Thalidomide-contergan embryopathy causes developmental malformations of the embryo in early pregnancy. The cause is exposure to the harmful substance thalidomide or thalidomide. Therapy of affected patients takes place in an interdisciplinary team of physicians and usually lasts a lifetime.
What is thalidomide-contergan embryopathy?
Embryogenetic developmental disorders caused by adverse effects during the first three months of pregnancy are embryopathies. Thalidomide-associated malformations are referred to as thalidomide-contergan embryopathy. Thalidomide, formerly also known as thalidomide, is a glutamic acid derivative that has depressant effects on the central nervous system. The immune system is downregulated by the drug, so that anti-inflammatory properties are also associated with the drug. Due to its active ingredients, thalidomide belongs to the piperidinediones and thus represents a structural modification of barbiturates. In Germany, the drug thalidomide was dispensed without prescription in the 1950s and was used primarily as a sleeping pill and sedative. Due to the side effects when taken, the biggest scandal of the German pharmaceutical industry developed in the 1970s. Charges of bodily injury and negligent homicide against the Grünenthal company accumulated. Many of the patients suffered from polyneuritis after taking the drug. In addition, taking thalidomide during the first three months of pregnancy showed harmful effects on embryogenesis, so that 10,000 children were born with thalidomide-associated malformations.
Causes
Thalidomide-contergan embryopathies are caused by thalidomide-containing drugs taken by women during the first three months of pregnancy. In this early developmental phase of the embryo, the unborn child is particularly susceptible to all external influences. For this reason, pregnancies are usually kept secret until the fourth month. Often the embryo still aborts in response to exposure to harmful substances during the first three months. Thalidomide-contergan embryopathies can also cause miscarriage, depending on their severity. If the child survives the harmful substance exposure and is born with it, the embryopathy manifests itself in malformations. If the expectant mother has taken thalidomide-containing drugs between day 34 and day 38 after her last menstrual period, the toxicant exposure usually results in facial paralysis and missing auricles. Exposure between day 40 and day 44 results in malformations of the arms. Between day 43 and day 46, malformations of the legs may also result from exposure. Exposure to drugs such as thalidomide between day 48 and day 50 results in thumb malformations and rectal constrictions. In particular, inhibition of ligase activity associated with the drug is a major cause of the malformations. This inhibition results from binding of thalidomide to cereblon.
Symptoms, complaints, and signs
Patients of thalidomide-contergan embryopathy suffer from a wide range of symptoms that can vary widely in severity and correlate with the degree as well as exact timing of exposure. The body structures most commonly affected by damage are the arms. Malformations of the arms even occur in more than half of all cases of thalidomide ingestion during pregnancy. In about a quarter of all cases, the legs are also affected by malformations in addition to the arms. The malformations can correspond to deformities or underdevelopments, although the lack of a leg or arm is also within the realm of possibility. In slightly more than ten percent of all cases, affected individuals also show malformations of the ears, which can extend from the auricles to above the inner ear. The arms and ears are affected simultaneously in about five percent of all cases. Malformations of the internal organs were observed in only about two percent of all affected persons. Due to malpositions and deformities, patients often quickly suffer from degenerative changes in the joints, which can be accompanied by pain in the shoulders, elbows, hips, hands or spine. In addition to these sequelae, mental illness may occur as a result of the deformities.
Diagnosis and course of the disease
The diagnosis of thalidomide-contergan embryopathy is usually made visually by the physician with an appropriate history.The characteristic malformations are sufficient for a reliable diagnosis if the mother reports thalidomide use during pregnancy. In order to get a picture of all malformations, the physician usually arranges for a variety of imaging. These include, for example, images of the internal organs. The prognosis of patients depends greatly on the malformations present and the severity and duration of thalidomide exposure in each individual case.
Complications
Affected individuals with thalidomide-contergan embryopathy must always expect severe complications due to the various medical conditions. Malformations of the arms generally lead to a reduced quality of life and also have a significant psychological impact on patients and their parents. The malformations themselves can be accompanied by metabolic disorders, circulatory problems, infections and other complications. Malformations of the internal organs also have serious consequences, depending on which organ is affected. Thus, various kidney and liver diseases, disorders of the cardiovascular system and chronic gastrointestinal complaints may occur. Degenerative changes in the joints are associated with pain, misalignment and premature joint wear. An auricular deformity has mainly psychological consequences for those affected. They often suffer from teasing or bullying due to the visual blemish and become aggressive or depressed as a result of social exclusion. TCE therapy is also associated with risks. Surgical procedures are usually complex and can cause further damage to organs, joints, muscles and tendons. Typical complications include infection, bleeding, post-operative hemorrhage, wound healing problems, and allergic reactions. If implants are inserted, there is a risk that the organism will reject them after months or years.
When should you go to the doctor?
In the case of thalidomide-contergan embryopathy, the affected person is always dependent on medical examination and treatment, as it cannot heal on its own. The earlier the disease is detected and treated, the better is usually the further course. Therefore, a doctor should be contacted at the first symptoms and signs of the disease to prevent further deterioration of the symptoms. As a rule, the doctor should be contacted in case of thalidomide-contergan embryopathy if the affected person suffers from various malformations. These malformations may affect the ears or other areas of the face. It is not uncommon for psychological complaints to be indicative of thalidomide-contergan embryopathy and must also be investigated. Most affected individuals also suffer from severe pain in the shoulders or very stiff joints. If these symptoms occur, a general practitioner or pediatrician should be contacted. Further treatment of thalidomide-contergan embryopathy always depends on the exact symptoms and their severity. It is then carried out by a specialist. As a rule, the life expectancy of the affected person is not reduced by this disease.
Treatment and therapy
Therapeutic care for people with thalidomide-contergan embryopathy is provided by an interdisciplinary treatment team of physicians from various specialties, physical therapists, occupational therapists, psychologists, and social workers. As a rule, lifelong care is required, which is associated with high personnel and financial costs. In the case of malformations of the internal organs, the patient’s life may be at stake. For this reason, these malformations initially receive the highest attention. Invasive surgical corrections of the organic defects take place as far as possible. In extreme cases, organ transplantation may become necessary in the long run. Malformations of the arms and legs may also be treated surgically. However, since the malformations often involve the missing attachment of limbs or limbs, prosthetic fitting is often the best option. In occupational therapy, patients learn how to cope with the disease on a daily basis and, if necessary, learn compensation strategies or the use of assistive devices. Social workers primarily fulfill an advisory function when it comes to obtaining assistance from aid organizations. In psychological sessions, patients process their everyday challenges and learn coping strategies.In this way, the risk of psychological sequelae can be minimized. If deformities of the joints are present, arthrosis often occurs as a consequence. In such a case, the provision of artificial joints may become necessary.
Prevention
Expectant mothers can prevent thalidomide-contergan embryopathy by not taking medications associated with it during pregnancy. If medications cannot be discontinued for health reasons, the decision not to have a child of one’s own is considered the only preventive measure.
Follow-up
The aftercare of a thalidomide-contergan embryopathy is highly dependent on the malformations caused by the disease. In addition, a thalidomide-contergan embryopathy is usually treated for life, so traditional follow-up care is not required. However, there are certain deformities of the ears, bones and joints associated with thalidomide-contergan embryopathy that should be followed by aftercare treatment. In the case of bone and joint diseases, this should consist of physiotherapeutic exercises that ensure the mobility and resilience of joints and bones. In addition, permanent pain therapy may be necessary in this case. Therefore, in the case of deformities of bones and joints that are accompanied by pain, there should always be additional pain therapy. In addition to conservative, medicinal pain therapy, there are also many non-drug options that can provide pain relief. If malformations of the ears were present, regular check-ups with an ear, nose and throat specialist should be performed even after successful therapy in order to detect secondary diseases at an early stage. Malformations of the arms and legs can also be accompanied by pain for those affected, which can be very stressful psychologically. This also applies to malformations that require lifelong therapy and cause severe movement restrictions. Additional psychotherapy, if necessary also with accompanying medicinal psychiatric treatment, can provide relief here and help patients to cope with their limitations.
What you can do yourself
Children affected by thalidomide-contergan embryopathy usually needed assistance with everyday tasks. Accompanying medical and therapeutic treatment, which consisted of a variety of operations, medication administration and physiotherapy, among other things, children with the disease were supported at home. To this end, the home was equipped to meet the needs of the disabled, insofar as this was possible in the 1960s. In addition, walking aids, a wheelchair and other aids had to be organized at an early stage. Subsequently, comprehensive education was important. Information material and books about thalidomide made it easier for the children affected to deal with their deformities. Nowadays, however, thalidomide-contergan embryopathy no longer occurs, since the drug is no longer prescribed and the affected patients are already adults. People who suffer from a malformation as a result of their mother taking thalidomide may be entitled to compensation. It is advisable to talk to a specialist doctor and a specialist lawyer for medical law. People who suffer from severe deformities usually have to perform physiotherapy for the rest of their lives and are limited in what they can do. However, quality of life can be improved by living a fuller lifestyle. The Bundesverband Contergangeschädigter e. V. (Federal Association of Contergan Damaged Persons) offers those affected further points of contact and information material.
