Genetics Flashcards
List 10 scenarios that you should consider a congenital/genetic disorder.
1) Family history of congenital abnormality
2) Advanced maternal/paternal age
3) Dysmorphic features
4) Detection of abnormality antenatally (omphalocoele in Beckwith-Wiedeman)
5) chromosomal abnormalities and balanced translocations in parents with recurrent miscarriages
6) Multiple congenital abnormalities
7) Unexplained neurodevelopmental delay and intellectual disability
8) Autosomal recessive conditions in consanguinity
9) Certain ethnic groups
10) Family Hx of cancer
11) Ambiguous genitalia eg congenital adrenal hyperplasia
What questions need to be answered in your approach to a congenital/genetic condition?
1) What is it? Diagnosis
2) What is the cause?
3) what does it mean for the individual and the parents?
4) What is the recurrence risk?
5) Can it be prevented?
How do you decide what dysmorphism it is?
Full family Hx and family tree with 3 generations at least
Full clinical exam with emphasis on dysmorphic features and congenital defects
Requesting special investigations targeted at your suspected diagnosis
>non-specific tests = X-rays for skeletal
>specific genetic tests
How do you determine what the cause of this genetic abnormality is?
If specific diagnosis is not obvious -> classify abnormality according to pathogenic process:
>malformation (can be genetic or not)
>deformation (not genetic)
>dysplasia (always genetic)
>Disruption (not genetic)
Classify the causes of genetic abnormalities.
1) Preconception
> chromosome abnormalities (eg DS)
>Single gene defect (achondroplasia)
>multi factorial (eg cleft lip/palate, congenital heart lesions, neural tube defect)
2) Post conception
>teratogen (FAS)
>fetal constraint (eg amniotic bands)
What do you manage a child with genetic syndrome?
Multidisciplinary Team with regular follow ups
Specific guidelines for each syndrome
Information on support groups
How do you answer the question “When will it happen again?”
Recurrence risk
1) DS = 1% in non-disjunction type (different for translocation.)
2) Autosomal recessive = 25% chance
3) Autosomal dominant = 50%
4) Multifactoral conditions = 2-4% but depends on severity of condition, no of individuals in family who are affected, relation to affected person, sex of child
5) Teratogens = no risk if teratogen avoided
How can the syndromes be prevented?
Primary
>before pregnancy eg take folate 1month before becoming pregnant
>family planning
> improve maternal health and nutrition
Secondary prevention
>antenatal screening and diagnosis
>offer therapeutic options including termination of pregnancy
>non-directive counselling
Tertiary prevention
>maximise potential child with congenital disorder has
>”best possible care” including palliation
What is the purpose of genetic testing?
> diagnostic
prenatal (detect abnormality prenatally)
pre-symptomatic(test healthy person to see if they will develop eg Huntingtons disease)
predictive (eg risk of getting breast cancer)
What is important before you do a genetic test?
Pre-test counselling
What are the different chromosomal genetic tests that exist?
Chromosome testing:
>Karyotyping
>FISH
DNA testing:
>QF-PCR
>MLPA
>Chromosomal microassay analysis
What is quantitative fluorescent PCR used to test?
Trisomys
Not possible to detect mosaicism/translocation (but cheaper)
What is Array-CGH used to test for?
It is a detailed chromosome analysis. It compared the tested DNaa to a normal person.
What are the c,initial features of Down syndrome?
Hypotonia
Mental retardation
Brachycephaly
Flat facial profile
Up-slanting eyes
Epicanthic folds
Flat nasal bridge
Small and low set ears
Protruding tongue
Short stature
Brachydactyly
5th finger clinodactyly
Single palmar crease
Sandal gap
Congenital heart defect
Duodenal atresia
What is genetic counselling?
An educational process that seeks to assist affected and/or at risk individuals to understand the nature of the genetic disorder, it’s transmission and the options open to them in the management and family planning.
