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Disease Profile

Tuberous sclerosis complex

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-5 / 10 000

33,100 - 165,500

US Estimated

1-5 / 10 000

51,350 - 256,750

Europe Estimated

Age of onset

All ages

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ICD-10

Q85.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Tuberous sclerosis; Bourneville syndrome

Categories

Blood Diseases; Congenital and Genetic Diseases; Eye diseases;

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]

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]

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.

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

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.

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]

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

    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

    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

      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

        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.

            References

            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.

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