Challenges of genetic testing in Hypertrophic Cardiomyopathy

Challenges of genetictesting in HypertrophicCardiomyopathyAssociate Professor Julie McGaughranGenetic Health Queensland

Cardiac Genetics Clinic• 10 year research interest in cardiomyopathies• Awareness of improved testing• Need for formalised family follow up• Developed combined clinic from Feb 07

Hypertrophic cardiomyopathy• Autosomal dominant• 1 in 500• Commonest cause of sudden cardiac deathin individuals

AttendancePatient Attendees200150100500Year 2007 Year 20082007: 70 patients2008: 147 patients

Genetic testing50403045 diagnostic18 predictive20100DiagnosticPredictive

Testing issues• Many genes, many mutations• Availability• Cost• More than one mutation• Phenotype/genotype correlation

Availability• Specialised tests• Useful for centres to develop excellence• Not available in Australia• Currently send to Denmark lab (StatensInstitute)

Testing• 11 genes screened• Family history: 60% chance finding mutation• No family history: 30% chance• Queensland to date; 62% mutation detection

Cost• No Federal funding for vast majority ofgenetic tests• Variable access to state funding• Currently $2000/screen• Funded by state in Queensland (so far)

Cost of screening• On basis of guidelines, if screen from 10-60 years in4 at risk family members• Minimal costs for clinical assessment, echo and ECG= about $30000• To test 4 at risk relatives if mutation known= $1000

More than one mutation• Number of studies shown people with 2mutations in same gene or different genes• Interpretation difficult within families• Could be related to clinical course ie may bemore severe

Genotype/phenotype correlation• Can the gene mutation predict clinicalcourse?• Can it aid management?• Generally, no

MYH7: V606M mutation“Benign mutation”Apparently unaffected 70s?ICDICD 12y

Family TestingICDTested negative for familial mutation twiceHas mild hypertrophy

M familyOut of hospital arrestSignificant HCMAll family assessedand clinically normal

After mutation testing...Management of mutation positive, phenotype negative?

Consent• Need to explain limitations of testing• Possibility of 2 mutations and family studiesnecessary• Be aware of consequences ie if asymptomaticwill be then be considered “affected”• Issues with children

Future developments• Ongoing development Australasianguidelines• Consider funding and develop testing formore conditions with appropriateinterpretation• Expand clinic eg FH• Collaboration and research; forensicpathology, coroner

To finishCousin with HCM in Holland82 years, normal examination

Thank you?

Genes Screened• MYH7• MYBPC3• MYL2• MYL3• TNNT2• TPM1• ACTC• TNNI3• CSRP3• TCAP• Promoter and coding regions PLN

Children• Not able to give informed consent• Issues of confidentiality• Pros v cons• Discrimination• Loss of opportunity• When to test• Why?