Genetics, Neuroscience, and Imaging Flashcards
What percentage of children with ASD have a co-morbid genetic disorder?
15%
What genetic syndrome has the highest rate of co-morbid Autism?
Tuberous Sclerosis (25-50%)
What is the inheritance pattern of tuberous sclerosis and what are its signs?
1) Autosomal dominant
2) Benign tumors throughout body, ashleaf spots (HYPOpigmented macules), shagreen patches (thick, leathery skin patch usually on the lower back). Also has a facial rash
What is the most common INHERITED cause of intellectual disability?
Fragile X syndrome
What is the most common CHROMOSOMAL cause of intellectual disability?
Down syndrome
What is the most common autosomal trisomy?
Down syndrome
What is the rate limiting step in serotonin synthesis?
Tryptophan hydroxylase
What gene is showing evidence of linkage to OCD?
Gain of function polymorphisms in the SLC6A4 promoter
What is the preferred imaging modality to localize seizure foci when considering surgery for medically intractable seizures (and why)?
PET scan (able to show interictal hyPOmetabolism around seizure foci)
What are MRI brain findings of individuals with ASD? What about postmortem studies? What about early growth and development? What about neurochemical differences?
1) Larger brains and abberations in white matter tract development
2) Limbic system abnormalities
3) Decreased formation of purkinje cells in the cerbellum AND accelerated head growth during infancy
4) Abnormalities in serotonin synthesis
What are examples of neuropeptide neurotransmitters?
Hyopthalamic releasing factors (somatostatin, GnRH), pituitary hormones (GH, TSH), opiate peptides (endorphins, enkephalins), neurohypophyseal peptides (oxytocin, vasopressin), neuronal (ANF, VIP), GI/brain/pancreas peptides (CCK, glucagon, gastrin), endocrine (insulin, PTH, calcitonin), circulating (angiotensin, bradykinin)
What are some examples of conventional (small-molecule) neurotransmitters?
Serotonin, dopamine, norepinephrine, GABA, glycine
What are features of neurofribromatosis type-1?
– Café-au-lait spots (large, hyperpigmented skin patches)
- Cutaneous neurofibromas, optic gliomas, and PHEOCHROMOCYTOMAS
- Cognitive difficulties
- Seizures
- Yellow, dome-shaped growths on the iris (iris hamartomas –> Lish nodules)
What gene has been linked to the development of depression in those with stressful life events and childhood maltreatment?
BDNF
What gene has been proposed to lead to development in PTSD in those with history of childhood maltreatment?
FKBP5
Advanced paternal age is associated with increased risk for what?
Sporadic (non-familial) schizophrenia
What is the best imaging modality to assess for a TBI?
Diffusion Tensor Imaging (DTI)
1) What syndrome dramatically increases the risk of developing schizophrenia more than any other genetic illness? 2) How high is the risk? 3) What chromosome is it associated with?
1) Velocardiofacial syndrome (also know as DiGeorge Syndrome or 22q11.2 deletion syndrom)
2) Up to 20x increased risk
3) Deletion on chromosome 22
What are the symptoms of Velocardiofacial syndrome?
CATCH-22
- Cardiac abnormalities
- Abnormal facies
- Thymic aplasia
- Cleft palate
- Hypocalcemia and Hypothyroidism
- 22: Deletion of chromosome 22
(remember - Velocardiofacial syndrome is the new name for DiGeorge syndrome or 22q11.2 deletion syndrome)
1) What does magnetic resonance spectroscopy (MRS) measure? 2) What do you use MRS to evaluate?
1) Uses the signal from hydrogen protons to measure biochemical concentrations of brain metabolites
2) Differentiate between brain tumor types. Evaluation of degenerative disorders, HIV, radiation injury, encephalopathy, and ischemia
1) What is the heritability pattern of Lesch-Nyhan syndrome? 2) What is the deficiency? 3) How does it present?
1) X-linked recessive
2) Disorder of purine and pyrimidine metabolism (deficiency in hypoxanthine-guanine phosphoribosyl transferase –> leading to HYPERURICEMIA)
3) CHOREOATHETOSIS, hyperreflexia, hypertonia, dysarthria, behavioral disturbances (AGITATION), cognitive impairment, SELF-MUTILATORY (biting) BEHAVIOR
What is the mutation that causes NF1 (chromosomal location, gene name, and what the gene encodes for)?
Chromosome 17, mutation of NF1 tumor suppressor gene, encodes for Ras GTPase activating protein neurofibrin
What is the mutation that causes NF2 (chromosomal location, gene name, and what the gene encodes for)?
Chromosome 22, mutation of NF2 gene, encodes for merlin/schwannomin protein
What are the genes suspected to play a role in ADHD (4)?
COMT (Catecholomine-O-methyl transferase)
SLC6A3 (a dopamine transporter)
DRD4 (Dopamine D4 receptor)
SNAP-25 (synaptosomal-associated protein)
