Down's syndrome Flashcards
Name the three different ways down’s syndrome can arise
Chromosomal mosaic, translocational, trisomy 21
Outline trisomy 21
Non disjunction error in cell division that leads to gametes formed with one more or one less chromosome. Gamete with one more chromosome eventually leads to embryo formed with three copies of chromosome 21.
Most common type of Down’s
Outline translocational Down’s
Accounts for 3.7% (Kusre, 2015)
Robertsonian translocation: can be inherited (balanced carrier parent) or de novo.
Whole arm exchange between short arms of acrocentric chromosomes. Trisomy occurs when there are 3 copies of one chromosome (DS=21) and 2 of the other (most common with Ds is 14).
Outline chromosomal mosaic Down’s
Accounts for 2% (Paprassilion 2009)
Euploid zygote undergoes non-disjunctional event (has euploid cells that will go on to proliferate normally). New cell line created with trisomic cell and cell with one less copy. Cell with only one copy cannot proliferate, whereas trisomic succeed.
Separate cell lines created.
State physical phenotype of trisomy 21
Short stature, flattened features (causes tongue to protrude), palmer crease, fertility problems, hypothyroidism and congenital heart defects
Describe fertility problems associated with trisomy 21
Only 3 cases of spontaneous conception of down men described in literature. due to:
Partial gonadal dysfunction
Impaired spermatogenesis (aneuploid gametes destroyed - possibly, or failure with meiosis)
After puberty testicular volume falls, production of gonadotropins rises and worsens with age.
Women less problems but undergo premature menopause
State social phenotype of people with trisomy 21, give reason why
Infants with Down’s perform similarly in recognition tasks and mental age. As get older emotional recognition scores worse (Moore, 2002).
Abnormalities arise from direct overexpression of ch21 genes or compensatory mechanisms in response to abnormalities. Accumulation of secondary defects mean that initially mild defects become severe with age.
State intellectual phenotype of people with trisomy 21
Mild to moderate intellectual disability.
Early onset Alzheimer’s at age 40 (PAPER).
Outline how phenotype of translocational differs to trisomy 21
Phenotype is the same
Outline how phenotype of chromosomal mosaic differs to trisomy 21
Individuals have varied phenotype and can present as having no defect or close to trisomy 12 (spectrum).
Individuals with mosaicism shown to have significantly higher IQs at 67 compared to 57 (Paprassilion 2009).
State 4 ways that Down’s syndrome is diagnosed.
1) Chorionic villus sampling: placental cell samples.
2) Amniocentesis: amniotic fluid samples.
3) PUBS: Percutaneous Umbilical Blood Sampling, most expensive and invasive so final test.
4) After birth: characteristic features seen and chromosomal karyotype confirms
What is the link between age of mum and Down’s?
Hormonal imbalances causes comprimised microcirculation in perifollicular capillary bed (Sotonica, 2016)
Why did life expectancy of Down’s use to be so low?
Used to be ~11yrs due to congenital heart disease that occurs in up to 63% of DS and is still the leading cause of death up to 2 years (Saana, 2016).
Improvements in medicine have led to significant Life expectancy increase (now over 60+ yrs).
Why is there such a high association of congenital heart disease DS?
Thought to be due to overexpression of DSCAM (Down Syndrome Cell Adhesion Molecule) which causes epithelial mesenchymal cells to proliferate abnormally.
Describe how cerebellum is effected in DS.
Guidi et al., 2011:
Human fetus: found decreased cerebellum volume, immature cerebellum pattern and cell density compared to normal controls.
Ki 67 used as marker of cell cycling, discovered that cell proliferation is impaired. This impaired proliferation leads to decreased size and hypopolarity.
