Genetics Flashcards
when can congenital disorders occur
they are abnormalities that can be present at birth or manifest later in life
what percentage of children have congenital abnormalities
about 6%
what is the percentage of under 5 mortality rate is due to congenital disorders
24%
in which countries is the prevalence of neural tube defects higher
low to middle income countries
how many people have spina bifida
about 7 million
what is the commonest birth defect involving the of the CNS
spina bifida
what factors are responsible for causing neural tube defects and congenital disorders
Genetic and Environmental
what type of genetic pattern is associated with neural tube defects and congenital disorders
multifactorial pattern
what chromosomal abnormalities can cause neural tube defects
trisomy 18 (Edward syndrome)
trisomy 13 ( Patau syndrome)
triploidy
microdeletion
duplication
what single gene disorders can cause NTD
Currarino syndrome and Meckel Gruber syndrome
what is the difference between nature and nurture
nature refers to genetic association
nurture refers takes into account external factors
what types of twins do we have
Monozygotic and Dizygotic
what are concordant traits
both members of a twin pair share a trait
what is a Discordant trait
a twin pair does not share a trait
what happens in adoption studies
they separate genetics and environment, this can involve growing each member of a twin pair at two different locations that have a completely different environment
what is heritability
it refers to a trait or disease is the proportion of the total variance that is genetic
what genes are related to folate metabolism
MHTFR 667 C->T
the relevance to south africa is limited by clinical utility
what genetic factors are related to NTD
Epigenetic factors
folate metabolism genes
twin concordance
other metabolic genes
genes related to neural tube development
what genes are related to neural tube development
genes of planar cell polarization
SHH - involved in neural tube bending
genes related to cytoskeleton
genes related to cell survival
what does epigenetics refer to?
mitotically heritable changes in gene expression that occur without changes in DNA sequence
what environmental factors are involved in NTD
seasonal variations
geographical variations (Transkie rate is higher than cape town)
nutrition
twins
what factors are teratogenic and lead to NTD
- insulin dependent DM - the risk ration increases by 11 for congenital disorders
- Anticonvulsants such as sodium valproate and carbamazepine
- folate antagonists such as methotrexate ( but not at low dose)
- ARVs (Dolutegrovir had initial concerns but now they dont think it has an association)
- Alcohol
what are the prevention measures that can be taken
- improve health, nutrition and antenatal care
- family planning and spacing
- detect any current disease and treat/manage it before conception
- genetic counselling
- avoid teratogens such as alcohol, drugs and medication
what is the dose of preconceptual folate supplementation
- 0.4 mg daily
- 4 mg daily for those at high risk and this include:
women whom the previous child has a NTD - 1st degree relative with NTD
- parent with NTD
- potential teratogen risk
