tuberous sclerosis can be significant. Some families lack the resources necessary to provide for a chronically ill or disabled child. Some individuals with tuberous sclerosis may find it difficult to deal with the financial costs of their disorder. Families or individuals may have trouble finding or affording health insurance. There are several organizations that provide financial assistance. The Tuberous Sclerosis Alliance can provide advice and guidance in managing these issues.

The Social Security Administration provides disability benefits for people who qualify. Tuberous sclerosis is not listed in the publication called the Disability Evaluation Under Social Security, also called the "Blue Book." However, some people with tuberous sclerosis may have specific symptoms that do qualify.

The National Organization for Rare Disorders has links to organizations that can provide financial assistance.

The National Human Genome Research Institute has extensive information on finding financial aid for medical treatment and services.

Taking care of someone with a long-term or chronic condition can be tiring and challenging and this is no different for parents or other caregivers of people with tuberous sclerosis. Caregivers of children with tuberous sclerosis have been shown to have lower physical and mental health-related quality of life scores. Caregivers need to take care of themselves as well as the person who has tuberous sclerosis. If you are a caregiver in need of support, try to take time for yourself, set aside time for personal counseling, or look for other resources at the Caregiver Action Network. This organization works to improve the quality of life for people who care for loved ones with chronic conditions, disabilities, disease, or the frailties of old age. Support groups can also help provide support and advice for caregivers. Support groups for tuberous sclerosis include the Tuberous Sclerosis Alliance in the United States, the Tuberous Sclerosis Association in the United Kingdom and the Tuberous Sclerosis Canada Sclerose Tubereuse.

Parents of children with chronic illness often struggle with when and how to tell their child about the diagnosis. Tuberous sclerosis is highly variable. Some children will have significant problems and it will be obvious that they have a medical disease. Others may have milder symptoms. Some parents may be unsure when to tell their child that they have a rare disorder. Most studies show that waiting to tell a child about a chronic or lifelong illness causes feelings of betrayal and anger. Additionally, keeping a diagnosis secret for too long has been shown to have an adverse effect on well-being throughout the person’s life. Parents should talk to their pediatrician, a therapist or a genetic counselor about the best ways and time to talk to their child about diagnosis.

The Tuberous Sclerosis Alliance has advice on how to tell a child about their diagnosis including information on how families have handled this issue in the past. Global Genes, a rare disease advocacy organizations, has a RARE Toolkit that discusses how to explain a disease to the child.

Tuberous sclerosis is often called tuberous sclerosis complex. It is typically abbreviated as TS or TSC.

There are a variety of tests a doctor may do to confirm a diagnosis of tuberous sclerosis (TS). Typically, a diagnosis of TS begins with a physical exam looking for features such as small tumors or characteristic TS skin findings. Doctors may also order testing such as a magnetic resonance imaging (MRI) of the brain or abdomen or echocardiogram of the heart to look for benign tumors or cysts. They may also order an electroencephalogram (EEG) to detect subclinical seizure activity. Subclinical means that a person is experiencing seizures, but they are so small that there are no obvious outward signs. There may also be an neuropsychiatric evaluation to identify intellectual disability or behavioral issues.

Once a clinical diagnosis of TS is suggested or there is TS in the family, molecular genetic testing can also be used to confirm a diagnosis of tuberous sclerosis. These tests involve studying the TSC1 or TSC2 genes for changes that can cause TS. This can include sequence analysis, where a part or sequence of DNA within a gene is examined, or gene-targeted deletion/duplication analysis, where missing or extra regions of DNA are looked for within a specific gene. Molecular genetic testing must be done at specialized laboratories.

To find a genetic medical professional nearby who can discuss information and testing, a listing of medical geneticists can be found at the American College of Medical Geneticists website and genetic counselors can be found on the National Society of Genetic Counselors website.

Complications in tuberous sclerosis (TS) can be increased when individuals living with TS smoke cigarettes or take estrogen based medicines. Additionally, the removal of a kidney surgically (nephrectomy) can lead to worsening TS issues.

Doctors will often use the term hamartoma when talking about the tumors that form in people with tuberous sclerosis. Hamartoma is a general term. It means that a tumor is made up of the cells normally found in the part of the body where the hamartoma is located. Hamartomas are benign (noncancerous) and do not spread to other areas of the body. They can grow larger and damage the surrounding tissues and organs.

Some people will develop tumors in the brain called glioneuronal hamartomas, subependymal giant cell astrocytomas (SEGAs), or cortical dysplasia. A common tumor of the kidneys is called an angiomyolipoma, which is made up of fat, blood vessels and smooth muscles cells. Some people have a tumor in the heart called a rhabdomyoma. Sometimes this tumor can form before a person is born and can be seen on a routine ultrasound of a developing fetus during pregnancy.

Nearly all people have problems affecting the skin. Infants may have white patches or spots on their skin. The affected skin may be lighter than the surrounding skin and can easily be missed on infants with fair skin. Between 3 and 5 years old, some children develop small bumps or red spots called angiofibromas. Angiofibromas most often appear on the face. Some people develop a dimpled, rough skin rash or patch of skin called a shagreen patch. There may be raised, thickened patches of skin called fibrous plaques.

These are some of the more common tumors associated with tuberous sclerosis. Talk to your doctors and entire medical team about how tuberous sclerosis is affecting your or your child.

Tuberous sclerosis (TS), also known as tuberous sclerosis complex, is a rare genetic condition. The main features of TS are the formation of benign (not cancerous) tumors throughout the body, most often in the brain, eyes, heart, kidneys, skin and lungs. These tumors are often referred to as hamartomas. Although these tumors are benign, they can cause problems because they grow and can damage nearby organs or structures in the body. Most individuals living with TS also have skin findings as well such as patches of very light-colored skin, areas of raised and thickened skin, and growths under the nails. Having said this, the way in which TS affects one person can be very different from how it affects another person. The signs and symptoms will depend on the number and severity of the organs affected by the condition. For example, some people living with TS will have neurological problems such as seizures beginning in infancy, while others may only have problems with their skin or their kidneys.

TS is caused by a change (mutation) in one of two genes: TSC1 or TSC2 . These changes can be inherited or can occur spontaneously (without a family history of the disorder). A genetic counselor or medical geneticist can help families understand this disorder. The Tuberous Sclerosis Alliance in the United States, the Tuberous Sclerosis Association in the United Kingdom and the Tuberous Sclerosis Canada Sclerose Tubereuse provide information and support.

Tuberous sclerosis is a highly variable disorder. This means the way the disorder affects one person can be very, very different from how it affects another person. This is true for people in the same family and even true for identical twins. This makes it very difficult to make broad statements about life expectancy for a person who is diagnosed with tuberous sclerosis. The disorder can cause mild symptoms and some people may go undiagnosed well into adulthood. In other instances, it can cause severe complications including intellectual disability, seizures that are resistant to treatment, and kidney problems. According to the Tuberous Sclerosis Alliance, most people with the disorder will have a normal life expectancy. However, every person is unique. People with tuberous sclerosis should discuss their individual situation with their or their child’s doctors and entire medical team. Genetic counselors can offer information about how a gene change (mutation) in the TSC1 or TSC2 genes can cause tuberous sclerosis and how it affects the immediate family. To find a genetic counselor near you, visit the Find a Genetic Counselor tool on the National Society of Genetic Counselors website.

Tuberous sclerosis (TS) is caused by a change (mutation) in one of two genes: TSC1 or TSC2 . Sometimes the change in the TSC1 or TSC2 gene is inherited from a parent. Other times a gene change happens randomly and the person with the gene change is the first in the family to have TS. A "first in the family" gene change is called a de novo mutation.

To find a medical professional nearby who can discuss information about gene changes in tuberous sclerosis, a listing of medical geneticists can be found at the American College of Medical Geneticists website and genetic counselors can be found on the National Society of Genetic Counselors website.

Tuberous sclerosis is caused by a change (mutation) in one of two genes: TSC1 or TSC2 . Not all changes in a gene necessarily cause disease. If a change is known to result in tuberous sclerosis, it is known as a pathogenic or disease-causing variant. More than 500 different changes (mutations) in these two genes have been identified as disease-causing in tuberous sclerosis. Sometimes gene changes are found and scientists are unsure what it means, either because it has not been found before or has only been found in a few people. This is known as a variant of unknown significance. If you have a variant of unknown significance in the TSC1 or TSC2 genes, talk to your doctor about further testing that may help find out whether the gene change is pathogenic or not. A genetic counselor may also be able to help you review your test results. To find a genetic counselor near you who can discuss testing and results, visit the National Society of Genetic Counselors Find a Genetic Counselor website.

Rare diseases that affect multiple organ systems like tuberous sclerosis (TSC) can benefit from a multidisciplinary approach. This approach involves healthcare professionals with specialized skills and expertise. They work together to make treatment recommendations and to provide quality care of individuals and families. Depending upon the specific symptoms in an individual, a multidisciplinary team may include:

It is recommended that children and adults with tuberous sclerosis received psychosocial support. This means that they should receive help for any psychological or social problems they may have. Tuberous sclerosis can cause children and adults to have to alter their life and can lead to feelings of isolation, anxiousness, depression and frustration. These are normal feelings for individuals and families dealing with a chronic illness. Talk to your doctor and medical team about how to deal with such issues. For behavioral problems, or depression and other mood issues, counseling by a psychologist or being treated by a psychiatrist may be helpful as well. It is also beneficial to talk to other people and families that are dealing with the challenges of tuberous sclerosis. Support groups can provide support and networking opportunities. Support groups for tuberous sclerosis include: the Tuberous Sclerosis Alliance in the United States, the Tuberous Sclerosis Association in the United Kingdom and the Tuberous Sclerosis Canada Sclerose Tubereuse.

When infants and children have a chronic disorder like tuberous sclerosis, it demands a lot of time and focus from parents. As with similar disorders, it is easy for healthy siblings to feel as if they have been pushed aside. Although studies have shown that siblings of children with chronic illness tend to develop strong levels of compassion and empathy, these studies have also shown that siblings can develop feelings of jealousy, anger, and high levels of anxiety. Parents can work with siblings by having clearly defined roles and responsibilities within the family structure. Siblings can help with the care of their sick sibling. Parents are encouraged to make time for activities, especially for healthy siblings, and to talk with and encourage healthy siblings to address their concerns and feelings. Some children may benefit from support outside of the immediate family including therapists or doctors. The Sibling Support Project is a nonprofit organization that serves the concerns and needs of siblings of people with special health, developmental, and mental health needs.

Tuberous sclerosis can includes health issues in many parts of the body including:

Tuberous sclerosis (TS) is a highly variable disorder. This means how the medical issues affect one person can be very different from how it affects another person. This is true for people in the same family. The potential list of symptoms for tuberous sclerosis is long, but an individual may have many symptoms or only a few.

The main symptom is the formation of benign tumors. Benign tumors are not cancerous; they do not spread (metastasize) to other areas of the body. However, they can grow and damage the surrounding organs and tissue. The skin, brain, eyes, heart, kidneys, and lungs are the most commonly affected organs. However, any organ system can be involved.

Nearly all people have problems affecting the skin. Infants may have white patches or spots on their skin. The affected skin may be lighter than the surrounding skin and can easily be missed on infants with fair skin. Between 3 and 5 years old, some children develop small bumps or red spots called angiofibromas. Angiofibromas most often appear on the face. Some people develop a dimpled, rough skin rash or patch of skin called a shagreen patch. There may be raised, thickened patches of skin called fibrous plaques.

In some people, the central nervous system is affected. Benign tumors in the brain can also push against, or compress, brain tissue causing pressure on the brain or damage to brain tissue. This can cause seizures in infants, although seizures can first occur at any age. In some infants and children, there may be delays in reaching developmental milestones, and can lead to behavioral, psychiatric, sleep disorders, and intellectual difficulties. Some children may have autistic-like behavior, attention deficit hyperactivity disorder (ADHD), and disruptive behaviors or emotional problems. Some will have intellectual disability or experience learning disabilities. Some children have hydrocephalus, a condition where cerebrospinal fluid, the clear fluid that surrounds the brain and spinal cord, abnormally builds up in the brain. This puts pressure on the brain and can cause a variety of symptoms.

Many people with tuberous sclerosis will have tumors form in the kidneys. One type of tumor is called an angiomyolipoma. Over time, these tumors will grow larger and more may form as children age. These tumors may not cause symptoms or they can cause pain and worsening function of the kidneys. They can rupture causing bleeding that potentially can become life-threatening. Some people may develop cysts on the kidneys.

Some adults with tuberous sclerosis will develop a lung disorder called lymphangioleiomyomatosis or LAM. This is more common in women. LAM can cause difficult breathing or coughing, particularly following exercise or other physical activity. The disorder slowly gets worse and can cause a collapsed lung or fluid to accumulation around the lungs. In women, LAM tends to worsen during pregnancy.

Small benign tumors may form on the retina, which is the thin layer of nerve cells lining the back of the eyes. The retina senses light and converts it to nerve signals that travel to the brain along the optic nerve allowing us to see. They usually do not cause symptoms or affect vision.

A tumor in the heart, called a rhabdomyosarcoma, can form. This tumor usually affects infants or young children. This tumor can sometimes be detected before birth. These tumors usually shrink on their own and disappear without causing problems. However, sometimes they can interfere with or obstruct blood flow in the heart. This can cause problems like irregular heartbeats and can require treatment.

These are just some of the issues that tuberous sclerosis can cause. Other organs symptoms can be affected as well. The specific symptoms relate directly to the organ systems that are affected. Support groups offer extensive information about tuberous sclerosis. These groups include: the Tuberous Sclerosis Alliance in the United States, the Tuberous Sclerosis Association in the United Kingdom and the Tuberous Sclerosis Canada Sclerose Tubereuse.

After an initial diagnosis of tuberous sclerosis (TSC), your doctor will take a comprehensive medical history. Several different tests may be run to see what organ systems of the body are affected. Doctors recommend that all newly-diagnosed individuals be evaluated for TSC-associated neuropsychiatric disorders (TANDs) including autistic-behaviors, aggressive behaviors, intellectual disability, or psychiatric problems. People with TSC should receive information about their disorder and work with doctors to develop and an overall treatment plan. Doctors may recommend testing family members to see whether they also have the disorder.

The best way to obtain the most accurate, current, clear, and comprehensive information is to be seen at a TSC clinic. These are genetic centers that specialize in the treatment of patients with TSC. At most centers, you will see a medical geneticist, genetic counselor, and nurse who work as a team to answer your questions, discuss testing, identify your at-risk family members, and develop a comprehensive evaluation and treatment plan for you. A TSC clinic will work with your current doctors to organize the treatment, tests, and specialists you need. The Tuberous Sclerosis Alliance has a listing of TSC clinics in the United States.

Some children and adults with tuberous sclerosis (TS) have differences in how their brain functions– a combination of behavioral, psychiatric, intellectual, academic, neuropsychological, and psychological problems called TS-related neuropsychiatric disorders or TANDs. Such problems may include autistic-like behaviors, attention deficit hyperactivity disorder, sleep problems, disruptive behaviors, emotional problems, and learning and cognitive issues. Not everyone with TS develops these problems. In people who do, the specific problems and their severity can differ greatly. The Tuberous Sclerosis Alliance has information and support for people with tuberous sclerosis. The Arc, is an organization that provides support for people with intellectual and developmental problems.

Tuberous sclerosis is inherited in an autosomal dominant inheritance pattern which means that every first degree relative of an affected individual has a 50% chance of also having the condition. First degree relatives are siblings, children, and parents. Second degree relatives should have testing after first degree relatives are all tested.

In a specific example, let’s say 27-year-old Andrea has been diagnosed with tuberous sclerosis. Andrea has 3 children. EACH of her children has an individual 50% chance to also have it. Andrea has 2 siblings: one brother and one sister. EACH of her siblings has an individual 50% chance to also have it. Andrea’s mother has testing and is negative. This means that Andrea’s mothers side of the family does NOT need to have any more testing. Andrea’s father has testing and is positive. Each of Andrea’s father’s siblings should have testing as well, because they have an individual 50% chance of being positive as well. A genetic counselor can help individuals with TS understand the impact on family members and review testing options. To find a genetic counselor near you who can discuss testing and results, visit the National Society of Genetic Counselors Find a Genetic Counselor website.

Tuberous sclerosis is a genetic disorder. The main symptom is the development of a variety of benign (noncancerous) tumors. Tuberous sclerosis is not a form of cancer in the traditional sense. Most of the tumors in tuberous sclerosis do not become cancerous and spread (metastasize) to other areas of the body. Symptoms occur because these benign tumors grow and begin to damage the surrounding tissue. People with tuberous sclerosis are at risk for developing certain types of cancer, particularly those affecting the kidneys, brain and soft tissues of the body. Soft tissue is tissue of the body that does not harden (calcify) including ligaments, tendons, fat, skin, and muscle. Some tumors associated with this disorder can become cancerous including angiomyolipomas in the kidneys and subependymal giant cell tumors of the brain. Adults are at a greater risk of developing a form of kidney cell cancer called renal cell carcinoma.

Tuberous sclerosis (TS) is not one of the disorders that is automatically tested for at birth. Accordingly, TS often goes undiagnosed until young adulthood. However, if a baby has health problems such as a a benign heart tumor called a rhabdomyosarcoma that could be caused by tuberous sclerosis, genetic testing is available. The easiest way to find testing for the disorder is to talk with the pediatrician or primary doctor about a referral for a genetics evaluation.

Further information about genetic testing for TS in your area can also be obtained through a genetic counselor. To find a genetic counselor visit the National Society of Genetic Counselors Find a Genetic Counselor website.

More Information about newborn screening programs can be found at Save Babies Through Screening Foundation or Baby’s First Test.

There are about 60 studies involving tuberous sclerosis listed on clinicaltrials.gov, a government website that provides regularly updated information about federally and privately supported clinical trials. This is not necessarily an exhaustive list of current research. Current studies are looking at the natural history of kidney problems in tuberous sclerosis; several potential drug therapies; trying to determine if certain gene changes in the TSC1 and TSC2 genes are more likely to cause certain symptoms; evaluating autism and intellectual issues in tuberous sclerosis; and other studies.

For the most up-to-date list, contact clinicaltrials.gov and search for tuberous sclerosis.

Some women with tuberous sclerosis are at risk of developing a lung disorder called lymphangioleiomyomatosis (LAM). Doctors believe that estrogen is a factor in this lung disorder developing. Because of the risk of lung disease, adolescent and adult females should avoid estrogen use and smoking.

People with tumors in the kidney should avoid undergoing surgical removal of a kidney (called a nephrectomy) because there is a risk of complications in people with tuberous sclerosis.

Most individuals with tuberous sclerosis develop benign tumors of the skin. Doctors recommend that these people take precautions to protect themselves from the sun. Many people have hypopigmented macules, which are white patches or spots that are lighter than the surrounding skin. These macules are susceptible to sunburns.

A patient registry is a database set up by researchers that contains information about patients with a particular disorder or group of disorders. This information helps researchers learn about a disorder, plan or study treatments, how a disorder progresses or affects people and other information. Patient registries require that patients either directly or through their doctor submit personal information. There is an international patient registry for tuberous sclerosis called TOSCA, or TuberOus SClerosis registry to increase disease Awareness. The Tuberous Sclerosis Alliance has a natural history database that collects clinical data about the disorder throughout a person’s lifetime. This information is made to investigators.

Talk to a genetic counselor about the pros and cons of participating in a patient registry.

There is no cure for tuberous sclerosis. There are many different treatments to help manage the symptoms of the disorder. Specific treatments depend on many different factors including what organ systems are affected and what symptoms have developed, how old a patient is, a person overall health and personal preference. The care of people with tuberous sclerosis is high individualized because the disorder can affect people very differently.

The 2012 International Tuberous Sclerosis Complex Consensus Conference published guidelines for the treatment and management of people with tuberous sclerosis. Treatments include medications, surgery, and supportive services including occupational, physical and speech therapy. Sometimes remedial education and rehabilitative and behavioral therapy may be recommended.

In 2018, the U.S Food and Drug Administration (FDA) approved everolimus (Afinitor®) for the treatment of children and adults with tuberous sclerosis (TS) and partial-onset seizures. Everolimus is also approved by the FDA for the treatment of adults with several other tumors with and without TS. Everolimus is an mTOR inhibitor. The mTor pathway is a series of biochemical reactions that help to regulate cell growth, spread, and survival. This pathway is overactive in people with tuberous sclerosis and drugs like everolimus slow down (or inhibit) these chemical reactions.

Sometimes there is no history of tuberous sclerosis in a family when a person is diagnosed. This is because sometimes an alteration (mutation or other change) to the gene can also happen at random for no known reason. This is called a de novo mutation. Sometimes, one parent of a child with tuberous sclerosis has a very mild form of the disorder and does not know it until testing is done after the child is diagnosed. Sometimes, this is because of mosaicism. Mosaicism is when a person has an altered gene in some of their cells, but not all of them. They may have very mild symptoms or no symptoms of the disorder, but can pass the disorder on to their children.

Talk to a genetic counselor to learn more about the genetics of tuberous sclerosis. To find a genetic counselor near you, visit the Find a Genetic Counselor tool on the National Society of Genetic Counselors website.

Tuberous sclerosis is a rare disorder. Rare disorders often go unrecognized or misdiagnosed and the incidence and prevalence of individual rare disorders is often unclear or unknown. Prevalence is the measurement of all individuals affected by the disease at a particular time. Incidence is the number of new people with a disorder or newly-diagnosed. One estimate places the incidence at one in 6,000 newborns in the United States. Overall, approximately 40,000 and 80,000 people in the U.S. have tuberous sclerosis. As many as 2,000,000 million people worldwide may have the disorder. Tuberous sclerosis affects both men and women, and all ethnic and racial groups.

Humans inherit two copies of most of genes from their parents. One copy comes from the mother and the other copy comes from the father. In tuberous sclerosis, only one parent must pass along a nonworking copy of the TSC1 or TSC2 gene for the disorder to develop. Because of this, tuberous sclerosis is inherited in what is called an autosomal dominant pattern. This means a person only needs only one altered gene to have the disorder. If one parent has an altered TSC1 or TSC2 gene, which causes their disease, then each of their children will have a 50% chance of inheriting that mutation and developing tuberous sclerosis.

In some families, a child will develop tuberous sclerosis and be the first person in the family with the disorder. This occurs because of a de novo mutation, which means that the altered gene occurs randomly. The child who carries the altered gene can pass on the alteration in an autosomal dominant manner. In most families with a child with a de novo mutation, the likelihood of having another child with tuberous sclerosis is extremely low.

Tuberous sclerosis is inherited in autosomal dominant manner. This is one way a disorder or trait can be passed down through a family. The first word, "autosomal," means the altered gene is on a chromosome that both males and females carry. Therefore, tuberous sclerosis can affect either gender. The second word, "dominant," means a gene change in one copy of a person’s TSC1 or TSC2 gene is enough for them to develop the disease.

Humans have two copies of every gene – one from our mother and one from our father. In a dominant condition, only gene copy of them needs to have a disease-causing change to lead to the condition. This means that if a parent carries a changed TSC1 or TSC2 gene, they have a 50% chance to pass the affected gene to each of their offspring, regardless of gender. This also means that there is a 50% chance that an affected parent would not pass this on to their children.

In some people, there is no previous history of tuberous sclerosis in the family. The altered TSC1 or TSC2 gene occurs randomly. This is also called a de novo mutation. The altered gene in the child can be passed on as an autosomal dominant trait. In most families with a child with a de novo mutation, the likelihood of having another child with tuberous is extremely low. One estimate states that 80% of people with tuberous sclerosis have a de novo mutation. A mutation in the TSC2 gene is about four times more common than a mutation in the TSC1 gene.

Individuals who have a family member with tuberous sclerosis and wish to learn more about the genetics of the condition can meet with a genetic counselor to discuss testing options.

Tuberous sclerosis is caused by a change in one of two genes: TSC1 or TSC2 . These genes are tumor suppressor genes. Tumor suppressor genes help to control the growth and life cycle of cells. Specifically, they can influence how cells grow and divide to ensure that cells die off at the proper time. The TSC1 gene produces a protein called hamartin. The TSC2 gene produces a protein called tuberin. These proteins are involved in slowing down or inhibiting the mTor pathway. Chemical pathways are a series of complex chemical interactions that occur in the body and are critical for normal human development. The mTor pathway produces mammalian target of rapamycin or mTOR, which is a specialized protein called an enzyme. This enzyme is involved cell growth, spread, and survival. The changes in the TSC1 and TSC2 genes results in this pathway being overactive, leading to more cell growth, spread and survival of certain cells. Eventually, this overgrowth leads to the development of the benign tumors that form in people with tuberous sclerosis.

Individuals with tuberous sclerosis and parents of children with the disorder often struggle with when and how to tell people about the diagnosis. Tuberous sclerosis is highly variable. Some children or adults will have significant problems and it will be obvious that they have a medical disorder. Other children or adults may have milder symptoms. It may not be readily apparent that they have a disorder. Some individuals or parents may be unsure when to tell relatives, friends or other people that they have a rare disorder. Individuals and parents should talk to their pediatrician, a therapist or a genetic counselor about the best ways and time to talk to their child about diagnosis.

The Tuberous Sclerosis Alliance has advice on how deal with a diagnosis of tuberous sclerosis including explaining how other families have handled these issues. Global Genes, a rare disease advocacy organizations, has a RARE Toolkit that discusses how to explain a rare genetic diagnosis to family members, children and friends.

Tuberous sclerosis is a rare disease and often receiving a proper diagnosis can be a challenge. Usually, doctors suspect tuberous sclerosis because of specific symptoms or because of a known family history of the disorder. In 2012, the Tuberous Sclerosis Complex Conference published diagnostic criteria for the disorder. This document separates the symptoms into major and minor criteria. If people have two major criteria or one major criteria and two or more minor criteria, doctors may conduct tests to see if they have tuberous sclerosis.

Major criteria include small patches of white skin or skin that is lighter than the surrounding skin (hypopigmented macules), seizures, autistic behaviors, certain benign tumors of the brain or kidneys, or a heart tumor called a rhabdomyosarcoma. The full document which explains all the major and minor criteria is available online at: Tuberous Sclerosis Complex Diagnostic Criteria Update: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference.

A doctor will do a complete physical examination and talk about a patient and family’s medical history. Tuberous sclerosis can be confirmed by genetic testing. These tests involve studying TSC1 and TSC2 genes for changes (mutations or other changes) that are known to cause the disorder. If tuberous sclerosis is confirmed, a doctor may order additional tests to see what organ systems are involved, to what extent they are involved, and how far along the disorder is.

If you believe that you or your child has tuberous sclerosis, you can request or seek out a referral to a Tuberous Sclerosis Complex (TSC) Clinic or genetics clinic. The Tuberous Sclerosis Alliance has information on these clinics. The Genetics and Rare Diseases Information Center provides information on how to find healthcare professionals with experience in specific conditions, specialty treatment centers, genetics clinics, and researchers who are studying a specific condition.

To learn about ongoing clinical research into tuberous sclerosis, ask a physician who specializes in the disorder. Genetic counselors and medical geneticists are also excellence sources of information about ongoing clinical trials and can offer advice about the pros and cons about participating in such a trial.

Ongoing studies for tuberous sclerosis can also be found on clinicaltrials.gov, a service of the U.S. National Institutes of Health. In Europe, the EU Clinical Trial Register performs a similar service.

Support groups also have information about ongoing clinical trials as well as information and advice about participating in clinical trials. Support groups for tuberous sclerosis include the Tuberous Sclerosis Alliance in the United States, the Tuberous Sclerosis Association in the United Kingdom and the Tuberous Sclerosis Canada Sclerose Tubereuse provide information and support.

The best way to obtain the most accurate, current, clear, and comprehensive information on tuberous sclerosis (TSC) is to be seen at a TSC Center of Excellence. These are genetic centers or clinics that specialize in the treatment of patients with tuberous sclerosis. At most centers, you will see a medical geneticist, genetic counselor, and nurse who work as a team to answer your questions, discuss testing, identify your at-risk family members, and develop a comprehensive evaluation and treatment plan for you. A Center will work with your current doctors to organize the treatment, tests, and specialists you need. The Tuberous Sclerosis Alliance has a listing of TSC clinics in the United States.

Many children with tuberous sclerosis find it challenging when it’s time to move (transition) from pediatric to adult care services. One big change is leaving a doctor with whom you have a long-standing relationship, a doctor who is familiar with both your condition and yourself. It can feel like ‘starting over’ as you’ll begin to work with new doctors and a new medical team. Another challenge in moving to adult care is that young adults must take greater responsibility for their health. They must manage their disorder and manage their therapy. They must bear greater responsibility for decisions concerning their health. Some hospitals have programs to help children with chronic disease transition to adult care services. Some families create a transition plan to help children move from pediatric care to adult care.

The Tuberous Sclerosis Alliance has information and advice about how young adults can take charge of their lives and manage their diagnosis. Global Genes, an organization that provides support and information for rare disorders, has a RARE Toolkit about young adults gaining independence and taking command of their healthcare.

Tuberous sclerosis is a highly variable disorder. Some people do not develop symptoms in childhood or only have mild symptoms. These children can attend school and excel like all children. However, some children may have seizures, delays in reaching developmental milestones and other neurological problems.
Because they have a chronic illness, can experience learning disabilities, and some children have physical limitations, they may need special accommodations. Because they may need special accommodations in school, they may eligible for an individual education plan (IEP) or a 504 plan. An IEP is a document that helps to guide the education of a child with a disability or special needs. The plan is individualized for each student. A 504 plan ensures that students with disabilities can fully participate in school and have access to the same educational opportunities as all children. Parents are encouraged to provide a school with a packet of information on tuberous sclerosis and to work with school officials including teachers, nurses, psychologists, the principal, and other professionals.

The U.S. Department of Education has information on individual education plans and on 504 plans. Global Genes, a rare disease advocacy organization, has a RARE Toolkit that advises parents on advocating for their children at their school.

The Tuberous Sclerosis Alliance runs an Educator Mentor Program (EMP) that was developed to support school systems in understanding the learning needs of children with TSC. This program includes administrators, therapists, physiologists, and teachers from pre-kindergarten to college level having experience with tuberous sclerosis. They provide one-on-one support to any professional in the school system needing education and support in understanding the educational complexities of the disorder. The Tuberous Sclerosis Alliance provides information and advice on how to deal with school issues in children with tuberous sclerosis.

The incidence of tuberous sclerosis may be as high as 1:5,800 live births. A high mutation rate (1:250,000 per gene per generation) is estimated.

Some children and adults with tuberous sclerosis (TSC) will have some specific neuropsychiatric problems. This is called TSC-related neuropsychiatric disorders or TANDs. This includes a collective group of behavioral, psychiatric, intellectual, academic, neuropsychological and psychological problems. Such problems may include autistic-like behaviors, attention deficit hyperactivity disorder, sleep problems, disruptive behaviors, emotional problems, and learning and cognitive issues. Children and adults should be screened every year for TANDs.

Treatment for TANDs depends on how an individual person is affected. This can include occupational, physical and speech therapy; rehabilitative and behavioral therapy; special remedial education; vocational and social support; and psychiatric evaluation. The Tuberous Sclerosis Alliance has information and support for people with tuberous sclerosis. The Arc, is an organization that provides support for people with intellectual and developmental problems.

In 2018, the U.S Food and Drug Administration (FDA) approved everolimus (Afinitor®) for the treatment of children and adults with tuberous sclerosis (TS) and partial-onset seizures. Everolimus is also approved by the FDA for the treatment of adults with several other tumors with and without TS. Everolimus is an mTOR inhibitor. The mTor pathway is a series of biochemical reactions that help to regulate cell growth, spread, and survival. This pathway is overactive in people with tuberous sclerosis and drugs like everolimus slow down (or inhibit) these chemical reactions.Researchers are studying this drug and drugs like this one to see if they can improve mental and behavioral issues in tuberous sclerosis.

Some people with tuberous sclerosis may develop lung problems that are virtually identical to a lung disorder called lymphangioleiomyomatosis or LAM. This is more common in younger women. LAM can cause difficult breathing or coughing, particularly following exercise or other physical activity. The disorder slowly gets worse and can cause a collapsed lung or fluid to accumulation around the lungs. In women, LAM tends to worsen during pregnancy.

In 2018, the U.S Food and Drug Administration (FDA) approved everolimus (Afinitor®) for the treatment of children and adults with tuberous sclerosis (TS) and partial-onset seizures. Everolimus is also approved by the FDA for the treatment of adults with several other tumors with and without TS. Everolimus is an mTOR inhibitor. The mTor pathway is a series of biochemical reactions that help to regulate cell growth, spread, and survival. This pathway is overactive in people with tuberous sclerosis and drugs like everolimus slow down (or inhibit) these chemical reactions.

Some doctors believe that female hormones like estrogen play a role in the development of LAM in tuberous sclerosis. This is because young women of childbearing age are most likely to develop this problem. Some doctors will recommend drugs that lower the levels of estrogen in the body. Such treatment has helped some women, but not others and no evidence proving a link between estrogen and LAM has been found yet.

Sometimes, lung function in people with tuberous sclerosis is bad enough that they require oxygen supplementation.

The most common kidney tumor is tuberous sclerosis is called an angiomyolipoma. These types of tumors are made up of fat, blood vessels and smooth muscle cells. Over time, these tumors will grow larger and more may form as children age. Many people will not need any treatment as these tumors may not cause symptoms. Sometimes, they can cause pain and worsening function of the kidneys, or they can rupture causing bleeding that potentially can become life-threatening.

In 2018, the U.S Food and Drug Administration (FDA) approved everolimus (Afinitor®) for the treatment of children and adults with tuberous sclerosis (TS) and partial-onset seizures. Everolimus is also approved by the FDA for the treatment of adults with several other tumors with and without TS. Everolimus is an mTOR inhibitor. The mTor pathway is a series of biochemical reactions that help to regulate cell growth, spread, and survival. This pathway is overactive in people with tuberous sclerosis and drugs like everolimus slow down (or inhibit) these chemical reactions. Doctors are studying these types of drugs to see if they are effective in treating other symptoms of tuberous sclerosis ilke those in the kidney.

Sometimes, doctors may recommend embolization, a type of surgery where doctors prevent the blood flow to a certain area of the body. Embolization blocks the blood supply a tumor needs to grow and survive. The tumor will shrink. Doctors may then give corticosteroids to reduce inflammation and remove the shrunken tumor surgically.

Less often, there may be other problems with the kidneys that require different treatments. Talk to your or your child’s doctor and entire medical team, which should include a specialist who is trained in diagnosing and treating the kidneys (nephrologist), about how tuberous sclerosis can affect the kidneys.

About 80% of people with tuberous sclerosis will develop seizures at some point during their lives. If people have seizures, they may be treated with anti-seizure drugs. These drugs are sometimes called anti-convulsants. There are many kinds of anti-convulsants. Controlling seizures can be difficult especially in children. Sometimes drugs don’t work, or they work for a little while and then stop working. Children may have different types of seizures and some drugs may work better for certain types of seizures. A specific seizure, called infantile spasms, may be treated by vigabatrin (Sabril®) or corticotrophic hormone (Acthar® gel).

In 2018, the U.S Food and Drug Administration (FDA) approved everolimus (Afinitor®) for the treatment of children and adults with tuberous sclerosis (TS) and partial-onset seizures. Everolimus is also approved by the FDA for the treatment of adults with several other tumors with and without TS. Everolimus is an mTOR inhibitor. The mTor pathway is a series of biochemical reactions that help to regulate cell growth, spread, and survival. This pathway is overactive in people with tuberous sclerosis and drugs like everolimus slow down (or inhibit) these chemical reactions.

If drugs do not stop the seizures, physicians have tried the ketogenic diet, vagus nerve stimulation, and surgery. The ketogenic diet is a high-fat, low-carbohydrate diet that has shown to be effective in reducing seizures in some people. This diet is usually recommended for children if different anti-seizure medications have not worked. The Epilepsy Foundation has information on the ketogenic diet. Vagus nerve stimulation involves having a small device called a pulse generator implanted near the neck to stimulate the vagus nerve. This nerve is the longest of the 12 cranial nerves. The generator sends electrical impulses through the vagus nerve to the brain to prevent seizures. Surgery can also be used to treat seizures in tuberous sclerosis that do not improve with drug treatment. This is especially true if a brain tumor is present.

Although brain tumors in tuberous sclerosis are benign (noncancerous), they can cause serious problems because they can grow and damage surrounding brain tissue. There are two main options for treating brain tumors. There is a drug called everolimus (Afinitor®) that can be used for people in certain situations or there is surgery.

In 2018, the U.S Food and Drug Administration (FDA) approved everolimus (Afinitor®) for the treatment of children and adults with tuberous sclerosis (TS) and partial-onset seizures. Everolimus is also approved by the FDA for the treatment of adults with several other tumors with and without TS. Everolimus is an mTOR inhibitor. The mTor pathway is a series of biochemical reactions that help to regulate cell growth, spread, and survival. This pathway is overactive in people with tuberous sclerosis and drugs like everolimus slow down (or inhibit) these chemical reactions.

In other situations, doctors may have to remove a brain tumor surgically. Sometimes, surgery is necessary because a tumor causes cerebrospinal fluid (the fluid that cushions the brain and spinal cord) to build up in the brain causing pressure. Surgeons will remove the tumor or may put in a shunt that will allow the fluid to drain out of the brain.

People with tuberous sclerosis will need to monitor their health. Periodic checkups will be necessary because benign tumors can form at any age and affect almost any organ system. Some symptoms may not develop until adulthood. Individuals and parents of affected child will work with their doctors and entire medical team to work out a schedule of what tests need to be done each year to ensure that any potential symptom of the disorder is detect as early as possible.

Some parents may choose to have their child tested for tuberous sclerosis before they are born. This is known as prenatal diagnosis. If the gene change(s) that cause tuberous sclerosis are known in a family, then molecular genetic testing (which can detect these changes) can be used for prenatal diagnosis. A sample of tissue can be taken from the placenta to test for changes in the TSC1 or TSC2 genes via chorionic villus sampling or amniocentesis.

Preimplantation genetic diagnosis (PGD) in which embryos can be genetically tested is also available. During this process, embryos are created through in vitro fertilization (IVF) by taking eggs from the mother and sperm from the father. The two are then combined in the laboratory. A few cells are removed from the embryo and are then tested to determine whether that specific embryo inherited the altered gene(s). Then, the family can choose to only have the embryos without tuberous sclerosis transferred to create the pregnancy.

It is important to understand that although tuberous sclerosis can be diagnosed before birth, the severity of the disorder cannot be determined. Tuberous sclerosis has a significant variability in expression with some people only mildly affected.

Talk to your doctor or a genetic counselor in your area to discuss the risks and benefits of prenatal diagnosis.

Tuberous sclerosis (TS) is the most common name for the condition although the expanded name "tuberous sclerosis complex" (TSC) is being used more frequently by doctors to capture the range of medical issues seen in TS. Other names that have been used include:

Support groups are organizations that provide support, information, advice, referrals to physicians and medical centers, and up-to-date information on research and treatments. Some support groups also help to put people and families together who have the same diagnosis so they can share their experiences. Support groups for tuberous sclerosis include the Tuberous Sclerosis Alliance in the United States, the Tuberous Sclerosis Association in the United Kingdom and the Tuberous Sclerosis Canada Sclerose Tubereuse.

The first few years of a child’s life are critically important to a child’s development. Some infants and children with tuberous sclerosis have significant problems including seizures, delays in reaching developmental milestones, learning disabilities and other issues.

States have federally-funded early intervention programs that support families that have concerns or issues with their children’s development up to the age of three. Some states will continue to offer early intervention programs beyond the age of three. Other states will transition a child into school-based programs that can be provided at home. In some states, a child may be eligible for early intervention services at no charge. Other states may charge a fee, depending on the agencies involved.

Talk to your doctor and medical team about early intervention programs in your state and whether these resources will appropriate and beneficial for your child. The Centers for Disease Control and Prevention (CDC) provides information about early intervention programs and assistance.