Syndromic intellectual disability : from treatment targets to intervention Flashcards
What are DSM-V classifications of intellectual disability (ID)?
- Onset in childhood
- Deficits in both intellectual and adaptive functioning
- Conceptual, social, and practical domains
The International Classification of Functioning, Disability and Health (ICF) is the international standard for framing, describing, recording and measuring functioning and disability.
What factors are evaluated for the ICF?
All factors are evaluated in their relationship to activity.
- Health condition (health or disease)
- Participation
- Personal factors
- Environmental factors
- Body functions and structure
What is the phenotype?
The set of (variable) observable characteristics or traits of an organism, which are determined by biological and psychosocial factors.
Name biological factors that are variable.
- 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. epilesy, pain, motor problems, communication problems, intoxication
- Side effects medication
- Ageing
Name psychological factors that are variable.
- Stress
- Traumatic evets
- Attachment issues
- Anxiety and mood issues over time
- Coping style
- Acceptance
Name social or contextual factors that are variable.
- 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
What is tuberous sclerosis?
- A rare, multi-system genetic disease that causes non-cancerous (benign) tumors to grow in the brain and on other vital organs (neurocutanous/multisystem).
- The disorder has a great variability in its phenotype.
- 100% penetrance
- Mutation of TSC1 and TSC2
What is the normal function of TSC1 and -2?
TSC1 (hamartin) and TSC2 (tuberin) form a protein-complex. The complex integrates environmental signals such as energy status and growth factors into TOR signalling. In case of stress or low energy availability, it is actiavted and regulated protein synthesis down. Growth factors lead to an inhibition of the complex and have a positive effect on protein synthesis.
Defects in its genes result in less control of cell growth and may cause tuberous sclerosis (complex).
Explain why tuberous sclerosis has such a high variability in its phenotype?
The position and type of mutation is associated with intelligence and seizures.
What can you do if you know that the position and type of mutation are associated with the degree of intelligence and seizures?
By identifying the position and type of mutation of multiple patients (group level), the phenotype of the disease can be predicted.
What is loss of heterozygosity?
A common form of allelic imbalance by which a heterozygous somatic cells becomes homozygous because one of the two alleles gets lost.
What happens if there is loss of heterozygosity in patients with tuberous sclerosis?
The symptoms become more severe (if I understood correctly)
The picture depicts the criteria for clinical diagnostics of tuberous sclerosis.
Why are the diagnostic criteria not the same as the treatment targets?
Because the symptoms can vary, not only in type but also in degree. This means that patient A with tuberous sclerosis is affected the most by their skin while patient B with tuberous sclerosis is not affected by their skin, but by other (to him) more troubling symptoms. This also means that these two patients need to have different (symptomatic) treatments.
The picture depicts a variety of drugs meant for treating different symptoms of tuberous sclerosis complex.
What drug target is there for tuberous sclerosis complex?
mTOR inhibition
The International Classification of Functioning, Disability and Health (ICF) is the international standard for framing, describing, recording and measuring functioning and disability.
In this framework a variety of factors are described that are able to measure functioning and disability (see picture).
Name for components (body functions & structure, environmental and personal factors, participation, activity) that are integrated into the ICF what factors influence how tuberous sclerosis complex can affect the patient.
What are TSC-Associated Neuropsychiatric Disorders (TAND)?
A new terminology proposed to describe the interrelated functional and clinical manifestations of brain dysfunction in TSC, including aggresive behaviors, autism spectrum disorder (ASD), intellectual disabilities, psychiatric disorders, neuropsychological deficits, as well as school and occupational difficulties.
What are clinical characteristics of the brain of a tuberous sclerosis complex patient?
- Tubers (cells that fail to differentiate to functions neuronal cells during early stages of brain development)
- Nodules (small tumors)
- Sub-ependymal giant cell tumors (SEGAs) (tumor in the ventricular system)
- Microstructural white matter abnormalities
- Radial migration lines (linear bands radiating from the periventricular white matter to the subcortical region)
The radial migration lines are thought to be specific for tuberous sclerosis.
A correlation was found between the amount of radial migration lines and ….
What correlates with the amount of radial migration lines?
Intelligence
