Is Li-Fraumeni syndrome inherited ?

[Anonymous]

Is Li-Fraumeni syndrome inherited, and what is the chance my children and other relatives have it?

[Genetic Counselor]

Li-Fraumeni syndrome follows what is called autosomal dominant inheritance.

We all carry two copies of each gene, one from each parent. A single faulty copy of TP53 is enough to cause the condition. When a parent has Li-Fraumeni syndrome, each child has a 1-in-2 chance of inheriting the faulty copy and a 1-in-2 chance of inheriting the working copy. It is like tossing a coin for each pregnancy. The chance is the same for every child, and for sons and daughters alike. It does not skip a generation, although a family history can look “quiet” if relatives died young from other causes, the family is small, or the gene change caused milder disease in earlier generations.

Most people with Li-Fraumeni syndrome inherited it from a parent. However, in about 7–20% of people, the change is new and started with them. This is called a de novo change. In that situation, the parents usually do not carry it, and the chance for brothers and sisters is low. Brothers and sisters are still offered testing because a parent can rarely carry the change in only some cells, including egg or sperm cells, without it showing up in a blood test.

Once the family’s TP53 change is known, testing relatives becomes simple and accurate. This step-by-step testing of relatives is called cascade testing:
–Parents, brothers, sisters, and children first
–Wider family next

Because some Li-Fraumeni cancers occur in infancy and early childhood, and screening begins from birth, guidelines support testing at birth (using cord blood) or soon after. Include older children and teenagers in the discussion and ask for their agreement.
A relative who tests negative for the known family change does not have Li-Fraumeni syndrome and cannot pass it on. Their cancer risk is generally similar to that of the general population. If the family change has not been found, a negative test in a relative cannot rule out the condition, and screening decisions need a genetics team’s guidance.

[Author]

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