Li-Fraumeni syndrome is a hereditary disorder that leads to increased tumor formation at a young age. The resulting tumors are mostly malignant and can affect a wide variety of organs and body regions. The disease occurs very rarely.
What is Li-Fraumeni syndrome?
Experts understand Li-Fraumeni syndrome to be a genetic defect that is inherited in an autosomal dominant manner. In affected individuals, malignant tumors often form in childhood or during puberty. These can affect a wide variety of body regions. However, tumors of the adrenal glands, breast cancer, bone cancer and leukemias are particularly common in connection with Li-Fraumeni syndrome. The cancer risk of a person with Li-Fraumeni syndrome is significantly increased:
While healthy people under 30 statistically have only a 1% risk of developing cancer, the probability with the genetic defect is 50%. The disease occurs very rarely.
Causes
The causes of Li-Fraumeni syndrome lie in a genetic defect. The so-called autosomes (the chromosomes that do not belong to the sex chromosomes) are affected here. In 70% of all cases of Li-Fraumeni syndrome, the defect is a mutation of the TP53 gene, which plays a crucial role in tumor suppression (i.e. preventing tumor growth). As a result, tumor formation is increased. If there is no detectable mutation of the gene, the disease may also result from a disturbance of signal transduction in the context of tumor suppression. Most patients with Li-Fraumeni syndrome come from families in which the disease has already occurred. In contrast, nearly a quarter of affected individuals develop the disease because of a spontaneous gene mutation.
Symptoms, complaints, and signs
Depending on the region of the body in which the tumor is located, Li-Fraumeni syndrome can cause quite different symptoms and complaints. If the adrenal glands are affected, hormone imbalances may occur, including high blood pressure, muscle spasms, external changes, and depression. If blood pressure is involved, palpable metastases form, which can also cause hormonal disturbances. Bone cancer can manifest itself through pain, restricted movement and swelling. Typical of such cartilage sarcoma is also the severe course – more than 50 percent of those affected die within the next five years. Tumors of the central nervous system also have a poor prognosis. They are manifested by paralysis, loss of consciousness, nerve pain and a number of other symptoms and complaints. Leukemia can be seen externally and, as the disease progresses, causes symptoms such as nausea and vomiting, fatigue, and impaired physical and mental performance. Thus, the symptoms of Li-Fraumeni syndrome can affect the entire body and cause a variety of health problems. The tumor usually arises at a young age and develops rapidly. They are mainly malignant tumors that take a severe course and are fatal in many cases.
Diagnosis and course
The presence of Li-Fraumeni syndrome can be determined in many cases (approximately 70%) by a detectable mutation of the TP53 gene. If such a mutation is present, the existence of the disease is virtually established. However, the remaining 30 % of affected individuals do not exhibit any visible gene alteration. Here, the diagnosis is made on the basis of the so-called clinical presentation. Anyone who develops sarcoma before the age of 45 and has at least one first- or second-degree relative who developed cancer or sarcoma in general before the age of 45 is most likely to suffer from Li-Fraumeni syndrome. Because the disease involves malignant tumor formations, it is generally considered life-threatening as it progresses.
Complications
Due to Li-Fraumeni syndrome, malignant tumors form. These can lead to the death of the patient in the long term. In most cases, these tumors form when the patient is still young. However, the further course of the disease strongly depends on the affected organs, so that a general course of this disease usually cannot be predicted. In general, the patient suffers from fatigue and a reduced ability to cope with stress.Patients may also suffer from pain or various deformities and limitations in everyday life. The quality of life of the affected person is significantly reduced due to Li-Fraumeni syndrome. Parents and relatives also suffer greatly from the discomfort of this syndrome and may develop psychological discomfort and depression as a result. The earlier the tumors are detected, the better they can be removed and treated. However, a complete cure cannot be guaranteed. In some cases, the symptoms of Li-Fraumeni syndrome thus lead to the death of the affected person or to a significant reduction in life expectancy. Chemotherapy can be used to limit some of the symptoms. However, the therapy itself is associated with various side effects.
When should you go to the doctor?
Li-Fraumeni syndrome is initially manifested by general symptoms such as fatigue, weight loss, and malaise. These signs of illness usually indicate a serious condition, especially if they occur over a long period of time, and therefore require medical attention. Affected individuals should quickly inform their family doctor if they experience pain or even skin changes. Swellings or nodules are clear warning signs that are best examined immediately. Risk groups include cancer patients and people with a close family history of rare syndrome or other cancer. The disease occurs before the age of 45, usually in childhood and adolescence, and progresses progressively. Li-Fraumeni syndrome is treated by a primary care physician or a dermatologist. Severe conditions may need to be treated in a specialized clinic. Basically, the hereditary disease is a severe condition that requires close monitoring by a specialist. In addition, there is an increased risk of recurrence, which is why further medical examinations are indicated even after removal of the tumors.
Treatment and therapy
Once Li-Fraumeni syndrome has been diagnosed by the treating physician, the individual therapy depends on the patient’s health status. In most cases, a cancer is already present, which has led to the visit to the doctor and the diagnosis. This must, of course, be treated as a matter of priority in order not to endanger the life of the person concerned. Depending on the type of cancer and the stage it is in, chemotherapy will most likely take place. This destroys the cancer cells in the body and prevents them from spreading further in the organism. In some circumstances, surgery may also be recommended to remove tumors that have already developed. Afterwards, comprehensive follow-up care and later regular routine examinations should take place in order to detect further tumor formations at an early stage. There is still no effective therapy for Li-Fraumeni syndrome itself. However, recent research is experimenting with introducing healthy DNA into the cancer cells to subsequently generate healthy genetic material and prevent further tumor formation. Upon request, patients with Li-Fraumeni syndrome can receive the drug Advexin, which has not yet been approved, if other treatment approaches are unsuccessful for them and their lives are acutely threatened by the progression of the disease.
Outlook and prognosis
Li-Fraumeni syndrome is characterized by an unfavorable prognosis. Already in the first years of life, patients suffer malignant tumors due to the syndrome. Without treatment, premature death occurs relatively quickly. Life expectancy is often estimated at about five years. Because it is a genetic disease, no causative therapy can be applied. Researchers and scientists are prohibited from altering human genetics due to current legislation. Therefore, the treating physicians try to recognize the symptoms of the disease as early as possible as well as to treat it. Nevertheless, it is basically a race against time. Due to the mutation of the genes, different tumors are formed in the organism. The cancer cells divide and are transported via the bloodstream to other parts of the body. Metastases often develop there, although cancer therapy for a tumor in another physical region is taking place at the same time. All developing tumors basically have a malignant growth.The quality of life is significantly reduced, as the affected person will experience several bouts of cancer in the course of his or her life due to the effects of the disease. Despite all efforts, life expectancy is significantly reduced overall. In only about half of those with the disease, the risk of subsequent tumor disease is at the level of a healthy person.
Prevention
Because Li-Fraumeni syndrome is in most cases a gene mutation that is inherited, prevention in the true sense is not possible. If the first signs of cancer appear, it is of course always necessary to consult a doctor quickly. Especially in the case of tumor formation at a young age and in the case of a family history of cancer, an examination regarding Li-Fraumeni syndrome is also advisable in this context in order to be able to take further appropriate steps.
Follow-up
After the actual cancer treatment, affected individuals require ongoing care. In addition to regular medical examinations and the use of further therapies, aftercare also includes a change in lifestyle. Those affected must now rebuild their quality of life. The support of the responsible physicians as well as relatives and friends is important in order to find a good way of dealing with the disease. Attending a support group can also be an important aspect of aftercare. Depending on the type of cancer, the aftercare plan is drawn up together with the doctor. It is based on the symptoms of the type of cancer, the general course of the disease and the prognosis. In the first phase, when patients are still coping with the consequences of the disease and treatment, aftercare is particularly important. It is crucial to support patients until remission is achieved.
Here’s what you can do yourself
In general, the options for self-help in Li-Fraumeni syndrome are very limited. In this regard, the course and treatment of this syndrome are also very dependent on the exact region of tumor formation, making it difficult to predict a prognosis. However, patients with this syndrome are dependent on medical treatment to remove it. Regular examinations help to detect and treat tumors early in Li-Fraumeni syndrome. This can increase the life expectancy of the affected person. Especially the internal organs should be examined regularly. Furthermore, the patient should lead a healthy lifestyle and abstain from addictive substances in order not to further promote tumor formation. In the case of psychological complaints, discussions with close friends or with the patient’s own family very often help. Contact with other patients affected by Li-Fraumeni syndrome can also have a positive effect on the disease and further alleviate psychological complaints. Also an exchange of information can take place, which can possibly improve the quality of life of the affected person. Despite permanent treatment and regular examinations, Li-Fraumeni syndrome eventually leads to a reduced life expectancy of the affected person.
