Tuberous sclerosis Flashcards
What are the causes of tuberous sclerosis
- Genetic inheritance (autosomal dominant); majority of cases
- De-novo mutation; minority of cases
What do the non-mutated TSC-genes normally do?
The non-mutated TSC genes normally produce proteins that form a complex to inhibit mTOR. This inhibition is crucial to prevent excessive protein synthesis and uncontrolled cell growth.
Explain how TSC symptoms can be seen on the skin
o White spots (depigmentation) due to abnormal formation of cells
o Special kind of acne (small tumors)
o Benign growths on nails (fibromas)
o Benign growths at the level of the gums
o Fibrous plaques on forehead, …
Explain how TSC symtpoms can affect cognitive abilities
o Mental retardation
o Social communicative, language, attention, executive functions,memory
o Fine motor problems
Explain how TSC can cause behavioural problems
o Autism, ADHD, aggression, resistant to change
oNegativity, emotionally fragile, depressive episodes, anxiety disorders, sleep disorders, psychotic disroders related to epilepsy.
discuss the onset of symptoms of TSC
o Cardiac symptoms start early on, but they disappear
relatively quickly by themselves.
o Renal symptoms start early on and go on the age of 60.
o Cerebral early on into early adulthood (dangerous because
that’s a critical time for brain development)
o Skin symptoms start during puberty and leave at the age of 40.
o Lungs often from adult hood onwards.
epislepsy in TSC patients (percentages)
o Epilepsy in 90% of TSC patients
o 71% of patients develop seizures in the first 2 years of life.
How do we know the patient is having a seizure apart from looking at the body language?
An EEG
o An EEG picks up the electrical signals that are produced by the brain.
o During these epileptic seizures–we can’t see any sort of constant pattern in electrical signals–this means that there’s no structure in brain activity at all.
o During the time that these kids are having these seizures, they can’t learn anything new.
discuss individual differences of TSC patients
o How big the tumors are and where they’re located.
o Whether or not the tumors can be surgically removed.
o Different amount of attacks
o the same mutations can cause different gradations of TSC
What are the different types of epilepsies in TSC
- Epileptic spasms/Infantile spasms (West Syndrome)
- Focal epilepsy
- Symptomatic generalized epilepsy (Lennox Gastaut epilepsy)
discuss the diagnosis of TSC
Prenatal diagnosis is possible today, using ultrasound or MRI; detecting tumor (especially in heart; rhabdomyomas a lot of certainty for TSC)
o Discussion about abortion: there is also a chance that the child will have little or no problems with TSC
Age at diagnosis is often very early (20% even antenatal(before birth), the rest mainly in the first year of life;
then treatment is certainly still possible, but will in any case have less effect than if from birth)
Discuss the treatment of TSC
- Ketogenic diet can sometimes help against epilepsy.
- mTOR inhibitors (e.g., everolimus)
- Study: strong decrease and significant difference with placebo group; but poor decrease to 50%
- Declaration: pts already 2 years at the start of treatment; the earlier, the greater the effect!
What does autosomal dominant mean
o Autosomal = the gene in question is located on one of the non-sex chromosomes
o Dominant=a single copy of the mutated gene is enough to cause the disorder.
what does de-novo mutation mean
Fertilization mutations, in child itself
what are the 2 most common mutations of TSC
o Chromosome 9, TSC1 gene
o Chromosome 16, TSC2 gene (MORE SERIOUS)
