CASE 2 Flashcards
what is genetic counselling?
the process of helping people understand and adapt to the medical, psychological and familial implications of genetic contributions to disease
what does genetic counselling involve?
- interpretation of family and medical histories to asses the chance of disease occurrence or recurrence
- education about inheritance, testing, management, prevention, resources and research
- counselling to promote informed choice and adaptation to the risk or condition
what is a recurrent miscarriage?
3 < miscarriages
risk factors of miscarriage
age, smoking, alcohol, drug use, obesity
what is a karyotype?
= a picture of someone’s chromosomes
= a complete set of metaphase chromosomes sorted by length. stain applied.
the number and visual appearance of the chromosomes in the cell nuclei of an organism or species
what are the 2 common chromosomal causes of a miscarriage?
- numerical abnormalities
2. structural abnormalities
what is non-disjunction?
failure of separation of chromosomes in meiosis 1
what is aneuploidy and where do they normally arise?
= having missing or extra chromosomes — numerical abnormality
- normally arise from errors in meiosis 1
= most common genetic cause of miscarriage and congenital birth defects
trisomy vs monosomy
- trisomy = 3 copies of a chromosome. cause 35% of miscarriages before 20 weeks pregnancy
- monosomy = 1 copy of a chromosome
what is a risk factor for trisomies?
maternal age
give examples of viable trisomies and a viable monosomy
trisomies = Patau’s Syndrome (trisomy 13), Edward’s Syndrome (trisomy 18), Down’s Syndrome (trisomy 21)
monosomy = Turner Syndrome (monosomy X)
structural abnormalities - what do they result from and key characteristics
- result from chromosome breakage
- usually involve 1 or 2 chromosomes
- can be spontaneous
- mutagenic agents increase rate
- rate also increased in certain inherited conditions with defects of DNA replication and repair
when does an unbalanced translocation occur?
when a fetus inherits a chromosome with missing or extra genetic material from a parent with a balanced translocation
what is a balanced translocation and are they common?
chromosomes not arranged in a normal pattern, common: roughly 1/500 people
when is a balanced translocation identified?
- subfertility = the failure to establish a clinical pregnancy after 12 months of regular, unprotected sexual intercourse
- raised risk from a combined test
- parental testing carried out after child is found to have unbalanced chromosomal pattern
- incidental finding antenatally from an amniocentesis
types of chromosomal translocation
- reciprocal translocation (segments from 2 different chromosomes are exchanged)
- robertsonian translocation (an entire chromosome attaches to another)
- inversion (a portion of chromosomes in opposite orientation)
why does a translocation increase the chance of a miscarriage?
when a carrier of a balanced translocation has children, the consequence is the production of eggs or sperm with incomplete or partially duplicated sets of chromosomes — results in monosomic or trisomic zygotes
what is non-invasive prenatal screening (NIPT)?
a maternal blood test (at roughly 9 weeks) to refine T21/T18/T13 risk, reducing need for invasive testing
if a fetus has Down Syndrome, what is found slightly more in maternal circulation?
chromosome-21 specific DNA
what are the 2 types of invasive antenatal testing?
- chorionic villus sampling (CVS)
2. amniocentesis
what is involved in CVS? when is it performed? complications?
- placental tissue (chorionic villi) is aspirated through the cervix (using a tube) or abdominal wall (using a needle) under ultrasound visualisation
- performed after 10 weeks gestation
- fetal cells obtained are karyotyped
- complications = heavy bleeding and miscarriage (1 in 100)
what is involved in amniocentesis? complications?
- amniotic fluid is removed and the foetal cells that it contains are analysed
- the needle inserted (through abdomen or vaginal canal) to obtain a fluid sample is guided into position using ultrasound visualisation
- only performed when there is a known risk because of potential threat to foetus/mother
- complications/drawbacks = large volume needed but such volumes may harm foetus. usually performed in weeks 14-15 but results may take several weeks to come back by which time therapeutic abortion may not be available. chance of miscarriage = 1/100
what is the one way XYY can occur?
through non-disjunction in meiosis 2
Down’s Syndrome
= the most common of the chromosomal disorders
- 95% result from non-disjunction (parents of these children have a normal karyotype) — trisomy 21 — chromosome count is 47
- approx 75% with trisomy 21 die in embryonic or foetal life
- 2% robertosonian translocation (50% familial, 50% de novo)
- 1% other chromosomal arrangement involving 21q22
structural chromosomes rearrangements
- can be spontaneous. rate increased by exposure to mutagenic agents
- can be balanced or unbalanced
- balanced: rearrangement is complete. no loss of genetic material. usually harmless. carriers often at risk of producing offspring with an unbalanced chromosomal complement
- unbalanced: chromosome complement contains an incorrect amount of chromosome material. usually has serious effects
robertsonian translocation
- results from the breakage of two acentric chromosomes at or close to their centromeres, with subsequent fusion of their long arms
- the short arms of each chromosome are lost but this is of no
clinical importance - no loss or gain of important genetic material — functionally balanced arrangement
- outcomes: normal, carrier of balanced translocation, complete trisomy of one of the involved chromosomes, complete monosomy of one of the involved chromosome = always lethal (can have a conceptus but not a child)
