genetic counseling for als: things to considergenetic counseling 1. education (information giving)...
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Genetic Counseling for ALS: Things to Consider
Ellie Harrington, MS, CGC
Genetic Counselor
The Eleanor and Lou Gehrig ALS Center
January 28th, 2019
Andrea Smith, MS, CGC
Outreach Professional
ALS Association of North Carolina
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Outline
• Genetics and Genetic Counseling 101
• ALS Genetics – What We Know
• Genetic Counseling for ALS
• Clinical trials
• Resources
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Genetic Counseling
1. Education (information giving) about inheritance, natural history, testing options, medical management, prevention, social support and research;
2. Assessment of the chance for recurrence or occurrence of a condition, after information gathering and establishing/verifying the diagnosis, and
3. Counseling and psychological support to help clients adapt to their situation and choices, and to the psychological, familial and social issues that stem from the risk or condition in the family.
Genetic Counseling is the practice of helping individuals and families understand the medical, psychological, social and reproductive
implications of genetic and congenital conditions.
Journal of Genetic Counseling, Vol. 15, No. 2, April 2006
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Education – Basic Genetics
HUMAN BODY CELL CHROMOSOMES
DNA
GENESPROTEINFUNCTION G A
C T
Harrington, Elizabeth MS, CGC, 2019Google Images
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Assessment – familial or sporadic ALS(fALS/sALS)
• Pedigree analysis• Is there a family history?
• Familial vs. Sporadic (fALS/sALS):
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Sample – family history example
d. ALS
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Assessment – familial or sporadic ALS(fALS/sALS)
• Pedigree analysis• Is there a family history?
~90%
~10%
Familial ALS (fALS)
Sporadic ALS (sALS)
sALS
~11% Known
genetic cause
fALS
~66% Known
genetic cause
• Familial vs. Sporadic (fALS/sALS):
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Features of fALS
Renton et al. Nature Neuroscience 2013
• Generally, the symptoms of FALS are the same as the symptoms of SALS though exceptions exist
• The average age that individuals with FALS begins to have symptoms of ALS is 46 compared to the average age of symptom onset in individuals with SALS which is 56
• Variability in the age of symptom onset and disease progression between families and between members of the same family is common
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ALS gene discovery
Renton et al. Nature Neuroscience 2013
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Genetic risk
• Inheritance• Autosomal dominant > autosomal
recessive >> X-linked
• Penetrance• The proportion of individuals carrying
a particular variant of a gene that also express the associated symptoms or phenotype
Autosomal dominant
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C9orf72 • European founder effected detected in Scandinavia (Finland)
• Accounts for ~40% fALS and ~7-10% sALS
Frontotemporal dementia• Also major genetic cause for
frontotemporal dementia (FTD)• Accounts for ~25.9% of familial FTD
• Incomplete penetrance• 50% by age 58, nearly 100% by age 80
• Autosomal dominant inheritance
sALS
~11% Known
genetic cause
fALS
~66% Known
genetic cause
Van Blitterswijk et al., Curr Opin Neurol. 2012
7-10% of ~11%
~40% of ~66%
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Typical C9orf72 (GGGGCC) repeat size
Expanded C9orf72 (GGGGCC GGGGCC)
repeat size
Expanded C9orf72 (GGGGCC GGGGCC)
repeat size
Typical C9orf72 (GGGGCC) repeat size
Autosomal dominant C9orf72
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SOD1
• Accounts for ~20% of fALS
• Causes typical ALS
• ~50% of individuals with SOD1 mutation are symptomatic by age 46 years; 90% are symptomatic by age 70 years
• Autosomal dominant inheritance
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Genetic counseling
• Counseling and psychological support to help clients adapt to their situation and choices, and to the psychological, familial and social issues that stem from the risk or condition in the family.
• Help individuals decide if genetic testing is right for them
• Review benefits and risks
• Discuss implications for individual and their family members
Journal of Genetic Counseling, Vol. 15, No. 2, April 2006
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Genetic testing
• Reasons some chose to test• Find out “what” the cause of disease
is or “why” it occurred
• Potential to enroll in clinical trials
• Knowledge of risk for family members
• Family planning
• Reasons some chose not to test• Psychological considerations –
increased anxiety
• Result wouldn’t change care plan
• Insurability risks GINA• (Genetic Information
Nondiscrimination Act) 2008 www.ginahelp.org
• Protects individuals against health insurance companies and employers from discrimination against genetic information
• Does NOT include: life insurance, long-term care, or disability insurance
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Drug Development and Research for fALS
• BIIB078 (IONIS-C9Rx) for c9orf72
• BIIB067 (IONIS-SOD1Rx ) for SOD1
• Pre-fALS: The Pre-symptomatic Familial ALS Study
How to find out more:
• http://www.alsa.org/research/clinical-trials/?state=
• www.clinicaltrials.gov
• ALS trial liaison: Carly Doyle, (855) 437-4823, [email protected]
• http://www.alsa.org/research/research-news/research-webinars.html
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Presymptomatic genetic testing
• Testing at risk family members who do not exhibit symptoms
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d. ALS
+ C9orf72 gene mutation
50% chance inherited C9orf72
mutation
Pre-symptomatic genetic testing - example
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Presymptomatic genetic testing
• Testing at risk family members who do not exhibit symptoms• Confirmed familial mutation
• Genetic Counseling for family members• Explore individuals experience with ALS in family
• Discuss the reasons and desire to learn this information• Is this a good time in their life to learn their genetic status?
• Explore how this result may impact their life –• Impact on relationships and family
• Family planning
• Insurances
“Genetic Testing Protocol for Huntington’s Disease”. © 2016 Huntington’s Disease Society of America
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Presymptomatic genetic testing – family planning
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Genetic counseling session(s)
1. Why test? • Find out “what” the cause of disease is or “why” it occurred • Potential to enroll in clinical trials• Knowledge of risk for family members• Family planning
2. Informed consent • Implications for individual• Implications for family members
3. Return of results• Where to go from here?
• Processing of the personal genetic test result• Conversations with family members • Clinical trial opportunities and hope for future
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Summary
• Sporadic ALS is most common (~90%)• Causative gene mutation found in ~11% of sALS and ~66% of fALS
• 20+ ALS associated genes – variable inheritance, penetrance, expressivity
• C9orf72 is the most common gene associated with ALS and FTD
• Clinical genetic testing may be useful for:• Participation in clinical trials
• Knowledge for at-risk family members
• Genetic testing for at-risk family members may be possible when a gene mutation is first confirmed in a family member with ALS
• Talk to your physician about questions regarding genetic testing• Find a genetic counselor through the National Society of Genetic Counselors
• NSGC website: https://www.nsgc.org/
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Andrea Smith, MS, CGC
Outreach Professional
ALS Association of North Carolina
Questions?
Ellie Harrington, MS, CGC
Genetic Counselor
The Eleanor and Lou Gehrig ALS Center