Tuberous Sclerosis Complex

Approved by the Cancer.Net Editorial Board, 11/2022

What is tuberous sclerosis complex?

Tuberous sclerosis complex (TSC) is a hereditary condition associated with changes in the skin, brain, kidney, and heart. Seizures are a frequent complication, and some people with TSC have learning disabilities.

Skin changes are the most noticeable sign of TSC and appear in nearly all people with the condition. While the skin changes do not have serious medical consequences, they can affect a person’s appearance. There are multiple features that have been associated with TSC. The number of features and the severity of symptoms can vary among people with TSC, even within the same family. More information about the features of TSC is below.

Although the overall cancer risk associated with TSC is low, people with TSC do have an increased risk of a specific type of brain cancer called giant cell astrocytoma and an increased risk of kidney cancer.

What causes TSC?

TSC is a genetic condition. This means that the cancer risk and other features of TSC can be passed from generation to generation in a family. So far, 2 genes have been linked to TSC, called TSC1 and TSC2. A mutation (alteration) in either of these genes gives a person an increased risk of developing kidney cancer and other symptoms of TSC. Research is ongoing to learn more about TSC, because some people with TSC may not have either of these known genetic mutations.

How is TSC inherited?

Normally, every cell has 2 copies of each gene: 1 inherited from the mother and 1 inherited from the father. TSC follows an autosomal dominant inheritance pattern, in which case a mutation happens in only 1 copy of the gene. This means that a parent with a gene mutation may pass along a copy of their normal gene or a copy of the gene with the mutation. Therefore, a child who has a parent with a mutation has a 50% chance of inheriting that mutation. A brother, sister, or parent of a person who has a mutation also has a 50% chance of having the same mutation. However, if the parents test negative for the mutation (meaning each person’s test results found no mutation), the risk to the siblings significantly decreases but their risk may still be higher than an average risk.

Options exist for people interested in having a child when a prospective parent carries a gene mutation that increases the risk for this hereditary cancer syndrome. Preimplantation genetic diagnosis (PGD) is a medical procedure done in conjunction with in-vitro fertilization (IVF). It allows people who carry a specific known genetic mutation to reduce the likelihood that their children will inherit the condition. Eggs are removed and fertilized in a laboratory. When the embryos reach a certain size, 1 cell is removed and is tested for the hereditary condition in question. The parents can then choose to transfer embryos which do not have the mutation. PGD has been in use for over 2 decades, and it has been used for several hereditary cancer predisposition syndromes. However, this is a complex procedure with financial, physical, and emotional factors to consider before starting. For more information, talk with an assisted reproduction specialist at a fertility clinic.

How common is TSC?

It is estimated that about 1 in 6,000 people has TSC, and there are about 1 million people with TSC in the world. As many as 60% of people with TSC do not have any family history of the condition; they have a de novo (new) mutation in the TSC1 or TSC2 gene.

How is TSC diagnosed?

TSC is suspected when a person has at least 1 major feature and 1 minor feature of TSC. The features are very specific, and a careful evaluation by a doctor familiar with TSC is necessary to make the diagnosis.

Major Features:

  • More than 2 angiofibromas, which are skin-colored growths of blood vessels in the skin or a thick (fibrous) patch of skin on the forehead

  • 2 or more periungual fibromas or hard growths, around or under the fingernails or toenails

  • More than 3 light-colored areas on the skin, known as hypomelanotic macules or ash leaf spots

  • Shagreen patch, meaning a rough growth of tissue on the surface of the skin

  • Tubers, or thickened areas, found in the brain

  • Nodules (round growths) found in the brain

  • Subependymal giant cell astrocytoma (SEGA), a type of brain cancer

  • Cardiac rhabdomyoma, which is a benign (noncancerous) heart growth

  • Angiomyolipoma of the kidney, which are benign growths that can cause serious medical problems; there is a low risk that these tumors could become cancerous

  • Lymphangiomyomatosis, which are multiple cysts or fluid-filled growths along the lymphatic system under the skin

  • Multiple hemangioblastomas, which are growths of newly formed blood vessels, of the brain, spinal cord, or eye

  • One or more hemangioblastomas in addition to kidney cysts, pancreatic cysts, pheochromocytoma, which is a rare growth in the cells of one of the adrenal glands, or kidney cancer

Minor Features:

  • Multiple pits or dents in the teeth

  • Fibromas (growths) of the gums inside the mouth

  • Multiple kidney cysts

  • Skin discolorations, called “confetti”

  • Changes in the retina inside the eye

  • Hamartomas, which are benign tissue growths

If a person has a family history of TSC, they are also suspected of having TSC if they have any features of the condition. Genetic testing for mutations in the TSC1 and TSC2 genes is available for people and families suspected to have TSC. However, as many as 30% of people with TSC will not have a mutation detected in either of these genes.

What are the estimated cancer risks associated with TSC?

Both kidney cancer and brain cancer have been seen in people with TSC. The risk of kidney cancer is estimated to be about 4%. The risk of the brain cancer SEGA is estimated to be up to 14%. A medication called everolimus (Afinitor) has been approved by the U.S. Food and Drug Administration to treat people with giant cell astrocytoma and other features associated with TSC. This treatment is a pill taken by mouth, which targets an important protein called mTOR for TSC. Talk with your doctor for more information about your personal treatment options.

What are the screening options for TSC?

Suggested screenings for people with TSC or at risk for TSC include:

  • Ultrasound of the kidneys every 1 to 3 years or more frequently if recommended by your health care provider. An ultrasound is a noninvasive test that uses sound waves to create a picture of the internal organs.

  • Magnetic resonance imaging (MRI) or computed tomography (CT or CAT) scans of the kidneys, following an ultrasound evaluation. An MRI uses magnetic fields, not x-rays, to produce detailed images of the body. A CT scan creates a 3-dimensional picture of the inside of the body with an x-ray machine.

  • MRI or CT scan of the head every 1 to 3 years, usually until the teenage years.

  • Electroencephalogram (EEG), for monitoring seizures. An EEG is a test in which electrodes are attached to the scalp, to measure electrical activity of the brain.

  • Developmental and behavioral evaluations of children before they begin school and repeated as necessary

  • Echocardiogram (heart evaluation), if symptoms suggest a need.

  • Chest CT scan, if symptoms suggest a need.

Screening recommendations may change over time as new technologies are developed and more is learned about TSC. It is important to talk with your doctor about appropriate screening tests.

Learn more about what to expect when having common tests, procedures, and scans.

Questions to ask the health care team

If you are concerned about your risk of cancer, talk with your health care team. It can be helpful to bring someone along to your appointments to take notes. Consider asking your health care team the following questions:

  • What is my risk of brain cancer?

  • What is my risk of kidney cancer?

  • What can I do to reduce my risk of cancer?

  • What are my options for cancer screening?

  • What can I do about skin changes?

If you are concerned about your family history and think you or other family members may have TSC, consider asking the following questions:

  • Does my family history increase my risk of brain cancer or kidney cancer?

  • Should I have a cancer risk assessment? What about other members of my family?

  • Will you refer me or my family members to a genetic counselor or other genetics specialist?

  • Should my family or I consider genetic testing?

Related Resources

The Genetics of Cancer

Genetic Testing

What to Expect When You Meet with a Genetic Counselor

Collecting Your Family Cancer History

Sharing Genetic Test Results with Your Family

Family Genetic Testing Q&A

More Information

Tuberous Sclerosis Alliance

National Organization of Rare Disorders

To find a genetic counselor in your area, ask your health care team or visit this website:

National Society of Genetic Counselors