Download Clinical Genetics - Asia Pacific Coroners Society

Cardiac Genetics Clinic (Adult)
Queensland
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Awareness of improved testing
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Need for formalised family follow up
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Developed combined clinic from Feb 07
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Clinical genetics and cardiology
Hypertrophic cardiomyopathy

Autosomal dominant

1 in 500

Commonest cause of sudden cardiac
death in individuals <35years

Mutations identified in 11 genes, mostly
encoding sarcomere proteins
Testing issues
Many genes, many mutations
 Availability
 Cost
 More than one mutation
 Consent
 ELSI
 Children
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Testing

10 genes screened
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Family history: 60% chance finding
mutation
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No family history: 30% chance
Availability
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Not currently in Australasia

Long QT being developed
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Main centre = Denmark
Cost of screening

On basis of guidelines, if screen from 10-60 years in
4 at risk family members

Minimal costs for clinical assessment, echo and ECG
= about $30000

To test 4 at risk relatives if mutation known
= $1000

PhD ongoing looking at Health Economic Analysis of
Cardiac Genetic Diseases in Australia (including
Quality of Life data)
More than one mutation

Number of studies shown people with 2
mutations in same gene or different
genes

Interpretation difficult within families

Could be related to clinical course ie
may be more severe
Consent

Need to explain limitations of testing

Possibility of 2 mutations and family
studies necessary

Be aware of consequences ie if
asymptomatic will be then be considered
“affected”

Screening/ interventions possible
Children
Not able to give informed consent
 Issues of confidentiality
 Pros v cons
 Discrimination
 Loss of opportunity
 When to test
 Why?

Testing children

Is there any medical benefit?

Undertake regular cardiological examination in all
children who are first degree relatives
11-20y: annually


until hypertrophy appears or until the child reaches
the age and maturity to make his/her decision

genetic testing may be performed in selected cases
eg child in competitive sports
Development of protocols

Determine reasonable age clinically

Use team approach involving child
psychiatry

Have some justifiable flexibility

Individual approach
Future developments

Ongoing development Australasian
guidelines

Consider funding and develop testing for
more conditions with appropriate
interpretation

Collaboration and research; CIDG,
TRAGADY
Sudden unexplained death
Up to 400000 deaths US/year
 Mostly cardiac disorders
 >40 y coronary artery disease most
prevalent cause
 Younger; PM indicate 60-75% have
potentially inherited diseases
 In clinical practice, many remain
unexplained

Surviving relatives

Family members of 43 SUD

183 surviving relatives

Familial disease identified in 17 families
(40%) on clinical evaluation

Clinical evaluation useful in family
members
Surviving relatives

12 involved primary electrical disease

Mutations in 10 families

Finding the diagnosis more likely when
more relatives were examined, more
family members affected
Role of Molecular Genetics
Very useful
 In those where no cause identified on
PM, may make the diagnosis
 May confirm the diagnosis where
equivocal
 May confirm the diagnosis
 Important to accurately identify affected
family members

Potential problems in clinical
screening alone





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How many relatives need to be/are
screened?
How long for?
If no-one clearly affected on screening,
what does it mean for rest of family?
Who to DNA test if no-one apparently
clinically affected?
Would numerous relatives be tested?
If test 5 and no mutation, is an inherited
condition ruled out?
Usual Practice in Molecular Testing
Test an affected individual
 Higher likelihood of abnormality
 May be a new mutation
 Even if not, only 50% relatives may
carry it; if clinically unaffected who to
test?
 In these families, affected individual
presents dead

?Arrhythmia
3y
5y
Extended family normal clinically
No confirmed diagnosis in parent
Unknown risk for children; too young to test in own right
SUD 34y male ?VF
Couple of “faints”
Numerous cardiac investigations and follow up
No sample available for testing from brother
?? Access and consent
Continued uncertainty
HCM family
?
Due for ICD;
Would lose job
Estranged
ICD
No mutation, no ICD
Mutation found
HCM
42y
12y
16y
Not clinically affected; is it because no mutation or unaffected?
Need significant screening
Need mutation analysis in proband
Family assessment
May need to screen many times over a
number of years
 Clinical screening not always able to
detect mutation carriers
 Affected proband best to test; we know
they are affected
 If proband dead, unable to access
samples and obtain consent

Coroners Act (Queensland)
Section 3. 3
d) help to prevent deaths from similar
causes happening in the future by
allowing coroners at inquests to
comment on matters connected with
deaths, including matters related to (i) public health or safety; or (ii) the
administration of justice.

Ideal
Molecular testing samples taken by
forensic pathologist to enable molecular
determination/confirmation cause of
death in conjunction with;
 Possibility/confirmation of inherited
condition raised with family and detailed
family history to inform any potential
testing
 Family referred to cardiac genetics clinic
 Screening clinical and/or genetic testing
carried out
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