83 Genetic counselling

Question 1

What is genetic counselling?

Answer 1

Process of helping people understand and adapt to the medical, psychological and familial implications of genetic contributions to disease

Question 2

What does genetic counselling integrate?

Answer 2

• Interpretation of family and medical histories to assess the chance of disease occurrence or recurrence
• Education about inheritance, testing, management, prevention, resources and research
• Counseling to promote informed choices and adaptation to the risk or condition

Question 3

What is CF?

Answer 3

• Autosomal Recessive inheritance
• Most common fatal inherited disease
in Caucasians
• Incidence of 1 in 2400 in UK
• Carrier frequency 1 in 23 (Scotland)
• Mutated chloride channel

Question 4

What is the newborn screening programme for CF?

Answer 4

• Identification of babies with CF to allow early treatment interventions
• Based on heel-prick immuno-reactive trypsinogen (IRT) level
• Raised IRT - test using CF mutation kit
• CF suspected if IRT raised and one pathogenic
mutation found
• CF confirmed if 2 pathogenic mutations found

Question 5

R117H as a mutation for CF?

Answer 5

• Mild mutation
• 2nd mutation in 1.85% of Scottish CF patients
• Makes up 9% of CF mutations identified on postnatal screen
• Majority of R117H compound heterozygotes do not present with CF in childhood
• Effect of R117H varies according to Intron 8 splice site efficiency

Question 6

What does CFTR stand for?

Answer 6

CF transmembrane conductor receptor

Question 7

Effects of CFTR Intron 8 variants

Answer 7

• Amount of normal CF protein produced depends on sequences in intron 8
• 7T most common in population
• 5T poor splicing resulting in exon 9 skipping
• R117H alone is not enough to cause CF, but effect compounded if also 5T i.e. not producing full length protein

Question 8

Poly T status: R117H/5T?

Answer 8

• 5T with R117H is a combination that favours CF
• Risk of developing symptoms of CF during
childhood

Question 9

What drug treats implications of G551D mutation in CF?

Answer 9

Ivacaftor (Kalydeco) therapy

Question 10

What are Prenatal Diagnosis (PND) examples?

Answer 10

1. Chorionic villus sampling (CVS)

2. Amniocentesis

Question 11

What is Pre-implantation Genetic Diagnosis (PGD)?

Answer 11

Treatment which involves checking the genes/ chromosomes of embryos for a specific genetic condition. Need to have IVF (embryos tested in lab), even if no fertility problems

Question 12

Presentation of spinal muscular atrophy (SMA)?

Answer 12

• Respiratory difficulties
• Difficult sucking and swallowing
• Floppy
• Unable to sit (normal: 4-7 months)

Question 13

Other name for SMA?

Answer 13

Werdnig-Hoffmann Disease

Question 14

Pathophysiology of SMA?

Answer 14

• Progressive muscle weakness from degeneration of anterior horn cells
• Autosomal recessive
• 95% cases due to deletion of SMN1 (Survival motor neurone 1)
• 1 in 50 population carry mutation

Question 15

Haplotyping

Answer 15

• Inheritance of chromosome markers around site of disease associated mutation
• Closer the markers are together, the more likely they are to be inherited together
• If homozygous at a locus cannot distinguish chromosomes

Question 16

Why can’t you look directly for mutation in SMA?

Answer 16

• Single cell= very low number of DNA copies
• Problems with contamination = False positive result from mum and dad
• Allele drop out= False negative result from failure to amplify mutation

Question 17

What is an encephalocoele?

Answer 17

• Neural tube defect where brain tissue and overlying meninges herniate out through a defect in the cranium
• Caused by failure of neural tube to close completely during fetal development

Question 18

What are polycystic kidneys?

Answer 18

• Inherited kidney disorder - causes fluid-filled cysts to form in the kidneys
• May impair kidney function
=> kidney failure

Question 19

What is Meckel Gruber syndrome?

Answer 19

• Variable phenotype
• Autosomal recessive
• At least 6 genes

The most common features are:
• Enlarged kidneys with numerous fluid-filled cysts
• An occipital encephalocele 
• Extra fingers and toes (polydactyly)
• Fibrosis in liver

Question 20

Trisomy 13, aka…

Answer 20

Patau syndrome

Question 21

Features of trisomy 13?

Answer 21

• Microcephaly
• Mental retardation
• Microphthalmia
• Cleft lip and palate
• Cardiac defects
• Renal defect
• Umbilical hernia
• Polydactyly
• Rocker-bottom feet

Question 22

Post termination genetic counselling

Answer 22

• Was the diagnosis confirmed?
• Why did it occur?
• Can we ever have a normal baby?
• What tests are available in a future pregnancy?
• Did we make the right decision?

Question 23

Name a mutation for Alzhiemer’s?

Answer 23

PSEN-1

Question 24

Pre-symptomatic testing

Answer 24

• No preventative treatment available
• Pre-symptomatic testing protocol
– Full information on test and limitations (Non-directive)
– Opportunity for facilitated decision making
– Issues to consider
(Insurance, Employment, Relationships)