Li–Fraumeni syndrome
The Li -Fraumeni syndrome is an autosomal dominant hereditary disease associated with multiple tumors, which often occur in early life. The disease is very rare.
Pathogenesis
The syndrome is often a germline mutation in a tumor suppressor, the gene coding for the p53 protein TP53 gene ( chromosome 17 locus P13.1 ). The risk in the age of 30 from cancer is 50 % and is thus compared to the total population (1%) significantly increased. As with the Li -Fraumeni syndrome tumors are socialized soft tissue sarcomas, breast cancer, bone sarcomas, leukemias, astrocytomas, Plexuskarzinome and carcinoma of the adrenal cortex. In affected families also have an increased incidence of lung cancer, tumors of the stomach and intestine, ovarian cancer and lymphoma was detected. Since about 30 % of patients no mutation of the TP53 gene can be detected, undetected defects of the p53 signal transduction pathway are discussed as additional triggers so far. Diseases that are associated with mutations of the CHEK2 gene has been referred to as Li -Fraumeni syndrome 2. Another locus was recently identified on chromosome 1.
Diagnosis
Since only about 70% of patients have a detectable mutation of the TP53 gene, the diagnosis is made based on the clinical appearance. The following criteria must be met in order to diagnose a Li -Fraumeni syndrome:
- Patient with sarcoma before the age of 45 plus
- At least one first-degree relative before the age of 45 fell ill from cancer or ill in the course of his life on a sarcoma
- At least one second-degree relative before the age of 45 fell ill from cancer or ill in the course of his life on a sarcoma
In addition to the Li -Fraumeni syndrome in a narrow sense, a Li-Fraumeni like syndrome (Li- Fraumeni like syndrome ) has been defined, but in which a p53 mutation is much less detectable. This is clinically defined as follows:
- Patient with infantile tumor, sarcoma, brain tumor, or adrenal tumor before the age of 45 plus
- A first-or second-degree suffering from a socialized with Li -Fraumeni syndrome tumor at any age plus
- Another first-or second-degree ill with any tumor before reaching the age of 60.
Li -Fraumeni syndrome is diagnosed by following two criteria:
- Three independent primary tumors in a person, 45 years before the
- A tumor in childhood
- A tumor of the Li -Fraumeni tumor spectrum before the age of 45
- A first- or second-degree relative with a tumor of the LF spectrum of tumors and another relative with any tumor before age 60
Therapeutic approaches
In order to detect newly emerging tumors as early as possible, close-knit investigations are required. One therapeutic approach could be the introduction of healthy p53 DNA in the tumor cells. This adenoviruses are used to insert the genetic material into the tumor cells. After successful individual therapy trials the drug Advexin is a European subsidiary of the manufacturer Introgen for patients with Li -Fraumeni syndrome on a compassionate use basis.