the knowns and unknowns: genetic testing and congenital heart disease by kirsten bartels
TRANSCRIPT
The Knowns and Unknowns: Genetic testing and Congenital Heart Disease
Kirsten Bartels, MSc, CCGCGenetic CounsellorHeritable Aortopathies Clinic (Part of PACH clinic)St. Paul’s Hospital
Unique Hearts, Unique Lives07 May 2016
Let’s talk genetics.
•
Genetics 101–
What is a gene?
–
How do genes cause disease?
–
How are genetic diseases inherited?
•
Genetics of Heart Disease–
Genetic counselling
–
Genetic testing and diagnosis
Genetics 101What is a gene?
gene
Genetics 101How do genes cause disease?
geneXX
X
Genetics 101How are genetic diseases inherited?
Autosomal Dominant Autosomal Recessive
Genetics 101How are genetic diseases inherited?
X‐linked recessive, fatherX‐linked recessive, mother
Genetics 101
How are genetic diseases inherited?
–
Multifactorial (eg. isolated heart defects)•
(Usually) no genetic testing possible
•
Recurrence risk based on study estimates
–
Sporadic (eg. Down syndrome)
MYTH or FACT?I look more like my dad, so I have more of his DNA and I am more likely to develop his health problems down the road.
ANSWER:MYTH! We inherit 50% of our DNA from each parent, regardless of which parent we physically resemble. It is important to be aware of the family health history on both sides of the family.
MYTH or FACT?About 60% of humans DNA sequence is the same as bananas.
ANSWER:FACT! We share considerable similarities to many different animals and plants, including bananas!
Genetics of Congenital Heart Disease
Heart Defects (isolated)Tetralogy of Fallot, Ventricular Septal Defect, Coarctation of the Aorta, etc.
Heart Defects with other featuresDown syndrome, Williams syndrome, 22q11 microdeletion, VATER,
CHARGE, etc.
Aortic disease and connective tissue disordersMarfan, Familial aortic aneurysm, Ehlers‐Danlos, etc.
Heart Muscle Disease with other featuresNoonan, Glycogen storage disease, Fabry disease, Amyloidosis, etc.
Heart Muscle Disease (isolated)Hypertrophic CM, Dilated CM, Restrictive CM, Noncompaction CM,
ARVD/ARVC
Heart Rhythm ConditionsLong QT, Short QT, Brugada, CPVT
Genetic Counselling
Why did this occur?
Will it happen again in our family?
Who else is at risk?
• Specialized education (medical genetics and counseling)
• Members of a healthcare team
• Information and support to individuals and families at risk for, or diagnosed with, a variety of inherited conditions
What is a Genetic Counsellor?
Genetic services in BC:–
Vancouver:•
Provincial Medical Genetics Program (BC Women’s)
•
BC Inherited Arrhythmia Program (St. Paul’s Hosp/BCCH)•
Heritable Aortopathy Clinic (part of PACH clinic @ St. Paul’s Hosp)•
Hypertrophic Cardiomyopathy Clinic (St. Paul’s Hosp)
–
Victoria•
Medical Genetics Clinic (Victoria General Hosp)
MYTH or FACT?Genetic counsellors only meet with individuals who are pregnant, or are planning a family.
ANSWER:MYTH! Genetic counsellors meet with individuals who may be at risk for genetic conditions at all stages of life.
MYTH or FACT? I have a family history of aortic aneurysm. I can’t change my genetics so genetic counselling is not important.
ANSWER:MYTH! Genetic counselling can help you understand your family history. For some people genetic testing can clarify their chance of developing aortic disease… and how to find it early!
MYTH or FACT?I can see a genetic counsellor without having to undergo extensive genetic testing.
ANSWER:FACT! Genetic counsellors meet with patients who desire a risk assessment regarding a particular heritable condition. Testing is not always offered. However, even if genetic testing is offered, it is up to the patient to decide whether they would like to proceed.
Steve
Marfan Syndrome?Connective Tissue Disorder?
CardiologistNurseGenetic Counsellor
Marfan syndrome
Genetic cause:
FBN1
gene
Inheritance:
Autosomal
dominant
•
Congenital heart disease–
Aorta enlargement/aneurysm–
Aortic tear or rupture–
Mitral valve prolapse
•
Bone overgrowth and joint laxity–
Scoliosis•
Ectopia lentis (lens dislocation)
Gene sequencing analysis
gene X
Steve
“Probable” Marfan
syndrome
No family historynew daughter
Criteria
Why do genetic testing?
– Confirmation of diagnosis
– Guide treatment and management
– Screening tool for relatives• Inheritance/recurrence risk• Prenatal diagnosis • Preimplantation genetic diagnosis
Genetic testing limitations• Not available for all conditions
– Although the role of many genes is known and we can test for many diseases, there is still a lot to learn
• Genetic testing does not detect 100% of disease causing mutations– In many cases, negative results would be considered
inconclusive and would not completely rule out a diagnosis
• Genetic information is not always straightforward in its meaning– Some results are subject to ambiguity and interpretation and are
not clear cut
DiscriminationDifferential treatment of an asymptomatic person on the basis of
their genetic characteristics predicted from a genetic test result or
their family history
Historically, most accounts were based on anecdotal or unverified
data
www.ccgf‐cceg.ca
(Canadian Coalition for Genetic Fairness)www.genome.gov/10002077 (GINA, USA)
MYTH or FACT?I don’t need Genetic Counselling regarding the disease in my family as my mom went when I was young.
ANSWER:MYTH! With changes in technology and knowledge, there is often new information for families with genetic conditions.
