Tuberous Sclerosis Complex (TSC)
DISEASE DEFINITION
Tuberous sclerosis complex (TSC) is a rare, genetic multisystem disease characterized by the formation of benign tumors (hamartomas) in various organs. The brain, skin, kidneys, heart, lungs and eyes are most frequently affected. The disease is highly variable - both in terms of the organs affected and the severity of the symptoms.
WHAT IS THE CAUSE?
TSC is triggered by mutations in the TSC1 or TSC2 genes. This disrupts the function of these so-called tumor suppressor genes, leading to overactivation of the mTOR signaling pathway and thus to uncontrolled cell growth and tumor formation. The mutations usually occur spontaneously but can also be inherited autosomal-dominantly from parents to their children.
SYMPTOMS
| Skin | TSC is a neurocutaneous syndrome. The following changes can occur as typical skin symptoms:
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| CNS | The changes in the Central nervous system (CNS) affect the brain and the behavior of the patients.
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| Eyes | occurrence of retinal hamartomas. | ||
| Heart | Rhabdomyomas of the heart usually occur in infancy or can even be an initial indication of the disease in ultrasound examinations before birth. They often regress spontaneously. | ||
| Lungs | Lymphangioleiomyomatosis (LAM) occur especially in adult women and can lead to shortness of breath and impaired lung function. | ||
| Kidneys | The most common TSC-associated kidney disease comprises three major phenotypes: angiomyolipomata (AML), cystic disease and rarely renal cell carcinoma (RCC). These phenotypes are not mutually exclusive and patients often have a combination of angiomyolipomata and cysts, or all three phenotypes. TSC-associated kidney disease can lead to complications and a deterioration in kidney function. |
DIAGNOSIS
Diagnosis is based on the clarification of typical clinical findings and the detection of a mutation in TSC1 or TSC2. In addition to the clinical and genetic examination, imaging procedures (ultrasound, MRI, CT) or the measurement of electrical brain waves (EEG) are also used to determine the involvement of the various organs. The TAND checklist supports the early detection of neuropsychiatric disorders.
There is international, regularly updated diagnostic criteria.
TREATMENT
A causal cure is not yet possible. Drug therapy options include anticonvulsants to treat epileptic seizures or mTOR inhibitors (everolimus, sirolimus) to restrict the growth of tumors in the brain or kidneys, for example.
Furthermore, symptom-oriented management often requires multidisciplinary care, whereby psychological and social support regarding neuropsychiatric disorders should not be neglected. Regular check-ups are essential in order to detect and treat complications as early as possible.
PROGNOSIS
The prognosis depends on the severity and extent of organ involvement. Possible serious complications are: Status epilepticus, giant cell astrocytoma, bleeding from angiomyolipomas, hypertension or kidney failure. Cardiac rhabdomyomas usually regress on their own.
TSC is a lifelong, chronic disease whose management has been significantly improved by modern therapy concepts and interdisciplinary care.