Genetics

Question 1

Why are people referred to genetics?

Answer 1

• Family history genetic condition in relatives
• Diagnosis of genetic conditions (known / unknown)
• Management of genetic conditions
• Genetic counselling

Question 2

What do people need to know before undergoing a genetic test?

Answer 2

• 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

Question 3

What types of pregnancy testing/screening are there?

Answer 3

• Targetted

- Whole population

Question 4

When may someone undergo genetic screening?

Answer 4

• Antenatal
• Neonatal
• Child
• Adult
• Pre-pregnancy
• In maturity

Question 5

What types of genetic testing is available in relation to reproducing?

Answer 5

• Test at birth
• Chorionic villus sampling
• Amniocentesis
• Pre-implantation genetic diagnosis
• Adoption
• Gamete donation
• Non invasive prenatal testing

Question 6

When can non invasive prenatal testing be performed?

Answer 6

Around week 10

Question 7

What is the inheritance of Duchenne muscular dystrophy?

Answer 7

X-linked

Question 8

What types of genetic testing are associated with Ducehnne muscular dystrophy?

Answer 8

• Carrier testing
• Prenatal diagnosis
• Pre-implantation diagnosis

Question 9

What are the features of autosomal dominant inheritance?

Answer 9

• Each child has 50% chance of inheriting mutation
• No skipped generations
• Equally trasmitted

Question 10

How is Down syndrome screened for?

Answer 10

• Maternal age
• Triple screening
• CUBS screening
• Selection for amniocentesis
• Free fetal DNA

Question 11

Give examples of common recessive disorders that raise screening issues.

Answer 11

• N. Europe Cystic Fibrosis
• Africans Sickle Cell DiseaseS
• Mediterranean, Asia Thalassaemias
• Ashkenazi Jews Tay-Sachs disease
• CF W1282X
• Breast / ovarian cancer BRCA1

Question 12

What targeted carrier testing is available in the UK?

Answer 12

• CF mutation analysis 80-90% sensitive
• Haemoglobinopathy MCV, Hb electrophoresis , sickledex
• Tay Sachs enzyme activity

Question 13

What is CF caused by?

Answer 13

Defect of cellular chloride transport

Question 14

How is CF diagnosed?

Answer 14

• Immunoreactive trypsin (first 6 weeks)
• Sweat test
• Genotyping

Question 15

How can CF present?

Answer 15

• Lung infections
• Meconium ileus
• Pancreatic insufficiency

Question 16

What is the prevalence of CF?

Answer 16

1 in 2,500

Question 17

What is sickle cell disorder caused by?

Answer 17

Abnormal Hb gene

Question 18

What does sickling cause?

Answer 18

• Pain+++
• Cold, dehydration, infections
• Jaundice, stroke, leg ulcers, eyes, kidneys
• Anaesthetic issues

Question 19

What is Tay Sachs disease

Answer 19

Progressive, genetic, lysosomal storage disease.

Question 20

What is the cause of Tay Sachs disease?

Answer 20

Hexosaminidase A (hex-A) deficiency results in the build up of lipid GM(2) ganglioside, esp. in nerve cells in the brain.

Question 21

How does Tay Sachs disease present?

Answer 21

• Baby usually develops normally until about 6 months of age.
• Progressive neurological deterioration.
• Usually fatal by 3-5 years.

Question 22

What is the epidemiology of Tay Sachs disease?

Answer 22

• 1in 25 Ashkenazi Jews are carriers

- 1 in 250 of the general population are carriers.

Question 23

What is involved in new-born screening?

Answer 23

• Clinical examination
• hearing
• Blood spot

Question 24

Why do we screen babies?

Answer 24

• 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

Question 25

What do we screen for in new-borns?

Answer 25

- PKU - Congenital hypothyroidism - Sickle cell disease - Medium chain acyl CoA dehydrogenase deficiency - CF - Homocysteinuria - Isovaleric acidaemia - Maple syrup urine disease - Glutaric aciduria type 1

Question 26

What is the prevalence of PKU?

Answer 26

Affects approximately 1 in 10,000 babies in UK (ie about 80 born each year)

Question 27

What is the inheritance of PKU?

Answer 27

Recessive (biochemical screen, carriers not identified)

Question 28

What is PKU?

Answer 28

Babies with the condition are unable to break down phenylalanine (amino acid)

Question 29

When should PKU treatment start?

Answer 29

By 21 days

Question 30

How does PKU present?

Answer 30

- Untreated babies develop serious, irreversible, mental disability - Early treatment with a strictly controlled diet prevents disability

Question 31

What is the epidemiology of congenital hypothyroidism?

Answer 31

- 1 in 4,000 babies UK | - 1 in 10 cases inherited – hormone test

Question 32

When should treatment for congenital hypothyroidism start?

Answer 32

By 21 days

Question 33

How does congenital hypothyroidism present?

Answer 33

- Untreated babies -> serious, permanent, physical and mental disability - Early treatment with thyroxine tablets prevents disability

Question 34

What is the problem in congenital hypothyroidism?

Answer 34

Baby does not have enough thyroxine

Question 35

What is the epidemiology of MCADD?

Answer 35

1 in 10,000-20,000 UK babies

Question 36

What is the inheritance of MCADD?

Answer 36

Recessive (carriers not identified)

Question 37

What is the problem in MCADD?

Answer 37

Babies with MCADD cannot easily break down fat to make energy for the body

Question 38

How do babies with MCADD present?

Answer 38

- Serious life-threatening symptoms can occur quickly in babies not feeding well or unwell - Mean age at first presentation is14 months. - 25% mortality rate

Question 39

What is the treatment for MCADD?

Answer 39

- Treatment to prevent metabolic crisis: avoid fasting and monitor frequency of meals - Emergency regime: glucose polymer (maxijul) and IV dextrose