Tuberous sclerosis complex

Información en español Title

Other Names:

Tuberous sclerosis; Bourneville syndrome

Categories:

Blood Diseases; Congenital and Genetic Diseases; Eye diseases; Blood Diseases; Congenital and Genetic Diseases; Eye diseases; Kidney and Urinary Diseases; Nervous System Diseases; Rare Cancers; Skin Diseases See More

Summary Summary

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

Symptoms Symptoms

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

Showing of 52 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 12/1/2020

Cause Cause

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

Inheritance Inheritance

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

Diagnosis Diagnosis

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.

Treatment Treatment

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

Statistics Statistics

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

Do you have updated information on this disease? We want to hear from you.

Find a Specialist Find a Specialist

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

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Related Diseases Related Diseases

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 Research

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

The Developmental Synaptopathies Associated with TSC, PTEN and SHANK3 Mutations Consortium is an integrated group of academic medical centers, patient support organizations, and clinical research resources dedicated to conducting clinical research on Tuberous Sclerosis Complex (TSC1 and TSC2 genes), PTEN ASD/ID syndrome and Phelan-McDermid syndrome (PMS; SHANK3 gene). The Consortium has a contact registry for patients who wish to be contacted about clinical research opportunities and updates on the progress of the research projects.

For more information on the registry see: https://www.rarediseasesnetwork.org/registry/index.htm

Organizations Organizations

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

Tuberous Sclerosis Alliance (TS Alliance)
801 Roeder RD, Suite 750
Silver Spring, MD 20910-4487
Toll-free: 1-800-225-6872
Telephone: +1-301-562-9890
Fax: +1-301-562-9870
E-mail: info@tsalliance.org
Website: https://www.tsalliance.org/
For immediate support or information, please email Dena Hook at dhook@tsalliance.org.

Do you know of an organization? We want to hear from you.

Living With Living With

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.

Learn More Learn More

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

MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
MedlinePlus Genetics contains information on Tuberous sclerosis complex. This website is maintained by the National Library of Medicine.
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.

News & Events News & Events

News

NORD RareLaunch® Workshops
December 1, 2020
Rare Diseases Are Not Rare - Gallery of Creative Work Raises Awareness of Rare Diseases
September 1, 2020
NIH-Supported Research Survey to Examine Impact of COVID-19 on Rare Diseases Community
May 22, 2020
NCATS Translational Approach Addresses COVID-19
May 21, 2020

GARD Answers GARD Answers

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

Have a question? Contact a GARD Information Specialist.

References References

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/.
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/.
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.
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/.
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/.
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.
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.