Rare Genetic Diseases: Tuberous Sclerosis Complex
Tuberous Sclerosis Complex (TSC) is a rare multisystem autosomal dominant genetic disease, which causes non cancerous tumours to grow in the brain and other vital organs, such as liver, kidneys or skin. Around 7–12 : 100,000 individuals are affected. The prognosis for affected individuals is highly variable and depends on the symptoms, but life expectancy is normal for the majority.
The physical manifestations of TSC are due to the formation of hamartia (malformed tissue), hamartomas (benign growths) and very rarely, cancerous hamartoblastomas. The symptoms include combination of seizures, intellectual disability, developmental delay, behavioural problems, skin abnormalities, lung disease and kidney disease.
Several subgroups of symptoms have been identified, however the most prevalent ones are neurological and neuropsychiatric. The complex causes growth of three particular brain tumours, which are: giant cell astrocytoma, cortical tubers and subependymal nodules. The effect of these on the brain leads to behavioural problems, seizures, developmental delay, and intellectual disability.
About 90% of affected individuals develop a range of neurodevelopmental, behavioural, psychiatric and psychosocial difficulties. The neuropsychiatric symptoms are less identified and often remain untreated. Patients usually suffer from sleeping difficulties, overactivity or impulsivity. There is a chance that they can also develop autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), anxiety disorder or depressive disorder. The intellectual development varies among the affected individuals, however, around 40% — 50% develop a normal IQ.
TSC has an autosomal dominant pattern of inheritance, variable expressivity and incomplete penetrance. ⅔ of the cases result from sporadic mutations, and not from inheritance, however, the affected individual can pass the mutated genes on the offspring.
Current genetic tests have trouble establishing the gene mutation in about 20% of the cases. So far two tumour suppressor genes have been identified: TSC1 and TSC2. TSC1 encodes for the protein hamartin and is located on chromosome 9 q34. TSC2 encodes for protein tuberin and is located on chromosome 16 p13.3. TSC2 causes a more severe form of TSC. Both proteins, hamartin and tuberin function as heterodimers which coordinate diverse extracellular and intracellular signals, cell growth and proliferation.
The treatment of TSC is focused on individual organs affected, thus a multidisciplinary team of medical professionals is required.
