Klinische Topics alles Flashcards
1
Q
What are the diffferent types of cancer?
A
- Carcinoma: lungs, breasts, colon, prostate
- Leukaemia: bloodstream
- Lymphoma: lymphnodes
- Sarcoma: fat, bone, muscle
2
Q
What cells stimulate cell suicide?
A
tumour suppressor genes
3
Q
What is apoptosis?
A
cell suicide
4
Q
What is metastasis
A
cancer cells spread via blood or lymphatic vessels to other sites.
5
Q
What are the causes of breast cancer?
A
General: viruses and bacteria, chemicals, radiation, diet, hormones INTERACTION WITH heredity
> usually lots of factors combined, with most people we don’t even know the cause; it really depends on your ability to destroy bad cells
6
Q
What are the risk factors for cancer in general?
A
» Meat consumption - colon cancer
» Cigarette consumption - lung cancer
» Combination of cigarettes and alcohol - cancer of the oesophagus
» Ultraviolet radiation - skin cancer
» Atomic radiation (X-rays) - leukemia
» Viruses and bacteria
7
Q
WHat are the hereditary risk factors of breast cancer?
A
BRCA1 and BRCA2 gene mutated – Only 1/20 cases due to heredity
The BRCA1 and BRCA2 gene = genes that produce proteins that help repair damaged DNA.
* Chromosome 17, BRCA1 gene (also play a slight role in ovarian cancer)
* Chromosome 13, BRCA2 gene (also play a slight role in pancreas, prostate, melanoma cancer).
* Autosomal dominant
8
Q
What are the controllable risk factors of breast cancer?
A
not having children or having them late, some types of birth control, not breastfeeding, night work, overweight, etc
8
Q
What are the uncontrollable risk factors of breast cancer?
A
Gender (more in women), genes, menstruation, ethnicity, age, denser breast tissue, etc.
9
Q
What happens in the case of DNA damage when developing breast cancer?
A
- One tiny change in a DNA sequence (a single base change) can cause cancer.
- In case of the DNA damage - clearing systems in place (e.g., P53 gene) and ensure apoptosis.
- HOWEVER due to a defect (the risk factors mentioned above) the clearing systems don’t activate.
10
Q
Benign vs. malignant
A
Benign
* In situ (original position)
* Abnormal growth but doesn’t spread.
* Not life-threatening
* Not cancerous
Malignant
1. Non-invasive – precancerous
* Still in situ
* Close to nearby tissue
2. Invasive – cancerous
* Spreads to other organs
11
Q
What are the different types of breast cancer?
A
- DCIS
- IDC
- LCIS
- ILS
12
Q
What are the signs of breast cancer?
A
» Lump/swelling in chest or armpit.
» Pain in armpits (many lymphnodes swollen)
» Redness of breast
» Rash around nipples
» Area of thickened tissue in skin
» Discharge from nipple, may contain blood.
13
Q
How do we diagnose breast cancer?
A
» Self–examination
» Imaging tests: ultrasound, MRI, mammography
» Biopsy to confirm whether its benign or malignant.
14
Q
What’s the treatment of breast cancer?
A
» Surgical removal of cancer in situ or full breast.
» Radiation (only if it’s very invasive)
» Chemotherapy
» Targeted drug therapy= specifically against breast cancer cells
» Hormone therapy against hormone - sensitive cells
* ER – estrogen sensitive.
* PR – progesterone sensitive.
15
Q
Explain the TNM staging system
A
Based on:
* T = tumor size and spread
* N = spread to lymph nodes
* M = metastasis happened?
16
Q
What are the different stages of (breast) cancer
A
- STAGE 0: non-invasive
- STAGE1:growth(<2cm), not yet invasive
- STAGE 2A and B: growth + whether or not it’s spread to lymph nodes – from now on cancer.
- STAGE 3A, B and C: growth, spreading further to lymph nodes, skin, and chest.
- STAGE 4: metastasis has happened.
17
Q
…(ratio) vrouwen heeft in de loop van haar leven kanker op de borst
A
1/8
18
Q
Give some extra details on sarcoma as a type of cancer
A
metastises quickly
bad prognosis
gets noticed very late
19
Q
explain the role of viruses in breast cancer
A
They’ll integrate into our cells and DNA, allowing themselves to replicate. They can change DNA, resulting in the production of bad cells
> different viruses for different types of cancer
20
Q
DCIS
A
non-invasive, stays in the milk ducts, can become invasive
21
Q
IDC
A
most common breast cancer, wall of lactiferous ducts – causing growth/invasion of surrounding breast tissue – spreads to lymph nodes and then metastases to other organs.
> accounts for 80% of invasive breast cancers!!
22
Q
LCIS
A
in situ, non-invasive, stays in lobules, can become invasive
23
Q
ILS
A
10% of breast cancer cases, formed in lobules, invades
nearby tissues via lymphatic vessels and metastases to other organs.
24
ductal carcinoma
in lactiferous ducts
25
lobular carcinoma
in lobules
26
Where's the first place breast cancer can metastise to
the glands in the armpit area(the sentinel gland) and it's the first place they check during surgery/examinations/ etc.
27
lifetime risks brca1/2 associated cancers
breast cancer: 50-70%
secondary breast cancer (or stage IV breast cancer): 40-50%
ovarian cancer: 15-55% (BRCA 1> BRCA 2)
28
BRCA 1 and BRCA 2 related risks of other cancers
- male breast cancer
- pancreatic cancer
- prostate cancer
- melanoma
1. BRCA 2> BRCA 1
2. BRCA 2
3. BRCA 2
4. BRCA 2
29
incidence of breast cancer by race
caucasian > african > asians > hispanic > native american
30
survival rates breast cancer vs. stages
Stage 0: 100%
Stage 1: 100%
Stage 2: 93%
Stage 3: 72%
Stage 4: 22%
31
What happens during a myocardial infarction?
1. Accumulation of fat (cholesterol) in the intima = atherosclerotic plaque = atherosclerosis
o Intima = layer underneath the top layer of cells in arteries.
2. The accumulation of fat results in the lumen becoming smaller (creating a higher blood pressure).
3. At some point, an ulcer forms on top of the (ruptured) atherosclerotic plaque.
4. Our body reacts to this by forming a blood clot on top of it – increasing the risk of the artery getting blocked.
5. If the artery gets blocked by a blood clot (thrombosis), oxygen can’t reach certain places in the heart – resulting in a myocardial infarction.
32
What are the uncontrollable risk factors of a myocardial infarction?
Increasing age – male gender – family history – genetic abnormalities
> this doesn't mean you are going ot get it for sure, there are tihngs you can do to prevent it
33
What are the lesser, uncertain and unmodifiable risk factors of a myocardial infarction?
Obesity – physical inactivity – postmenopausal oestrogen deficiency – high carbohydrate intake – hardened unsaturated fat intake – chlamydia pneumoniae infection – high LDL
34
What are the potentially controllable risk factors op a myocardial infarction?
1. hyperlipidaemia
2. hypertension
3. cigarette smoking
4. diabetes
5. C reactive protein
35
Explain hyperlipideamia in regards to myocardial infarction
**= excess of fats/lipids in blood**
o Cholesterol is important but only in certain amounts.
o We have 2 different types of cholesterol in our body.
1. LDL:Cholesterol produced by the liver that gets sentout to all our organs.
2. HDL:cholesterol that returns to the liver.
o The optimal situation = Low LDL and high HDL
o Factors that determine cholesterol levels:
1. Polyunsaturatedfats+omega-3 fatty acids + sports + limited alcohol consumption -> reduction of LDL cholesterol
2. Unsaturated fats(trans) +obesity +smoking -> LDL accumulation
36
What are the three types of atherosclerotic plaque build-up
1. Aneurysm and rupture: rupture of the coronary artery
2. Occlusion(blockage) by thrombus
3. Critical stenosis: full blockage of the artery
37
Zone of necrosis
If blood doesn’t reach the designated areas in the heart, that heart-tissue can die
38
transmural infarct
along the endocardium (=the inner surface layer)
39
ischemia
a condition in which blood flow is restricted/reduced in certain parts
40
IHD
ischemic heart disease
41
Patients with IDH fall into two large groups:
1=chronic
2=acute
1. CAD = coronary artery disease
= Commonly present with stable angina pectoris (chest pain)
» Episodic clinical syndrome
» Usually crescendo-decrescendo in nature
» Typically lasts 2-5 minutes.
» Caused by exertion or emotion.
2. Acute coronary syndromes
a. NSTEMI = unstable angina pectoris and non-ST-elevation.
» Myocardial ischemia with no evidence of muscle death
» Can occur at rest.
» >10 minutes
» Severe and of new onset (within last 4-6 weeks)
» Occurs with a crescendo pattern (gets worse)
b. STEMI=acutemyocardialinfarctionwithST-elevation.
» Irreversible necrosis
» Commonly known as heart attack.
42
What are the signs of an infarction?
» Pain, discomfort in chest (Levine's sign = grab to thorax, very typical)
» Dizzy, vomiting, lightheaded, diaphoresis
» Pain jaw, neck, back
» Pain in arm/shoulder (usually left)
» Shortness of breath (dyspnoea)
» 20-30% no symptoms: sudden and silent death (often diabetic, elderly, hypertension)
43
How do we clinically assess if someone had a myocardial infarction?
1. ECGchanges:STsegmentelevation
2.Blood levels :waste materials of the cardiac tissue increase (we don’t use this to diagnose, rather to rule out the myocardial infarction)
44
Treatment of a myocardial infarction (medication)
o Statins:i nhibit formation of atherosclerotic plaques -> Inhibits cholesterol metabolism
o Aspirin: less blood clotting (not a drug that's made for that but the side effect of the drug helps)
45
What (surgical) procedures can be done after a myocardial infarction?
**1.Angioplasty: **insertion of catheter through the groin towards the blocked artery via a bloodvessel - once in place, the balloon gets inflated -> presses plaque against sides of the artery -> widening the lumen .
**2. Coronary artery by pass (CABG):** healthy blood vessel get removed from leg/arm/chest -> blocked vessel gets replaced by new one.
**3. Transmyocardial laser revascularization**
46
... % of the cases die from a myocardial infarction due to ...
33%
cardiac arrythmias
47
why is a myocardial infarction a chronic disease
because it's a progressive condition characterised by the build up of plaque in arteries over time
48
LDL
the primary cholesterol that builds up in the intima
49
# HD
HDL
ensures that excess cholesterol is transported back to the liver
50
talk about alcohol consumption and a myocardial infarction
drinking a bit of alcohol is good for this situation!!
51
smoking one pack of cigarettes a day increases the myocardial death rate by ... %
200%
52
talk about hypertension in regards to myocardial infarction
it's worse for a brain infarction than a myocardial infarction
o 60% higher risk of atherosclerosis and eventually also myocardial infarction.
o Must be treated; if not, large portion will eventually die (to blockage of blood vessels, or heart failure)
o Gradually increases; slumbering, silent killer (from the age of 20!); you only notice it during critical stages
53
"Episodic clinical syndrome" explain in regards to CAD
the artery isnt completely closed but occasionally the blood doesn't flow through properly, causing occasional short pains
54
what does unstable angina tell us
it usually indicates that a myocardial infarctoin is nearby and is treated very seriously
55
what does nonST elevation tell us
that a myocardial infarction hasn't happened YET
56
diaphoresis
excessive sweating
57
palpitations
rapid pounding heartbeats
58
dyspnoea
shortness of breath
59
explain troponin levels in regards to myocardial infarction
if you have an infarction, troponine increases, the higher troponine, the worse the infarction
60
Explain cystic fibrosis
**Autosomal recessive disease (mutation in the CTFR gene)**
* The gene codes for an epithelial chloride channel
* There are 1000 different types of mutations ont hat gene,that all lead to cystic fibrosis
* The mutation is important for the transport of ions in and out of the cell.
* The disturbed transport of water and electrolytes results in an abnormal viscosity (thick & stickyfluid) of all exocrine secretions.
* Occurs in many organs–lungs is most important–pancreas, liver, ovaries & sperm (causes infertility)
61
What are the symptoms of cystic fibrosis?
* Lungs – sinusitis/nasalpolyps and/or bronchial in fections
* Pancreas- Exocrine pancreas insufficiency (= PI = insufficient digestive enzymes) and/or endocrine PI
* Liver/gut–liver fibrosis and/or meconium ileus and/or constipation.
* Other–salt loss in sweat and/or male infertility
62
What are the first symptoms of cystic fibrosis
o Chronic or recurrent respiratory infections
o Weight stagnation
o A lot of crying and always hungry
o Steatorrhea
o Meconium ileus
o Signs of malabsorption
63
explain the pancreas' exocrine function in relation to cystic fibrosis
» The exocrine function = provides enzymes for digestion
o The chloride channels are blocked or don’t work – this causes a build-up of thick mucus – this results in digestive enzymes being unable to pass through the membrane.
o This eventually results in less to no digestion & therefor having fats in stool.
64
explain the pancreas' endocrine function in
» The endocrine function = create and release important hormones (insulin) directly into the bloodstream
* Insulin gets produced by Langerhans cells in the pancreas – due to the build up of mucus, those cells lose function – less insulin in blood – more sugar in blood = hyperglycaemia
* Results in diabetes mellitus
65
What are the early symptoms of TYPE I diabetes?
» Glycosuria
» Polydipsia
» polyurea
» weight loss - due to indigestion and fluid loss
» secondary enuresis = temporary bedwetting
66
glycosuria
lots of glucose and water in urine
67
polydipsia
excessive thirst
68
What are the later symptoms of TYPE I diabetes
» Ketoacidosis
» Deeper breathing, hyperventilating (for converting H+ into CO2 => less acid) - (often misdiagnosed pneumonia)
» Dehydration
» Abdominal pain (often misdiagnosed as appendicitis)
» Shock, coma due to acidic blood
69
What's the treatment for TYPE I diabetes?
» Continuous insulin injections
» Distinguishing between hypoglycemia and hyperglycemia is difficult => always give a definite answer by giving a sugar cube, hypoglycemia will then disappear, hyper will not.
70
The lungs in regards to cystic fibrosis
Chronic, recurrent infections due to mucus accumulating in alveoli – breeding site for pathogens.
o Basic diseases (starts with recurring infections !!!!!)
o More intense; pseudomonas aeruginosa
Lung obstruction, progressive lung damage and destruction => bronchiectasis (bronchial bulges, lung cavities)
71
Discuss treatment for cystic fibrosis in regards to the lungs
EARLY TREATMENT?
o Antibiotics daily (to prevent bacteria from developing)
o Physiotherapy to remove tough mucus from the airways through certain movements, etc. o Airway clearance (e.g., aerosol) (2x daily)
TREATMENT IN SEVERE CASES?
o lung transplant, artificial respiration, ...
o Due to chronic, progressive (destruction lungs irreversible) course it often leads to lung failure, earlier death
72
How do we diagnose cystic fibrosis?
Neonatal (newborn) screening
1. Genetic test – only for 2 most common mutations & for multiple other dangerous diseases, not just CF.
2. Sweat test – electrical stimulation of sweat glands – detects raised sweat chloride concentration.
Follow-up
o Clinical follow up to determine how far CF has evolved.
o Spirometry = measures the amount you can inhale & rate of exhalation
(The slower the rate of exhalation & volume – the more evolved)
o CT scan and X-rays to determine development of CF.
o Sputum samples (examines saliva)
73
Discuss treatment for cystic fibrosis
1. Mucolytic medication – breaks mucus layer down
2.Techniques to excrete mucus from lungs (either with machines or without)
3. Antibiotics
4.Lung transplant
Evolution in treatments – more modern – gene therapy
o Previously mainly symptomatic treatment – now proactive avoidance of development by intervention at genetic/cellular level.
o Gene replacement/ protein produced by gene replacement.
o Modulations ion channel
74
What does the CTFR gene do
The gene codes for an epithelial chloride channel
it handles the transport of chloride ions out of the cell
75
What happens in a mutant CTFR channel?
chloride ions can't elave the cell, causing a sticky mucus to build up on the outside of the cell
- causing a slimy "situation" in all organs, and being a perfect breeding environment for bacteria to grow
76
what are the percentage rates of the first symptoms
Chronic or recurrent respiratory infections = 50%
Weight stagnation = 40%
A lot of crying and always hungry
Steatorrhea (fatty diarrhoea) – fat that couldn’t be absorbed = 30%
Meconium ileus = 10%
Signs of malabsorption < 5%
77
pancreas enzyme treatment are given with every meal, what are the called?
creons
78
polyurea
excessive peeing
79
What's the incidence rate of TYPE 1 diabetes in north europe
2/1000
its been increasing over the past years
80
what's hypoglycemia and what are the symptoms
not enough sugar in blood
= most dangerous compared to hyperglycemia
= mood swings, headache, pale, tired, hungry, trembling, dizzy, sweating, poor vision
81
# W
WHat's hyperglycemia and what are the symptoms
too much sugar in blood
= drowsy, urinating, tired, thirsty, dry tongue.
82
meconium ilius
a bowel obstruction that occurs when the meconium in the child’s intestine is even thicker and stickier than normal meconium, creating a blockage in a part of the small intestine called the ileum.
83
meconium
the early stool passed by a new-born soon after birth
84
Steatorrhea
= fatty diarrhoea - fat that couldn’t be absorbed
85
what's (possible) treatment of cystic fibrosis in relation to the endocrine function of the pancreas
- Pancreas enzyme supplements with every meal - Calorie - rich, fat rich meals
- Vitamin supplements ADEK
86
secondary enuresis
temporary bedwetting
87
Ketoacidosis
ketones (breakdown product glucose) are acidic, causing body to become more acidic – dangerous.
88
Spirometry
measures the amount you can inhale & rate of exhalation
(The slower the rate of exhalation & volume – the more evolved the cystic fibrosis)
89
inflammation ..... infection
IS NOT
90
What are the two major forms of IBD
1. Crohn’s disease
2. Ulcerative colitis
91
epidemiology of IBD
o Peak between the ages of 15-30 and second peak between the ages of 60-80.
oMore frequent in“rich” countries/places such as north America, Scandinavia, andEurope.
92
Where does UC begin
Colon and rectum
93
Where does CD begin
Any part of the GI tract
94
describe the development of UC
Continuous pattern of inflammation
95
describe the development of CD
Skips lesions
96
describe the onset of UC
Acute (sudden/rapid) onset
97
describe the onset of CD
Gradual onset
98
What happens within patients with UC
»Ulcers, ulcerations, (pseudo)polyps, bulges in mucosa
»Normal architecture damaged
»Microbiome affected.
» BLOOD IN STOOL
»Can cause colon cancer
99
What happens within patients with CD
» Entire intestinal wall affected.
» Granulomas (inflammations)
» Thicker wall, smaller lumen
» Cobble stones
» Perforations – stool leaks into abdominal cavity
100
What are the symptoms of UC
» Rectal bleeding
» Having to go to the toilet very often
» Loose stools
» Abdominal pain on the lower left side
»Tenesmus: urge to defecate
» Blood in stool
101
WHat are the symptoms of CD
» Chronic and nocturnal diarhhea OR constipated
» Pain in lower right abdomen
» Weight loss
» Mild fever
» Increases in severity with age = progressive disease
» absecces and fistulae
102
What are the extra intestinal symptoms of UC
»Joint pain
»Canker sore(aften) in mouth
»Spinal deformation due to inflammation
»Slow healing wounds
»Erythema nodosum
»Eye bleeding
103
WHat are the extra-intestinal symptoms of CD
» Inflammated joints
» Same as ulcerative colitis
» Kidney problems
» Galstones
» Liver problems
104
Crohn’s disease clinical features
(1) Inflammation -> small intestine (abdominal pain, diarrhea, and fever) & large intestine (diarrhea, blood loss, weight loss and fever)
(2) Stricturing -> Bowel obstructions due to wall thickening
(3) Penetration -> abscesses and fistulae (abnormal passages get formed)
105
describe the pathogenesis of IBD
1. Genetic susceptibility: some kind of genetic predisposition – variants that cause an exaggerated inflammatory response.
2. Immune response: the overreactive immune response – people with IBD react worse to inflammations.
3. Environmental triggers: we see that IBD is more common inn wealthy countries so environmental factors do play a role HOWEVER we’re not really sure which ones.
4. Microbiome (more recently added): the collection of all bacteria that live inside our intestines – people with IBD have distinctively different microbiomes than their family members without IBD.
106
Risk factors that can cause IBD
» Diet
» Infection – if people with a genetic predisposition get certain infections, their body will react with an exaggerated inflammatory
response = the start of IBD
o Crohn’s – mycobacterium paratuberculosis
o Ulcerative colitis - after episodes of infective diarrhea
» Appendectomy (ONLY UC)
» Stress – stress triggers a relapse of IBD (NOT THE CAUSE BUT CAN TRIGGER RELAPSE)
107
What actually happens within the body during the overreactive immune response? (IBD)
= it’s an abnormal reaction of the T-cells that cause an exaggerated inflammatory response
o (Causative agents+luminal factors+modifying factors)–cause an inflammation.
But HOW?
o Lymphatic T-cells get sent to the affected zone.
o These T-cells cause the exaggerated inflammatory response.
o If the response is not transmural then it’s UC, if it is then it’s Crohn’s disease.
108
Explain the diagnosis of IBD
1. Blood tests – check for c-reactive protein which gets released in blood during an inflammatory reaction
2. Stool studies
3. Colonoscopy (=most frequently done) and endoscopy
a. Ileo-colonoscopy with biopsies (sometimes with small intestine as well)
b. Upper endoscopy with biopsies
(Capsule endoscopy - capsule with camera = still in development)
109
Explain the treatment of IBD
= the main goal of the treatment is to minimize the intestinal inflammation + improve general health + repair/heal the mucosa
Pharmacological management
o Anti-inflammatory agents: 5-amino salicylic acid (5-ASA)
o Steroids, cortisone they suppress the immune system HOWEVER can only be given for acertain number of days.
o Anti-tumor necrosis factor(anti-TNF) agents–TNF is a protein in your body that causes inflammation (everything that can be given ends with ...mab)
o Probiotics – they strengthen the microbiome daily.
110
Is UC transmural or not
no, NOT transmural
111
Is CD transmural or not
yes, transmural
112
Tenesmus
urge to defecate
113
abscesses
localized collections of pus that result from an infection
114
fistulae
abnormal connections or tunnels that form between two organs or between an organ and the outside of the body
- the transmural inflammation can lead to the formation of fistulae
115
Erythema nodosum
red spots on legs
116
explain the role of appendectomy in UC
people that get an appendectomy are less likely to develop UC, and people who developed UC after appendectomy were less likely to develop recurrent disease. = less severe course
117
What are the causes of tuberous sclerosis
1. Genetic inheritance (autosomal dominant); majority of cases
2. De-novo mutation; minority of cases
118
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.
119
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, ...
120
Explain how TSC symtpoms can affect cognitive abilities
o Mental retardation
o Social communicative, language, attention, executive functions,memory
o Fine motor problems
121
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.
122
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.
123
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.
124
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.
125
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
126
What are the different types of epilepsies in TSC
1. Epileptic spasms/Infantile spasms (West Syndrome)
2. Focal epilepsy
3. Symptomatic generalized epilepsy (Lennox Gastaut epilepsy)
127
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)
128
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!
129
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.
130
what does de-novo mutation mean
Fertilization mutations, in child itself
131
what are the 2 most common mutations of TSC
o Chromosome 9, TSC1 gene
o Chromosome 16, TSC2 gene (MORE SERIOUS)
132
what;s the incidence rate of TSC
1/6000
133
Without inhibition by the TSC complex ....
... mTOR activity remains unchecked, leading to excessive protein synthesis and cell growth. This can result in abnormal tissue growth and the formation of tumors, which is characteristic of TSC.
134
fibromas
benign growths on nails
135
Epileptic spasms/ infantile spasms (West syndrome)
The seizures look like a sudden bending forward of the body with stiffening of the arms and legs for one or two seconds – They often happen in many clusters, with hundreds of seizures a day.
136
Focal epilepsy
They are characterized by seizures arising from a specific part (lobe) of the brain.
137
Symptomatic generalised epilepsy (Lennos Gastaut epilepsy)
A type of epilepsy with multiple different types of seizures, particularly tonic (stiffening) and atonic (drop) seizures.
o Difficult to treat, especially with TSC patients.
138
discuss mtor inhibitors as treatment against TSC
they inhibit mTOR pathways, the tubers become smaller and epilepsy decreases
