National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is characterized by the growth of benign tumors throughout the body, including in the heart, brain, and kidneys. Certain symptoms develop before to birth, such as heart tumors (rhabdomyoma). Other symptoms become more obvious in childhood, such as developmental delay and skin changes. Lung and kidney tumors are more likely to develop in adulthood. TSC is caused by the TSC1 or TSC2 gene not working correctly. It is inherited in an autosomal dominant pattern. This condition is diagnosed based on a clinical exam, medical tests such as imaging studies, and genetic testing. Treatment is based on managing the symptoms, and includes medications and surgery.[1][2][3][4]
Last updated: 5/20/2020
The following list includes the most common signs and symptoms in people with tuberous sclerosis complex (TSC). These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.[1][5]

Signs and symptoms include:

Skin findings:
  • Small bumps made up of blood vessels (angiofibromas)
  • Patches of thickened, rough skin (shagreen patches)
  • Growths under the fingernails and toenails (ungual fibromas)
  • Light colored skin patches (hypomelanonic macules)
Brain findings:
  • Benign brain tumor (astrocytoma)
  • Abnormal organization of the brain (cortical dysplasia)
  • Nodules in the brain (subependymal nodules)
  • Seizures
Other systems:
  • Benign growth in the retina (retinal hamartoma)
  • Heart muscle tumor (cardiac rhabdomyoma)
  • Formation of unusual clumps of cells in the lungs (pulmonary lymphangiomyomatosis)
  • Kidney growths (renal angiomyolipoma)
  • Developmental delay
  • Intellectual disability
  • Behavioral issues
Symptoms of tuberous sclerosis complex begin before birth and might be noted on ultrasound, such as tumors in the brain and heart (subependymal nodules and cardiac rhabdomyomas). Seizures, intellectual disability, and developmental delay usually appear in childhood. Other symptoms that might develop in childhood include skin changes and kidney symptoms caused by tumors. Brain tumors usually grow during childhood and in teen years, which may lead to other concerns, such as hydrocephalus. In adulthood, kidney and pulmonary symptoms become more common.[3][6]
Last updated: 5/20/2020

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Cortical dysplasia 0002539
Cortical tubers 0009717
Generalized abnormality of skin
Generalised abnormality of skin
0011354
Hypomelanotic macule 0009719
Subependymal nodules 0009716
30%-79% of people have these symptoms
Abnormal social behavior
Abnormal social behaviour
0012433
Aggressive behavior
Aggression
Aggressive behaviour
Aggressiveness
[ more ] 		0000718
Angiofibromas 0010615
Autism 0000717
Cardiac rhabdomyoma 0009729
Chorioretinal hypopigmentation 0040030
Confetti-like hypopigmented macules 0007449
Depressivity
Depression
0000716
Focal-onset seizure
Seizure affecting one half of brain
0007359
Impulsivity
Impulsive
0100710
Infantile spasms 0012469
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Neurodevelopmental delay 0012758
Pulmonary lymphangiomyomatosis 0012798
Repetitive compulsive behavior 0008762
Self-injurious behavior
Self-injurious behaviour
0100716
Shagreen patch 0009721
Skin plaque 0200035
Sleep disturbance
Difficulty sleeping
Trouble sleeping
[ more ] 		0002360
Specific learning disability 0001328
Status epilepticus
Repeated seizures without recovery between them
0002133
5%-29% of people have these symptoms
Anxiety
Excessive, persistent worry and fear
0000739
Attention deficit hyperactivity disorder
Attention deficit
Attention deficit disorder
Attention deficit-hyperactivity disorder
Attention deficits
Childhood attention deficit/hyperactivity disorder
[ more ] 		0007018
Epidermoid cyst
Skin cyst
0200040
Hemoptysis
Coughing up blood
0002105
Hepatic cysts
Liver cysts
0001407
Hypertension 0000822
Noncommunicating hydrocephalus 0010953
Poor speech 0002465
Renal angiomyolipoma 0006772
Respiratory distress
Breathing difficulties
Difficulty breathing
[ more ] 		0002098
Respiratory tract infection
Respiratory infection
0011947
Subependymal giant-cell astrocytoma 0009718
Ungual fibroma 0100804
1%-4% of people have these symptoms
Aortic aneurysm
Bulge in wall of large artery that carries blood away from heart
0004942
Carcinoid tumor 0100570
Internal hemorrhage
Internal bleeding
0011029
Pancreatic endocrine tumor 0030405
Parathyroid adenoma 0002897
Parathyroid hyperplasia
Enlarged parathyroid glands
0008208
Pheochromocytoma 0002666
Pituitary adenoma
Noncancerous tumor in pituitary gland
0002893
Polycystic kidney dysplasia 0000113
Renal cell carcinoma
Cancer starting in small tubes in kidneys
0005584
Respiratory failure 0002878
Retinal astrocytic hamartoma 0012778
Stage 5 chronic kidney disease 0003774
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Last updated: 7/1/2020
Tuberous sclerosis complex (TSC) is caused by the TSC1 or TSC2 gene not working correctly.[5]  DNA changes known as pathogenic variants are responsible for making genes work incorrectly or not at all. 
Last updated: 5/21/2020
Tuberous sclerosis complex (TSC) is inherited in an autosomal dominant pattern. All individuals inherit two copies of each gene.[5] Autosomal means the gene is found on one of the numbered chromosomes found in both sexes. Dominant means that only one altered copy of a gene is necessary to have the condition. The alteration can be inherited from either parent. Sometimes an autosomal dominant condition occurs because of a new genetic alteration (de novo) and there is no history of this condition in the family.
  
Each child of an individual with an autosomal dominant condition has a 50% or 1 in 2 chance of inheriting the alteration and the condition. Typically, children who inherit a dominant alteration will have the condition, but they may be more or less severely affected than their parent. Sometimes a person may have a gene alteration for an autosomal dominant condition and show no signs or symptoms of the condition.  
Last updated: 5/21/2020
A diagnosis of tuberous sclerosis complex is made based on a clinical exam and identification of specific symptoms. Diagnostic criteria have been published for this condition. Genetic testing can confirm the diagnosis.[1]


Last updated: 5/21/2020

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
The treatment for tuberous sclerosis complex is based on managing the symptoms in each person. A type of medication can be helpful in slowing or stopping the growth of some of the associated tumors; including renal angiomyolipomas, subependymal giant cell astrocytomas, lymphangioleiomyomatosis, and facial angiofibromas. In some cases, surgery may be needed.[2][6]

Specialists who may be involved in the care of someone with tuberous sclerosis complex include:
  • Cardiologist
  • Dermatologist
  • Nephrologist
  • Neurologist
  • Ophthalmologist
  • Pulmonologist
  • Urologist
  • Medical geneticist
  • Dentist
Last updated: 5/21/2020

Management Guidelines

  • Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.  

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

  • Everolimus (Brand name: Afinitor) - Manufactured by Novartis Pharmaceuticals Corporation
    FDA-approved indication: April 2018 approved for the adjunctive treatment of adult and pediatric patients age 2 years and older with tuberous sclerosis complex (TSC)-associated partial-onset seizures. April 2012 approved for the treatment of adults with renal angiomyolipoma and tuberous sclerosis complex (TSC) not requiring immediate surgery. October 2010 approved for the treatment of patients with subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis who require therapeutic intervention but are not candidates for curative surgical resection.
    National Library of Medicine Drug Information Portal
    Medline Plus Health Information
  • Vigabatrin (Brand name: Sabril) - Manufactured by Lundbeck
    FDA-approved indication: For infantile spasms (IS) 1 month to 2 years of age
    National Library of Medicine Drug Information Portal
    Medline Plus Health Information
The exact number of people with tuberous sclerosis complex is unknown.  It has been estimated that about 40,000 people in the United States have tuberous sclerosis complex.[7]
Last updated: 5/21/2020

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
The differential diagnosis includes vitiligo, Ito hypomelanosis, cardiac myxoma, isolated brain tumors, pulmonary emphysema, acne, skin rash.
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Tuberous sclerosis complex. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Patient Registry

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources

  • Patient Access Network Foundation (PAN Foundation) has Assistance Programs for those with health insurance who reside in the United States. The disease fund status can change over time, so you may need to check back if funds are not currently available. 

Education Resources

  • The Genetics Education Materials for School Success (GEMSS) aims to assure that all children with genetic health conditions succeed in school-life. Their Web site offers general and condition-specific education resources to help teachers and parents better understand the needs of students who have genetic conditions.

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Tuberous sclerosis complex. This website is maintained by the National Library of Medicine.
  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
  • The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Tuberous sclerosis complex. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • Can tuberous sclerosis affect blinking and eye closure? If not, what could cause this? See answer


  1. Northrup H, Krueger DA. International Tuberous Sclerosis Complex Consensus Group. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013; 49(4):243-254. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4080684/.
  2. Krueger DA, Northrup H. International Tuberous Sclerosis Complex Consensus Group. Tuberous sclerosis complex surveillance and management: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013; 49(4):255-265. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4058297/.
  3. Peron A, Canevini MP, Ghelma F, Di Marco F, Vignoli A. Healthcare transition from childhood to adulthood in Tuberous Sclerosis Complex. Am J Med Genet C Semin Med Genet. 2018; 178(3):355-364. https://pubmed.ncbi.nlm.nih.gov/30253036.
  4. Caban C, Khan N, Hasbani DM, Crino PB. Genetics of tuberous sclerosis complex: implications for clinical practice.. Appl Clin Genet. 2016; 10:1-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5189696/.
  5. Northrup H, Koenig MK, Pearson DA, Au K-S. Tuberous Sclerosis Complex. GeneReviews. Updated Apr 16, 2020; https://www.ncbi.nlm.nih.gov/books/NBK1220/.
  6. De Waele L, Lagae L, Mekahli D. Tuberous sclerosis complex: the past and the future. Pediatr Nephrol. Oct 2015; 30(10):1771-80. https://www.ncbi.nlm.nih.gov/pubmed/25533384.
  7. Hyman MH, Whittemore VH. National Institutes of Health consensus conference: tuberous sclerosis complex. Arch Neurol. May 2000; 57(5):662-5. https://www.ncbi.nlm.nih.gov/pubmed/10815131.