Tuberous sclerosis

Inheritance

How is tuberous sclerosis inherited?

Tuberous sclerosis is inherited in autosomal dominant manner. This is one way a disorder or trait can be passed down through a family. The first word, "autosomal," means the altered gene is on a chromosome that both males and females carry. Therefore, tuberous sclerosis can affect either gender. The second word, "dominant," means a gene change in one copy of a person's TSC1 or TSC2 gene is enough for them to develop the disease.

Humans have two copies of every gene - one from our mother and one from our father. In a dominant condition, only gene copy of them needs to have a disease-causing change to lead to the condition. This means that if a parent carries a changed TSC1 or TSC2 gene, they have a 50% chance to pass the affected gene to each of their offspring, regardless of gender. This also means that there is a 50% chance that an affected parent would not pass this on to their children.

In some people, there is no previous history of tuberous sclerosis in the family. The altered TSC1 or TSC2 gene occurs randomly. This is also called a de novo mutation. The altered gene in the child can be passed on as an autosomal dominant trait. In most families with a child with a de novo mutation, the likelihood of having another child with tuberous is extremely low. One estimate states that 80% of people with tuberous sclerosis have a de novo mutation. A mutation in the TSC2 gene is about four times more common than a mutation in the TSC1 gene.

Individuals who have a family member with tuberous sclerosis and wish to learn more about the genetics of the condition can meet with a genetic counselor to discuss testing options.

References
  • Owens J, Bodensteiner JB. Tuberous sclerosis complex: genetics, clinical features and diagnosis. UpToDate Inc. website. Accessed May 24, 2017. www.uptodate.com/contents/tuberous-sclerosis-complex-genetics-clinical-features-and-diagnosis
  • Tuberous Sclerosis. The National Organization for Rare Disorders website. Accessed June 8, 2017. https://rarediseases.org/rare-diseases/tuberous-sclerosis/
  • Tuberous Sclerosis Complex. Genetics Home Reference website. Accessed June 8, 2017. https://ghr.nlm.nih.gov/condition/tuberous-sclerosis-complex
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More Inheritance Content

How likely is tuberous sclerosis to be passed on in a family?

What does it mean to have inherited a "variant" or "variant of unknown significance" in the gene for tuberous sclerosis?

My child has tuberous sclerosis. Will others in the family have it?

How likely is tuberous sclerosis to be passed on in a family?

Humans inherit two copies of most of genes from their parents. One copy comes from the mother and the other copy comes from the father. In tuberous sclerosis, only one parent must pass along a nonworking copy of the TSC1 or TSC2 gene for the disorder to develop. Because of this, tuberous sclerosis is inherited in what is called an autosomal dominant pattern. This means a person only needs only one altered gene to have the disorder. If one parent has an altered TSC1 or TSC2 gene, which causes their disease, then each of their children will have a 50% chance of inheriting that mutation and developing tuberous sclerosis.

In some families, a child will develop tuberous sclerosis and be the first person in the family with the disorder. This occurs because of a de novo mutation, which means that the altered gene occurs randomly. The child who carries the altered gene can pass on the alteration in an autosomal dominant manner. In most families with a child with a de novo mutation, the likelihood of having another child with tuberous sclerosis is extremely low.

References
  • Owens J, Bodensteiner JB. Tuberous sclerosis complex: genetics, clinical features and diagnosis. UpToDate Inc. website. Accessed May 24, 2017. www.uptodate.com/contents/tuberous-sclerosis-complex-genetics-clinical-features-and-diagnosis
  • Northrup H, Koenig MK, Pearson DA, et al. Tuberous Sclerosis Complex. 1999 Jul 13 [Updated 2018 Jul 12]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1220 Accessed 11JAN2020.
What does it mean to have inherited a "variant" or "variant of unknown significance" in the gene for tuberous sclerosis?

Tuberous sclerosis is caused by a change (mutation) in one of two genes: TSC1 or TSC2 . Not all changes in a gene necessarily cause disease. If a change is known to result in tuberous sclerosis, it is known as a pathogenic or disease-causing variant. More than 500 different changes (mutations) in these two genes have been identified as disease-causing in tuberous sclerosis. Sometimes gene changes are found and scientists are unsure what it means, either because it has not been found before or has only been found in a few people. This is known as a variant of unknown significance. If you have a variant of unknown significance in the TSC1 or TSC2 genes, talk to your doctor about further testing that may help find out whether the gene change is pathogenic or not. A genetic counselor may also be able to help you review your test results. To find a genetic counselor near you who can discuss testing and results, visit the National Society of Genetic Counselors Find a Genetic Counselor website.

References
  • Northrup H, Koenig MK, Pearson DA, et al. Tuberous Sclerosis Complex. 1999 Jul 13 [Updated 2018 Jul 12]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1220 Accessed 11JAN2020.
  • DiMario FJ Jr, Sahin M, Ebrahimi-Fakhari D. Tuberous sclerosis complex. Pediatr Clin North Am. 2015 ;62(3):633-48. https://www.ncbi.nlm.nih.gov/pubmed/26022167
My child has tuberous sclerosis. Will others in the family have it?

Tuberous sclerosis is inherited in an autosomal dominant inheritance pattern which means that every first degree relative of an affected individual has a 50% chance of also having the condition. First degree relatives are siblings, children, and parents. Second degree relatives should have testing after first degree relatives are all tested.

In a specific example, let's say 27-year-old Andrea has been diagnosed with tuberous sclerosis. Andrea has 3 children. EACH of her children has an individual 50% chance to also have it. Andrea has 2 siblings: one brother and one sister. EACH of her siblings has an individual 50% chance to also have it. Andrea's mother has testing and is negative. This means that Andrea's mothers side of the family does NOT need to have any more testing. Andrea's father has testing and is positive. Each of Andrea's father's siblings should have testing as well, because they have an individual 50% chance of being positive as well. A genetic counselor can help individuals with TS understand the impact on family members and review testing options. To find a genetic counselor near you who can discuss testing and results, visit the National Society of Genetic Counselors Find a Genetic Counselor website.

References

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