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Genetics Home Reference: your guide to understanding genetic conditions
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Tuberous sclerosis complex

Reviewed June 2009

What is tuberous sclerosis complex?

Tuberous sclerosis complex is a genetic disorder characterized by the growth of numerous noncancerous (benign) tumors in many parts of the body. These tumors can occur in the skin, brain, kidneys, and other organs, in some cases leading to significant health problems. Tuberous sclerosis complex also causes developmental problems, and the signs and symptoms of the condition vary from person to person.

Virtually all affected people have skin abnormalities, including patches of unusually light-colored skin, areas of raised and thickened skin, and growths under the nails. Tumors on the face called facial angiofibromas are also common beginning in childhood.

Tuberous sclerosis complex often affects the brain, causing seizures, behavioral problems such as hyperactivity and aggression, and intellectual disability or learning problems. Some affected children have the characteristic features of autism, a developmental disorder that affects communication and social interaction. Benign brain tumors can also develop in people with tuberous sclerosis complex; these tumors can cause serious or life-threatening complications.

Kidney tumors are common in people with tuberous sclerosis complex; these growths can cause severe problems with kidney function and may be life-threatening in some cases. Additionally, tumors can develop in the heart, lungs, and the light-sensitive tissue at the back of the eye (the retina).

How common is tuberous sclerosis complex?

Tuberous sclerosis complex affects about 1 in 6,000 people.

What genes are related to tuberous sclerosis complex?

Mutations in the TSC1 or TSC2 gene can cause tuberous sclerosis complex. The TSC1 and TSC2 genes provide instructions for making the proteins hamartin and tuberin, respectively. Within cells, these two proteins likely work together to help regulate cell growth and size. The proteins act as tumor suppressors, which normally prevent cells from growing and dividing too fast or in an uncontrolled way.

People with tuberous sclerosis complex are born with one mutated copy of the TSC1 or TSC2 gene in each cell. This mutation prevents the cell from making functional hamartin or tuberin from the altered copy of the gene. However, enough protein is usually produced from the other, normal copy of the gene to regulate cell growth effectively. For some types of tumors to develop, a second mutation involving the other copy of the TSC1 or TSC2 gene must occur in certain cells during a person's lifetime.

When both copies of the TSC1 gene are mutated in a particular cell, that cell cannot produce any functional hamartin; cells with two altered copies of the TSC2 gene are unable to produce any functional tuberin. The loss of these proteins allows the cell to grow and divide in an uncontrolled way to form a tumor. In people with tuberous sclerosis complex, a second TSC1 or TSC2 mutation typically occurs in multiple cells over an affected person's lifetime. The loss of hamartin or tuberin in different types of cells leads to the growth of tumors in many different organs and tissues.

How do people inherit tuberous sclerosis complex?

Tuberous sclerosis complex has an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to increase the risk of developing tumors and other problems with development. In about one-third of cases, an affected person inherits an altered TSC1 or TSC2 gene from a parent who has the disorder. The remaining two-thirds of people with tuberous sclerosis complex are born with new mutations in the TSC1 or TSC2 gene. These cases, which are described as sporadic, occur in people with no history of tuberous sclerosis complex in their family. TSC1 mutations appear to be more common in familial cases of tuberous sclerosis complex, while mutations in the TSC2 gene occur more frequently in sporadic cases.

Where can I find information about treatment for tuberous sclerosis complex?

You may find information on treatment or management of tuberous sclerosis complex or some of its symptoms in the links below, particularly the links for Gene Reviews, MedlinePlus Encyclopedia, Educational resources, and Patient support.

Where can I find additional information about tuberous sclerosis complex?

You may find the following resources about tuberous sclerosis complex helpful. These materials are written for the general public.

  • MedlinePlus - Health information
    • Encyclopedia: Tuberous Sclerosis (http://www.nlm.nih.gov/medlineplus/ency/article/000787.htm)
    • Health Topic: Tuberous Sclerosis (http://www.nlm.nih.gov/medlineplus/tuberoussclerosis.html)
  • Additional NIH Resources - National Institutes of Health
    • National Center for Biotechnology Information: Genes and Disease (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowSection&rid=gnd.section.221)
    • National Institute of Neurological Disorders and Stroke (http://www.ninds.nih.gov/disorders/tuberous_sclerosis/tuberous_sclerosis.htm)
  • Educational resources - Information pages
    • Ask the Geneticist: Genetic testing for tuberous sclerosis (http://genetics.emory.edu/ask/question.php?question_id=2492)
    • Ask the Geneticist: Inheritance of Tuberous Sclerosis (http://genetics.emory.edu/ask/question.php?question_id=1086)
    • California Department of Developmental Services (http://www.ddhealthinfo.org/coursebuilder/?id=41)
    • Children's Hospital Boston (http://www.childrenshospital.org/az/Site604/mainpageS604P0.html)
    • Children's Hospital St. Louis: Tuberous Sclerosis Clinic (http://www.stlouischildrens.org/content/medservices/TuberousSclerosisClinic.htm)
    • Cincinnati Children's Tuberous Sclerosis Program (http://www.cincinnatichildrens.org/svc/alpha/t/tuberous-sclerosis)
    • Madisons Foundation (http://www.madisonsfoundation.org/index.php/component/option,com_mpower/diseaseID,224/)
    • Massachusetts General Hospital (http://www2.massgeneral.org/livingwithtsc/)
    • Merck Manual Home Edition for Patients and Caregivers (http://www.merck.com/mmhe/sec23/ch288666/ch288666e.html)
    • New York Online Access to Health (http://www.noah-health.org/en/bns/disorders/tuberous/)
    • Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=805)
    • Penn State Children's Hospital (http://www.hmc.psu.edu/childrens/healthinfo/t/tuberoussclerosis.htm)
    • Swedish Information Center for Rare Diseases (http://www.socialstyrelsen.se/en/rarediseases/Tuberous+sclerosis.htm)
    • The Children's Hospital (Denver) Tuberous Sclerosis Clinic (http://www.thechildrenshospital.org/conditions/nervous/conditions/tuberous-sclerosis.aspx)
  • Patient support - For patients and families
    • Epilepsy Foundation (http://www.epilepsyfoundation.org/)
    • Genetic Alliance (http://www.geneticalliance.org/ws_display.asp?filter=infosearch_results&info_keyword=Tuberous+Sclerosis&expand=Treatment)
    • National Organization for Rare Disorders (http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Tuberous+Sclerosis)
    • Resource list from the University of Kansas Medical Center (http://www.kumc.edu/gec/support/tuberous.html)
    • The Tuberous Sclerosis Association (UK) (http://www.tuberous-sclerosis.org/)
    • Tuberous Sclerosis Alliance (http://www.tsalliance.org)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=tuberous-sclerosis)
  • Gene Tests - DNA tests ordered by healthcare professionals
    • Gene Test: Tuberous Sclerosis 1 (http://www.genetests.org/query?testid=54046)
    • Gene Test: Tuberous Sclerosis 2 (http://www.genetests.org/query?testid=54049)
  • ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/search/condition=%22tuberous+sclerosis%22)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=(Tuberous+Sclerosis[MAJR])+AND+(tuberous+sclerosis[TI])+AND+review[pt]+AND+english[la]+AND+human[mh]+AND+"last+1800+days"[dp])
  • Online Books - Medical and science texts
    Scriver's Online Metabolic and Molecular Bases of Inherited Disease (OMMBID): Tuberous Sclerosis (http://books.mcgraw-hill.com/getommbid.php?isbn=0071459960&template=ommbid&c=233)
  • OMIM - Genetic disorder catalog (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191100)

What other names do people use for tuberous sclerosis complex?

  • Bourneville Disease
  • Bourneville Phakomatosis
  • cerebral sclerosis
  • Epiloia
  • sclerosis tuberosa
  • tuberose sclerosis

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about tuberous sclerosis complex?

  • See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
  • Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
  • Submit your question to Ask the Geneticist (http://www.askthegen.org/).

What glossary definitions help with understanding tuberous sclerosis complex?

autism ; autosomal ; autosomal dominant ; benign ; carcinoma ; cardiac ; cell ; complication ; familial ; gene ; heterozygosity ; hyperactivity ; inheritance ; kidney ; loss of heterozygosity ; mutation ; new mutation ; pattern of inheritance ; protein ; renal ; retina ; rhabdomyosarcoma ; sclerosis ; seizure ; sign ; sporadic ; symptom ; tissue ; tumor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References
  • Crino PB, Nathanson KL, Henske EP. The tuberous sclerosis complex. N Engl J Med. 2006 Sep 28;355(13):1345-56. Review. No abstract available. (http://www.ncbi.nlm.nih.gov/pubmed/17005952?dopt=Abstract)
  • Curatolo P, Bombardieri R, Jozwiak S. Tuberous sclerosis. Lancet. 2008 Aug 23;372(9639):657-68. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18722871?dopt=Abstract)
  • Gene Review (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=tuberous-sclerosis)
  • Hyman MH, Whittemore VH. National Institutes of Health consensus conference: tuberous sclerosis complex. Arch Neurol. 2000 May;57(5):662-5. Review. No abstract available. (http://www.ncbi.nlm.nih.gov/pubmed/10815131?dopt=Abstract)
  • Lewis JC, Thomas HV, Murphy KC, Sampson JR. Genotype and psychological phenotype in tuberous sclerosis. J Med Genet. 2004 Mar;41(3):203-7. No abstract available. (http://www.ncbi.nlm.nih.gov/pubmed/14985384?dopt=Abstract)
  • Maria BL, Deidrick KM, Roach ES, Gutmann DH. Tuberous sclerosis complex: pathogenesis, diagnosis, strategies, therapies, and future research directions. J Child Neurol. 2004 Sep;19(9):632-42. No abstract available. (http://www.ncbi.nlm.nih.gov/pubmed/15563008?dopt=Abstract)
  • Narayanan V. Tuberous sclerosis complex: genetics to pathogenesis. Pediatr Neurol. 2003 Nov;29(5):404-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14684235?dopt=Abstract)
  • Roach ES, Sparagana SP. Diagnosis of tuberous sclerosis complex. J Child Neurol. 2004 Sep;19(9):643-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15563009?dopt=Abstract)
  • Rosser T, Panigrahy A, McClintock W. The diverse clinical manifestations of tuberous sclerosis complex: a review. Semin Pediatr Neurol. 2006 Mar;13(1):27-36. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16818173?dopt=Abstract)
  • Schwartz RA, Fernández G, Kotulska K, Jóźwiak S. Tuberous sclerosis complex: advances in diagnosis, genetics, and management. J Am Acad Dermatol. 2007 Aug;57(2):189-202. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17637444?dopt=Abstract)
  • Thiele EA. Managing epilepsy in tuberous sclerosis complex. J Child Neurol. 2004 Sep;19(9):680-6. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15563014?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: June 2009
Published: November 20, 2009