TSC2 gene

Associated Syndrome Name: Tuberous Sclerosis Complex (TSC)

TSC2 Summary Cancer Risk Table

Cancer Genetic Cancer Risk
OtherHigh Risk
RenalElevated Risk

TSC2 gene Overview

Tuberous Sclerosis Complex (TSC) 1, 2, 3, 4, 5, 6, 7
  • Individuals with TSC2 mutations have Tuberous Sclerosis Complex (TSC).
  • Patients with TSC have an elevated risk for renal cancer, which may be diagnosed at young ages. A high percentage of children with TSC will have some sort of kidney disease due to benign tumors or cysts.
  • Patients with TSC often have a wide variety of other, non-malignant features associated with this condition, many of which require medical attention. Benign tumors can occur throughout the body (i.e., angiomyolipoma), including in the skin, brain, kidneys, lungs, and heart. Individuals with TSC frequently have epilepsy and can also be affected by neuropsychiatric conditions such as developmental delay and autism spectrum disorders.
  • Although there are increased risks for cancer and a high risk for other medical problems in patients with TSC, these risks can be managed with appropriate medical care. Guidelines from the National Comprehensive Cancer Network (NCCN) and the International Tuberous Sclerosis Complex Consensus Group are listed below. Since TSC is a complex condition, patients with TSC2 mutations and a diagnosis of TSC should be managed by a multidisciplinary team with expertise in medical genetics and the prevention and treatment of the complications associated with this condition.

TSC2 gene Cancer Risk Table

Cancer Type Age Range Cancer Risk Risk for General Population
RenalTo age 801, 4, 7, 82%-5%1.4%
Malignant AngiomyolipomaTo age 804, 5, 8Rare, but elevated risk<0.1%
Other - Non-malignant features of TSCAll ages2, 3, 4, 5, 6TSC is associated with many life-threatening non-malignant clinical features, some of which may require medical intervention as early as infancy (see Overview).NA

TSC2 Cancer Risk Management Table

The overview of medical management options provided is a summary of professional society guidelines. The most recent version of each guideline should be consulted for more detailed and up-to-date information before developing a treatment plan for a particular patient.

This overview is provided for informational purposes only and does not constitute a recommendation. While the medical society guidelines summarized herein provide important and useful information, medical management decisions for any particular patient should be made in consultation between that patient and his or her healthcare provider and may differ from society guidelines based on a complete understanding of the patient’s personal medical history, surgeries and other treatments.

Cancer Type Procedure Age to Begin Frequency
(Unless otherwise indicated by findings)
RenalAbdominal imaging with MRI (preferred) or CT, with and without contrast612 yearsEvery 3 to 5 years
Malignant AngiomyolipomaAbdominal MRI2, 4At time of diagnosis of TSCEvery 1 to 3 years
Consider everolimus therapy for asymptomatic, growing angiomyolipoma measuring >3 cm in diameter.4, 6IndividualizedNA
Other - Non-malignant features of TSCMultiple screenings recommended, which may include comprehensive physical exam, brain MRI, echocardiogram, chest CT, and evaluations for neuropsychiatric disorders.2, 4At time of diagnosis of TSCVaries

Information for Family Members

The following information for Family Members will appear as part of the MMT for a patient found to have a mutation in the TSC2 gene.

This patient's relatives are at risk for carrying the same mutation(s) and associated cancer risks as this patient. Cancer risks for females and males who have this/these mutation(s) are provided below.

Family members should talk to a healthcare provider about genetic testing. Close relatives such as parents, children, brothers and sisters have the highest chance of having the same mutation(s) as this patient. Other more distant relatives such as cousins, aunts, uncles, and grandparents also have a chance of carrying the same mutation(s). Testing of at-risk relatives can identify those family members with the same mutation(s) who may benefit from surveillance and early intervention.

Approximately two-thirds of individuals with TSC have not inherited the TSC2 mutation from a parent. In these cases the mutation has developed spontaneously in that individual (a de novo mutation). Once this occurs, the children of that individual are each at 50% risk of inheriting the mutation.2, 3, 4, 5

Since TSC2 mutations carry a risk for complications in children and some screenings are recommended to begin in infancy, mutation testing should occur as soon as a diagnosis of TSC is suspected.2, 3, 4, 5

References

  1. Cook JA, et al. A cross sectional study of renal involvement in tuberous sclerosis. J Med Genet. 1996 33:480-4. PMID: 8782048.
  2. Krueger DA, et al. Tuberous sclerosis complex surveillance and management: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013 49:255-65. PMID: 24053983.
  3. Northrup H, et al. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013. 49:243-54. PMID: 24053982.
  4. Northrup H,et al. Tuberous Sclerosis Complex. 2020 Apr 16 In: Adam MP, et al., editors. GeneReviews® [Internet]. PMID: 20301399.
  5. Nair N, et al. Renal Manifestations of Tuberous Sclerosis Complex. J Kidney Cancer VHL. 2020 7:55-19. PMID: 32953421.
  6. Motzer RJ et al. NCCN Clinical Practice Guidelines in Oncology®: Kidney Cancer. V 1.2022. July 1. Available at https://www.nccn.org.
  7. Stillwell TJ, et al. Renal lesions in tuberous sclerosis. J Urol. 1987 138:477-81. PMID: 3625844.
  8. SEER*Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute. [Cited 2020 Sep 14]. Available from https://seer.cancer.gov/explorer/.
Last Updated on 29-Sep-2022