Tuberous Sclerosis Complex

What is tuberous sclerosis complex?

Tuberous sclerosis complex (TSC) is a rare genetic disease that causes non-cancerous tumors or lesions to grow in the brain and other areas of the body, including the eyes, lung, heart, kidneys, and skin. 

Brain lesions are areas of injury or damage to brain tissues. The three types of brain lesions seen in TSC are called cortical tubers, subependymal nodules (SEN), and subependymal giant-cell astrocytomas (SEGA), which develop from SEN. 

Symptoms of TSC 

For many people with TSC, symptoms begin in infancy or childhood. For others, symptoms may take years to develop. Symptoms vary greatly from person to person, depending on which parts of the body are affected. Common symptoms include: 

• Seizures, including infantile spasms, focal seizures, and tonic-clonic seizures. Children with TSC often experience different types of seizures.
• Kidney problems, such as cysts and angiomyolipomas (benign growths made of fatty tissue and muscle cells). While these rarely cause symptoms, they can grow so large that they cause pain or lead to internal bleeding or kidney failure.
• Developmental delay and TSC-associated neuropsychiatric disorders (TAND). TAND refers to a range of cognitive, behavioral, and psychiatric conditions such as aggression, anxiety, attention deficit hyperactivity disorder, learning difficulties, obsessive-compulsive disorder, and autism spectrum disorder (ASD) seen in people with TSC.
• Skin differences, including: white or lighter patches of skin (called ash leaf spots); raised red or darker spots or bumps on the face (called angiofibromas); areas of thick, pebbled skin on the lower back or neck (called shagreen patches); and small growths under the nails (called ungual or subungual fibromas).
• Lung lesions, including lymphangioleiomyomatosis (LAM), a rare lung disorder that mostly affects women of childbearing age or older. Many people with TSC have no symptoms of LAM, while others suffer with breathlessness, which can get worse over time and be severe.

Who is more likely to get tuberous sclerosis complex?

TSC is caused by variants (or mutations) in either the TSC1 or TSC2 gene. These genes provide instructions for making the proteins hamartin and tuberin, which help regulate cell growth and division. Scientists believe hamartin and tuberin help stop cell growth by silencing or interfering with the function of another protein called mTOR, which also plays a key role in cell growth. When mTOR is not regulated properly, abnormal cell development can lead to the production of enlarged cells like the ones seen in TSC brain lesions. 

Most cases of TSC are sporadic (developing on their own) due to new, spontaneous variations in TSC1 or TSC2—meaning neither parent has the disorder or the genetic variation(s). 

Some cases of TSC are inherited, meaning the mutated gene is passed down from a parent to their child. The inheritance is in an autosomal dominant pattern, meaning a person only needs to inherit one copy of the affected gene from either parent to have the disease. Children who inherit TSC may not have the same symptoms as their parent and may have either a milder or more severe form of the condition.

In rare instances, people may get TSC through a process called gonadal mosaicism. Even without a parent with mutations in the TSC1 or TSC2 genes, the child may have TSC because some of one parent's reproductive cells contains the genetic mutation without the other cells of the body being involved.

How is tuberous sclerosis complex diagnosed and treated?

Diagnosing TSC

Diagnosing TSC is based upon a review of the signs and symptoms, the person’s family history, and diagnostic testing. The tests used to diagnose TSC include CT (computed tomography) or MRI (magnetic resonance imaging), ultrasound, and electrocardiogram (EKG). Seizures and delayed development may be the first signs of TSC. A careful examination of the skin, nails, teeth, gums, and eyes for characteristic features of TSC also can help diagnose the disorder.

Genetic testing can help parents determine if they are carriers of one of the genes that cause TSC. A genetic counselor can provide information about the test and what the results could mean.

Learn more about neurological diagnostic tests and procedures.

Treating TSC

TSC is a lifelong condition. Currently there’s no cure, but there are treatments to help manage TSC symptoms. Since TSC is unique to each person, an individualized treatment plan will provide the best possible symptom management.

Antiseizure medications may help control seizures. Vigabatrin can help treat infantile spasms. The U.S. Food and Drug Administration (FDA) approved cannabidiol to treat seizures in people with TSC, except for babies younger than one year. Everolimus (an mTOR inhibitor) has also been approved to treat intractable seizures (those not well-controlled by medicine) as well as certain brain and kidney tumors associated with TSC. 

A topical rapamycin (an mTOR inhibitor) gel has been approved to treat facial angiofibromas, and oral rapamycin has been approved to treat LAM.

People may need surgery to control epilepsy in some cases, or to remove tumors from affected organs if the tumors or lesions keep the organs from working properly. If the person has severe and progressive lesions on their lungs, they may need supplemental oxygen therapy or lung transplantation.

Physical, occupational, speech, and behavioral therapy can help with developmental delays and learning disabilities. 

What are the latest updates on tuberous sclerosis complex?

NINDS, a component of the National Institutes of Health (NIH), is the leading federal funder of research on the brain and nervous system, including research on conditions such as TSC. NINDS conducts and supports new and innovative research to better understand, diagnose, and treat these disorders.

Scientists hope knowledge gained from this research may improve diagnostic and genetic testing for TSC and lead to new avenues of treatment, methods of prevention, and, ultimately, a cure.

NINDS-funded scientists are using animal models to understand the mechanisms that lead to epilepsy and TAND in TSC. In another study supported by NINDS, researchers hope to learn more about the cellular mechanisms that cause epilepsy, ASD, and the cognitive and learning problems that happen in people with TSC.

NIH-supported scientists are also using neurobehavioral assessments, electroencephalogram (EEG) data, and MRI to identify biomarkers (biological measures of a disease) and gain insight into certain features of TSC, including ASD and cognitive and learning problems. Information from this study may lead to the development of effective treatments and interventions for these conditions.

NIH's Rare Diseases Clinical Research Network (RDCRN) advances medical research on rare diseases by providing support for clinical studies. It facilitates collaboration, study enrollment, and data sharing. RDCRN includes the Developmental Synaptopathies Consortium which supports natural history, imaging, and biomarker identification for TSC and related neurodevelopmental disorders.

For more information on research about TSC, check NIH RePORTER, a searchable database of current and past research projects funded by NIH and other federal agencies. RePORTER also includes links to publications and resources from these projects.

For research articles and summaries on TSC, search PubMed, which contains citations from medical journals and other sites.

How can I or my loved one help improve care for people with tuberous sclerosis complex?

Consider participating in a clinical trial, so clinicians and scientists can learn more about TSC and related disorders. Clinical research with human study participants helps researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease.

All types of participants are needed—those who are healthy or may have an illness or disease—of all different ages, sexes, races, and ethnicities. This helps make sure 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 the NINDS Clinical Trials site and NIH Clinical Research Trials and You. Learn about clinical trials currently looking for people with TSC at ClinicalTrials.gov, a searchable database of current and past federal and private clinical studies and research results.

Learn about related topics

• Epilepsy and Seizures