Genetics Flashcards
Why are people referred to genetics?
- Family history genetic condition in relatives
- Diagnosis of genetic conditions (known / unknown)
- Management of genetic conditions
- Genetic counselling
What do people need to know before undergoing a genetic test?
- What test is for / what’s the point in having it done?
- How likely is it to be positive
- What happens if its positive
- What if its negative
- What if false positive / false negative
- Implications for other family members of positive results
- DNA stored
What types of pregnancy testing/screening are there?
- Targetted
- Whole population
When may someone undergo genetic screening?
- Antenatal
- Neonatal
- Child
- Adult
- Pre-pregnancy
- In maturity
What types of genetic testing is available in relation to reproducing?
- Test at birth
- Chorionic villus sampling
- Amniocentesis
- Pre-implantation genetic diagnosis
- Adoption
- Gamete donation
- Non invasive prenatal testing
When can non invasive prenatal testing be performed?
Around week 10
What is the inheritance of Duchenne muscular dystrophy?
X-linked
What types of genetic testing are associated with Ducehnne muscular dystrophy?
- Carrier testing
- Prenatal diagnosis
- Pre-implantation diagnosis
What are the features of autosomal dominant inheritance?
- Each child has 50% chance of inheriting mutation
- No skipped generations
- Equally trasmitted
How is Down syndrome screened for?
- Maternal age
- Triple screening
- CUBS screening
- Selection for amniocentesis
- Free fetal DNA
Give examples of common recessive disorders that raise screening issues.
- N. Europe Cystic Fibrosis
- Africans Sickle Cell DiseaseS
- Mediterranean, Asia Thalassaemias
- Ashkenazi Jews Tay-Sachs disease
- CF W1282X
- Breast / ovarian cancer BRCA1
What targeted carrier testing is available in the UK?
- CF mutation analysis 80-90% sensitive
- Haemoglobinopathy MCV, Hb electrophoresis , sickledex
- Tay Sachs enzyme activity
What is CF caused by?
Defect of cellular chloride transport
How is CF diagnosed?
- Immunoreactive trypsin (first 6 weeks)
- Sweat test
- Genotyping
How can CF present?
- Lung infections
- Meconium ileus
- Pancreatic insufficiency
What is the prevalence of CF?
1 in 2,500
What is sickle cell disorder caused by?
Abnormal Hb gene
What does sickling cause?
- Pain+++
- Cold, dehydration, infections
- Jaundice, stroke, leg ulcers, eyes, kidneys
- Anaesthetic issues
What is Tay Sachs disease
Progressive, genetic, lysosomal storage disease.
What is the cause of Tay Sachs disease?
Hexosaminidase A (hex-A) deficiency results in the build up of lipid GM(2) ganglioside, esp. in nerve cells in the brain.
How does Tay Sachs disease present?
- Baby usually develops normally until about 6 months of age.
- Progressive neurological deterioration.
- Usually fatal by 3-5 years.
What is the epidemiology of Tay Sachs disease?
- 1in 25 Ashkenazi Jews are carriers
- 1 in 250 of the general population are carriers.
What is involved in new-born screening?
- Clinical examination
- hearing
- Blood spot
Why do we screen babies?
- To enable early detection of pre-symptomatic babies
- To enable early treatment to improve health
- To reduce anxiety caused by uncertainty over symptoms before clinical diagnosis is made
What do we screen for in new-borns?
- PKU
- Congenital hypothyroidism
- Sickle cell disease
- Medium chain acyl CoA dehydrogenase deficiency
- CF
- Homocysteinuria
- Isovaleric acidaemia
- Maple syrup urine disease
- Glutaric aciduria type 1
What is the prevalence of PKU?
Affects approximately 1 in 10,000 babies in UK (ie about 80 born each year)
What is the inheritance of PKU?
Recessive (biochemical screen, carriers not identified)
What is PKU?
Babies with the condition are unable to break down phenylalanine (amino acid)
When should PKU treatment start?
By 21 days
How does PKU present?
- Untreated babies develop serious, irreversible, mental disability
- Early treatment with a strictly controlled diet prevents disability
What is the epidemiology of congenital hypothyroidism?
- 1 in 4,000 babies UK
- 1 in 10 cases inherited – hormone test
When should treatment for congenital hypothyroidism start?
By 21 days
How does congenital hypothyroidism present?
- Untreated babies -> serious, permanent, physical and mental disability
- Early treatment with thyroxine tablets prevents disability
What is the problem in congenital hypothyroidism?
Baby does not have enough thyroxine
What is the epidemiology of MCADD?
1 in 10,000-20,000 UK babies
What is the inheritance of MCADD?
Recessive (carriers not identified)
What is the problem in MCADD?
Babies with MCADD cannot easily break down fat to make energy for the body
How do babies with MCADD present?
- Serious life-threatening symptoms can occur quickly in babies not feeding well or unwell
- Mean age at first presentation is14 months.
- 25% mortality rate
What is the treatment for MCADD?
- Treatment to prevent metabolic crisis: avoid fasting and monitor frequency of meals
- Emergency regime: glucose polymer (maxijul) and IV dextrose
