Information on DNA Testing
Tuberous sclerosis complex (TSC) is a genetic condition, meaning that it is caused by a change, or mutation, in one gene. Genes are the instructions for the normal growth and maintenance of our bodies. Each of us has thousands of genes, and each gene is responsible for the direction of a specific protein or component of our bodies. A gene that carries a mutation is unable to instruct the body to grow correctly, causing a disruption in normal development and functioning.
Mutations in one of two genes, TSC1 and TSC2, have been identified as causes for tuberous sclerosis.
All genes, including those involved in TSC, come in pairs, with one copy inherited from (or passed down by) the mother, and the other copy inherited from the father. In some genetic conditions, like TSC, a mutation in one copy of the gene is enough to cause the condition. These conditions are called dominant conditions because the mutation in one copy "dominates" over the normal copy, causing the condition and its symptoms. In other genetic conditions, both copies of the gene must have mutations before the symptoms occur. These are known as recessive conditions. One well-known recessive condition is cystic fibrosis.
Approximately 33 percent, or one-third, of people with TSC inherit it from a parent who also has tuberous sclerosis. This occurs via dominant inheritance. When you have children, you pass on one copy of each of your gene pairs to the child, and your partner passes on one copy. The passage of one gene copy from each parent ensures that the child is a genetic "mix" of both parents. If a parent has TSC and passes on the copy of the gene with the mutation, then the child will also have TSC. If the parent passes on the copy of the gene without the mutation, the child will not have TSC. Thus, there is a 50 percent chance with each pregnancy for a parent with TSC to have a child with TSC. This is true regardless of the sex of the parent or the sex of the child.
In the remaining 66 percent, or two-thirds, of people with TSC, neither parent shows any symptoms or signs of TSC. It appears that one of the normal genes from either parent changes to the abnormal form, leading to a new (or sporadic) occurrence of TSC in the child. Normally, these parents do not have another child with TSC because the mutation was sporadic, not inherited. However, some families have more than one child with tuberous sclerosis, even though neither parent showed symptoms or findings of TSC.
How does this occur? Scientists have determined that a small number of physically unaffected parents of a child with TSC actually have TSC mutations in some of their cells. Because the mutation is limited to a small portion of all of the body's cells, these individuals show no signs of TSC. But if a portion of the egg or sperm cells of a parent carries the TSC mutation, that parent can have more than one affected child, possibly at the same 50/50 chance that people with TSC have. A person who carries cells with TSC mutations in her egg or his sperm supply has germline mosaicism.
"Mosaicism" means that the person's body is made up of a combination of cells with and cells without a TSC mutation. "Germline" refers to the presence of cells with TSC mutations in the egg or sperm cell supply. Germline mosaicism is relatively rare, and this explanation does not apply to most families with a sporadically affected child. However, the occurrence of germline mosaicism has led geneticists to estimate a recurrence risk (or chance that a family with a sporadically affected child will have another child with TSC) ranging from 1 percent to 3 percent. At this time, there is no simple way to determine whether an unaffected parent of a child with TSC has germline mosaicism.