Treatment development of mTOR pathway related diseases

Question 1

Tuberous Sclerosis Complex

Answer 1

• multi-system genetic disease that causes non-cancerous (benign) tumors to grow in the brain and on other vital organs such as the kidneys, heart, eyes, lungs, and skin

Symptoms
- Skin abnormalities. …
- Seizures. …
- Cognitive disabilities. …
- Behavioral problems. …
- Kidney problems. …
- Heart issues. …
- Lung problems. …
- Eye abnormalities

Question 2

DSM-5 classification of ID

Answer 2

• Onset in childhood
• Deficits in both intellectual and adaptive functioning
• Conceptual, social, and practical domains

Question 3

Under which IQ is ID inhibiting/noticeable?

Answer 3

under 70

Question 4

What makes ID clinically complex?

Answer 4

variable phenotype

Question 5

What are treatment targets and outcomes in rare genetic neurodevelopment disorders?

Answer 5

• burden to patient - identify and target meaningful intervention
• any underlying cause of ID
• aim to improve patient’s functioning and life skills
• early behavioural and cognitive interventions

Question 6

Definition Phenotype

Answer 6

• observable characteristics or traits of an organism
• determined by biological and psychosocial factors

Question 7

What makes ID clinically complex due to psychological variability?

Answer 7

• Stress
• Traumatic events
• Attachment issues
• Anxiety and mood issues over time
• Coping style
• Acceptance

Question 8

What makes ID clinically complex due to social/contextual variability?

Answer 8

• Family / system stress
• Living situation
• Socio-economic status / Finances
• Peer support
• Level of education
• Patient organization
• Compliance
• Health care system
• Access to interventions
  and information
• Culture / religion
• Chemical exposure, climate, intoxications
• Diet, physical activity, lifestyle

Question 9

What makes ID clinically complex due to biological variability?

Answer 9

• Type, site of mutation
• Loss of heterozygosity / epigenetic mechanisms / modifying
  genes / metabolic factors
• Enzyme / protein (rest) activity
• Variable expression over life
• Somatic comorbidity e.g. epilepsy, pain, motor problems, communication problems, intoxications
• Side effects medication
• Ageing

Question 10

genetic background of TSC

Answer 10

• mutations in the TSC1 or TSC2 genes –> causes over-activation of the mTOR complex
• a protein kinase that regulates protein synthesis and cell growth in response to growth factors, nutrients, energy levels, and stress
• type, position of mutation associated with intelligence and seizures
• somatic second-hit mutation required