Obstetric genetics Flashcards
Define autosomal dominant
Heterozygotes with one copy of the abnormal gene atr affected
Define autosomal recessive
Homozygotes with two copies of the abnormal gene are affected
Define X-linked recessive
Males with one copy of the abnormal gene on the X-chromosome are affected
Features of X-linked recessive inheritance
No male-male transmission
Unaffected carrier females
All men who inherit the mutation are affected
Examples of common x-linked recessive disorders
Duchenne muscular dystrophy
Haemophilia
Red-green colour blindness
Duchenne muscular dystrophy
Most common and severe form of muscular dystrophy
Presentation at 3-5 years
1/3 have learning difficulties as well
Waddling gait
Difficulty running/climbing stairs
Gradual deterioration leading to loss of mobility
Cardiorespiratory failure eventually
Features of autosomal recessive inheritance
To develop diseases, both germ line mutations must be inherited
Equally transmitted by males and females
Common autosomal recessive disorders
Hereditary haemochromatosis
Cystic fibrosis
B-thalassaemia
Cystic fibrosis - symptoms
Progressive lung disease
Pancreatic dysfunction
Elevated sweat electrolytes
For a recessive condition with early onset, what is the chance of a patient being a carrier if they are unaffected but their sibling is
2/3
Assumptions of hardy-Weinberg principle
Large randomly mating population
Relative proportion of different genotypes remains Constant
No outside influences
2 alleles for an autosomal condition
what is the hardy Weinberg equation ?
What types of conditions is the hardy-Weinberg principle used for ?
Autosomal recessive and X-linked
What factors can disturb the hardy Weinberg principle
Non-random mating
consanguinity - relationships between close relative can increase carrier risk within a family
high mutation rate can affect the mutation-selection eqm
selection of geterozygote advantage
Describe the ultrasound scans given as routine prenatal screening
Dating scan at 8+ weeks
- identifies whether pregnancy is singleton/multiple
unchallenged translucency (NT) scan at 10-14 weeks :
- thickness of neural tube measured
feral anomaly scan at 18-20 weeks :
Causes of increased neural tube thickness
Down syndrome
major congenital heart disease
skeletal dysplasias
diaphragmatic hernias
Describe the biochemical serum screening tests
First trimester:
- 10-14 weeks gestation (done at same time at NT scan)
- accuracy dating needed to interpret results
- free beta-human chorionic gonadotropin , placenta-associated plasma protein A assessed
- high detection rate but needs sample from placenta or amniotic fluid
second trimester if women book later in pregnancy :
- alpha-feta protein
- free beta-HCG
- estriol
What conditions does an abnormal MSAFP assay indicate?
>>MSAFP levels = neural tube defect / anterior ab wall defect / risk of miscarriage / lack of growth / multiple pregnancy / congenital nephrotic syndrome
Name the non-invasive targeted tests
Ultrasound scans - surveillance/3D scans/feral echocardiogram
foetal MRI scan
molecular testing of foetal cells or DNA in maternal blood
Invasive targeted test
Chorionic villus sampling (placental sampling)
- usually carried out at 11-13 weeks
- transabdominal approach
- yields foetal DNA for molecular tests
amniocentesis (sampling of amniotic fluid):
- usually carried out at 15-16 weeks
- analysis takes several weeks ; low yield of foetal DNA
cardocentesis (foetal blood sampling )
foetal tissue biopsy - liver, muscle, skin
Polygenic inheritance
Inheritance controlled by many genes with small additive effects
genes at many different loci contribute to the phenotype
no gene is dom/rec
gradation of phenotypes
Multifactorial inheritance
Risk is higher if a child of the lower risk gender is affected
even when someone has a high genetic liability they will not be affected if the environment is favourable
Common congenital malformations
Cleft lip and palate
congenital dislocation of the hip
congenital heart defects
talipes (clubbed foot)
pyloric stenosis (obstruction of opening to the small intestine)
Adult onset disorders with multifactorial inheritance
Diabetes Mellitus (type 1)
epilepsy
glaucoma
ischaemia heart disease
rheumatoid arthritis
