Week 9 Flashcards

Question

What happens in pre eclampsia

Answer 1

Vasospasm Increased BP, headaches Reduced organ perfusion Coagulation Kidneys: reduced urine output, proteinuria, hyperuricemia Liver: raised liver enzymes, liver capsule stretch Placenta: IUGR, abruption, fetal death Brain: occipital lobe, ischaemia, convulsions

Answer 2

Antihypertensives eg labetalol, nifedipine, methyldopa, hydralazine Fluid restrict (85mls/hour) Magnesium sulphate to prevent and treat seizures Delivery- balance between achieving best outcomes for mother and fetus

Answer 3

Important issue in pregnancy Requires MDT care in combined clinic Pre-existing type 1 or type 2 Gestational diabetes DM affects all systems in body- actual or effective insulin deficiency 3-4 per 1000 pregnancies Before insulin 40% women died during pregnancy Remainder died within 2 years of delivery Fetal loss rate >50% With insulin maternal mortality fell to 2-3% Now deaths very rare Fetal loss rates remained high Initially concentrated on reducing stillbirth but PNMR high Optimisation of maternal control and fetal surveillance lead to PNMR close to non diabetic

Answer 4

Poverty Illiteracy Population explosion Low socioeconomic Status Poor health facilities Poor social status of woman Lack of political will

Answer 5

Stop bleeding Stop infection Training Transport

Answer 6

The correct number of genes working correctly to give the correct gene dosage in the correct tissues at the correct time In a supportive intra-uterine environment

Answer 7

Humans have over 20000 protein coding genes A chromosome is made of a single molecule of DNA A specific stretch of DNA where the sequence contains genetic instructions is a gene Genes are arranged one after the other along the DNA of a chromosomes with stretches of non-coding DNA between them Each chromosome has hundreds of genes

Answer 8

Function: -reduction division (23 chromosomes per gamete) -reassortment of genes: independent segregation of chromosomes crossing over Mechanism: -each homologue replicates to give 2 chromatids -homologous pair -exchange of material between non sister chromatids. Crossing over, recombination -chiasmata (visible cytologically) are the physical manifestations of crossing over

Answer 9

DNA replication: new mutations (copying errors) Meiotic cell division: anomalies of chromosome number (non disjunction), anomalies of chromosomes structure (unequal crossing over) As the gamete contains the genetic anomaly resulting from an error in meiosis the zygote will have the anomaly in all body cells

Answer 10

Mutations in single genes Common complex/ Multifactorial diseases Chromosome imbalance causes change in gene dosage Mitochondrial disorders- generally affect organ systems with high energy requirement

Answer 11

Numerical: aneuploidy, polyploidy. Monosomy, trisomy, triploidy Structural: translocations (reciprocal, Robertsonian(centric fusion)). Deletions, duplications, inversions Different cell lines: mosaicism

Answer 12

Autosomes: -Down syndrome (trisomy 21:47, XX +21) -Edwards’s syndrome (trisomy 18:47, XX,+18) -Patau syndrome (trisomy 13:47, XX +13) Sex chromosomes: -turner syndrome 45 X -Klinefelter syndrome 47 XXY All chromosomes: -triploidy 69 chromosomes

Answer 13

Through genetic diagnosis in a relative Through the pattern of affected people in the family From the results of screening or scans in the pregnancy From the results of genetic testing in a pregnancy

Answer 14

Previous child with a single gene disorder Family history of a single gene disorder A parent with a chromosomal anomaly Parental ages

Answer 15

Build up the tree from the bottom starting with affected child and siblings. Record names, dates of birth and maiden names Choose one parent ask about siblings and their children then parents Add info other side of family Colour in symbol is person affected Sloping line through symbol if person died Ask for miscarriages, stillbirths, deaths in each partnership Children with other partners, divorce Double line joins union of consanguineous couple Diagonal line for twins with line between if identical

Answer 16

Family history of genetic disorder eg in a previous sibling Parental consanguinity Population ancestry Elevated maternal age Elevated paternal age Environmental exposure affecting DNA

Answer 17

CF is inherited in autosomal recessive manner Autosomal recessive inheritance. 1/4 affected

Answer 18

Consanguineous: where two people are related by blood ie share a common ancestor

Answer 19

Chromosome anomalies can be inherited and give distinctive patterns in the family Robertsonian translocation: centric fusion. Breakage of 2 acrocentric chromosomes (13,14, 15,21,22) at or close to their centromere with subsequent fusion of their long arms- short arms are lost Reciprocal translocation: breakage of 2 non-homologous chromosomes with exchange of fragments Multiple miscarriages, children with congential anomalies in multiple generations

Answer 20

Meiosis Fertilisation by normal gamete -normal: no risk to children -balanced carrier: normal but risk to children of having unbalanced translocation -partial trisomy and partial monosomy: miscarriage, congenital malformation, developmental delay, intellectual disability -partial monosomy and partial trisomy: miscarriage, congenital malformation, developmental delay, intellectual disability Unbalance reciprocal translocation

Answer 21

Afro-Caribbean Ashkenazi Jewish Mediterranean Northern Europe

Answer 22

Incidence of trisomy 21 at time of CVS (11 weeks) amniocentesis (16 weeks) and term Increases with maternal age

Answer 23

22 cell divisions by 5 months gestation- stock of oocytes each remains in maturation arrests until ovulation Each month one is ovulated Meiosis I completed at ovulation Meiosis II competed at fertilisation There may a lengthy interval between onset and completion of meiosis Accumulating effects on the primary oocyte may damage the cells spindle formation and repair mechanisms predisposing to non-disjunction

Answer 24

Eggs held at crossing over stage in meiosis from approx 6 months gestation So “wear and tear” with increasing maternal age in machinery for cell division thought to be major component The trisomy 21 type of Down syndrome is the result of an error in meiosis and has a recurrence risk of about 1 in 100 Trisomy 21 is the result of an error in meiosis, Meiotic non disjunction, has recurrence risk of about 1 in 100

Answer 25

The number of cell divisions required to produce a human sperm Spermatogonium every 16 days from puberty 4 spermatozoa This spermatogonium maintains the stock of spermatogonia and continues to divide New mutations increase with paternal age Higher mutation rates in males are likely to be related to the greater number of germ cell divisions (The DNA in a particular sperm is the result of hundred of rounds of replication)

Answer 26

To provide options for management of the pregnancy eg termination of pregnancy if fetus shown to be affected with severe condition To guide management in the new born period eg metabolic/endocrine conditions where immediate treatment might be needed For parents information

Answer 27

Pregnancy known to be at risk of genetic disorder (eg identified through prior family history) -no pregnancies, adoption, donor gametes -screening via imaging, targeted genetic testing invasive, targeted genetic testing, noninvasive -preimplantation genetic diagnosis PGD Pregnancy not thought to be at prior risk but affected with anomalies

Answer 28

Detects structural abnormalities Routine screening of low risk pregnancies -12 weeks dating scan -20 weeks structural anomaly scan High resolution scanning for specific disorder (eg cardiac/fetal MRI) Safe and non invasive Diagnostic limitations

Answer 29

Targeted genetic test where baby is high risk of a genetic condition -eg gene testing for CF -chromosome testing for familial translocation Have to know the genetic diagnosis in the family before being able to offer a targeted genetic test Amniocentesis may also be offered after structural abnormalities have been picked up in a pregnancy eg suspicion of Down syndrome Invasive test carries a risk of miscarriage

Answer 30

From 11 weeks gestation Under US guidance Chromosome analysis-direct or cultured cells DNA analysis- uncultured cells- result 1-2 weeks Miscarriage rate ~1% Associated with limb reduction defects if performed before 9 weeks

Answer 31

From 15 weeks gestation Under US guidance Trans-abdominal Chromosome analysis- cultured cells DNA analysis- cultured cells- results 2-3 weeks Miscarriage rate ~0.5-1% Vaginal termination

Answer 32

Blood test from the mother to diagnose a genetic condition in the fetus -free fetal DNA circulating in maternal blood -measurable from 8-9 weeks Fetal sexing- for X linked conditions eg DMD NIPT- screening test for trisomy 21,18,13 NIPD- diagnostic test for certain conditions eg DMD,SMA, CF/bespoke Earlier in pregnancy No risk miscarriage NIPT-screening not diagnostic test Not available for all conditions

Answer 33

PGD genetically testing an embryo before it is placed into the uterus that has been diagnosed as being free of a specific genetic condition Highly specialised service Involved IVF Only for licensed conditions

Answer 34

Ovarian stimulation IVF Blastomere biopsy of day 3 Genetic analysis Transfer unaffected embryo Clinically normal baby

Answer 35

2-5% pregnancies Significant mortality and morbidity Challenges: non specific, difficult to assess, limited phenotype Testing approach: rare specific tests for specific phenotypes, otherwise broad approach Stepwise genetic testing: -QF-PCR detects chromosomal aneuploidy -microarray detects copy number disorders -trio exome detects monogenic

Answer 36

Exome: coding regions of 20000 genes approx 2% genome Genome: all 3 billion base pairs Very fast turn around of exome testing in pregnancies with multiple malformations where there is: -a strong likelihood of a genetic result -the result will impact management in pregnancy Complex Demanding of resources Time sensitive Lots data to analyse Need to limit result that are directly relevant to pregnancy Life changing decisions MDT approach needed

Answer 37

Making an accurate diagnosis Describing the consequences of the disorder Advising on the probability of having an affected child Discussing the ways in which this can be treated or prevented