Tuberous sclerosis is a hereditary disease associated with various malformations of the brain and skin changes. The condition is also known as Bourneville-Pringle syndrome after its discoverers.
What is tuberous sclerosis?
Tuberous sclerosis is called tuberous sclerosis complex (TSC) in English. The disease belongs to the group of phakomatoses. Phakomatoses are diseases characterized by malformations of the skin and nervous system. Besides tuberous sclerosis, neurofibromatoses and Peutz-Jeghers syndrome also belong to phakomatoses. One newborn in every 8000 births is affected by the disease. The disease is inherited. Malformations and tumors of the brain, developmental disorders, skin changes and organ changes are found. Tuberous sclerosis cannot be treated causally. Treatment is purely symptomatic. People with mild tuberous sclerosis usually lead normal lives. However, in severe disease, life expectancy is limited.
Causes
Tuberous sclerosis is an inherited disease. It is inherited in an autosomal-dominant manner. In autosomal dominant inheritance, the genetic information is located on one of the 22 pairs of autosomes. The disease is inherited regardless of gender. The children of a person with the disease have a 50 percent risk of inheriting the diseased allele and thus also becoming ill. If both parents suffer from tuberous sclerosis and are also heterozygous trait carriers, the risk of disease increases to 75 percent. If one parent is homozygous, i.e. carries two defective alleles, the risk of disease is 100 percent. In 30 percent of all patients, the disease is inherited from both father and mother. In the remaining 70 percent, the disease occurs only sporadically. Diseases caused by new mutations are possible. Even if tuberous sclerosis is only very mild in affected parents, there is a possibility that the children will later suffer from a very pronounced form of the disease.
Symptoms, complaints, and signs
The tumor-like changes and malformations in the brain are often detected at a very early age in those with the disease. Cortical glioneuronal hamartomas are found in the cerebral cortex. Hamartomas are tumors that originate from malformed embryonic tissue. Protrusions develop, resulting in cognitive impairment. Epilepsies can also be caused by these tuberosities. So-called subependymal giant cell astrocytomas and subependymal nodules near the ventricular system also form. Impairment of the ventricular system typically results in hydrocephalus. Hydrocephalus is the term used to describe an abnormal dilatation of the cerebral ventricles that are filled with fluid. Hydrocephalus is also called hydrocephalus. Epileptic seizures are typical of tuberous sclerosis. They often occur in the first months of life. West syndrome may develop in infants. This is a generalized malignant epilepsy associated with flash seizures, nodding seizures, and salaam seizures. The more frequent the seizures, the more learning difficulties the children have. Learning disabilities are a major problem in tuberous sclerosis. Development is often impaired. Difficulties occur, especially in speech and movement development. Behavioral problems may also occur. However, half of all patients with tuberous sclerosis have a normal intelligence quotient. Severe limitations are present in 30 percent of patients. Skin changes can occur in varying degrees. Initially, harmless pigmentary abnormalities appear. Later in childhood, reddish nodules develop in the area of the nasolabial folds. These are also called angiofibromas. Typical for the disease are also “shagreen patches”. These are slightly raised hardened skin lesions around the lower back. In one quarter of patients, reddish fibromatous nodules develop at the nail fold. These are also called Koenen’s tumor. Tumors may also occur in other organ systems. The kidneys often have cysts or angiomyolipomas. Normally, however, these tumorous changes do not cause any symptoms. However, there is a risk of malignant degeneration of the tumors. The lungs and other organs of the body can also develop tumors in the course of the disease.
Diagnosis and course of the disease
Diagnosis of tuberous sclerosis is difficult, especially in younger children. Major features of the disease include angiofibromas of the face, nail fold tumors, tuberosities of the cerebral cortex, and hamartomas of the retina. Secondary features include confetti spots of the skin, renal cysts, and unpigmented spots of the retina. Tuberous sclerosis is considered confirmed when two major features or one major feature and two minor features are present. If one major feature and one minor feature are present, tuberous sclerosis is likely. If one major feature or two minor features are present, tuberous sclerosis is at least suspected. If the disease is suspected, various imaging techniques such as ultrasound or computed tomography are used. The diagnosis can be confirmed by the detection of a gene mutation by molecular genetics. However, a mutation of the TSC genes can be detected in only 85 percent of all cases of the disease.
Complications
In this disease, affected individuals primarily suffer from various malformations that occur directly in the brain. This usually results in cognitive and motor impairments. Furthermore, the disease can also lead to mental retardation, so that the affected persons are always dependent on the help of other people in their daily lives. The disease can also lead to epileptic seizures and, in the worst case, to the death of the affected person. The patients also suffer from severe learning disorders and therefore require intensive care. In some cases, the disease can also cause pigmentary disorders, which, however, do not have any further negative impact on the patient’s health. The internal organs can be affected by tumors and must therefore be examined regularly. The life expectancy of the affected person may also be significantly reduced. Since a causal treatment of this disease is usually not possible, only the individual symptoms can be limited. This does not lead to further complications. With the help of medication, the epileptic seizures can be resolved. However, a complete cure is not achieved. In many cases, the parents and relatives also need psychological treatment.
When should one go to the doctor?
Since self-healing cannot occur with this disease, the affected person must see a doctor. This is the only way to prevent further complications. The earlier the disease is detected and treated, the better the further course. A doctor should be contacted if the affected person has various malformations of the brain. Epilepsies can also indicate this disease and should also be examined by a doctor. In some cases, the affected person also suffers from pitching seizures due to this disease, so that children may experience a significant delay in development. At the same time, complaints in learning or speaking also strongly indicate this disease. Changes on the skin can also indicate these complaints. The disease itself can be detected by a pediatrician or by a general practitioner. In most cases, the treatment itself is then carried out by a specialist and depends on the exact manifestation of the complaints.
Treatment and therapy
A causal therapy of the disease is currently not possible. Treatment is purely symptomatic and largely focused on the epilepsy. Antiepileptic drugs (anticonvulsants) are used to treat epilepsy. The aim of these drugs is to prevent epileptic seizures. In about 80 percent of patients, seizure freedom can be achieved with the help of these drugs. If it is not possible to prevent seizures completely, at least the severity and frequency are reduced.
Prevention
Tuberous sclerosis cannot be prevented. Families in which family members already have tuberous sclerosis are recommended to undergo molecular genetic testing if they wish to have children.
Follow-up
There is no causal therapy for tuberous sclerosis. Therapy is only symptomatic and is largely related to epilepsy. Affected individuals are extremely limited in their lives with the disease. Help from the family and relatives cannot be dispensed with. It is recommended that affected persons undergo counseling with a psychologist.This can help how best to deal with the disease and make everyday life more worth living. Going to a self-help group would also only be beneficial for those affected. There you can get tips and other opinions on how to live with tuberous sclerosis. Above all, however, affected persons can talk there with likewise affected persons and do not feel alone. In any case, those affected should pay attention to an extremely healthy lifestyle. This means that nicotine, alcohol and drugs should be avoided. Attention should also be paid to a balanced diet rich in vitamins. Affected persons must make sure that they are not overweight. For this reason, sufficient exercise should be done. In any case, attention must be paid to a healthy sleep rhythm. If affected persons have a desire to have children, it is recommended to undergo genetic counseling in advance.
What you can do yourself
Because this condition is genetic, it cannot be cured. But its symptoms can be alleviated – depending on the severity. Here, first and foremost, the parents of affected children are called upon. The earlier the cognitive and motor impairments are recognized, the faster they can be treated and compensated. Medications can be given to counteract the epileptic seizures. The parents must monitor the child’s intake of medication until the child is old enough to cope with the disease on his or her own. Depending on the severity of the symptoms, tuberous sclerosis is a very distressing disease. Therefore, in many cases, it is necessary for affected individuals and their families to undergo adjunctive psychotherapy. They may also benefit from attending a self-help group. The Tuberous Sclerosis Association of Germany provides addresses and information on this. (www.tsdev.org). If the affected persons need support in coping with their everyday life, the above-mentioned association also provides practical advice on socio-legal assistance. As with all chronic illnesses, those affected should pay attention to a healthy lifestyle. This includes eating a diet rich in vitamins and nutrients, exercising, avoiding nicotine and alcohol, and ensuring a regular sleep/wake rhythm. Adult patients with tuberous sclerosis who have a desire to have children should seek genetic counseling in advance.