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FTD/PPA Family Caregiver and Professional Education and Support Conference 2012 agenda genetic counseling genetics 101 genetics of FTD and PPA genetic testing research Lisa Kinsley, MS, CGC, genetic counselor HyungSub Shim, MD, neurology fellow, CNADC how does my family fit in? what to expect what is a genetic counselor? translator patient advocate resource negotiator genetics 101 educator decision facilitator cell nucleus chromosomes gene Copyright 2012 Please Do Not Replicate or Distribute Without Permission 1 FTD/PPA Family Caregiver and Professional Education and Support Conference 2012 DNA to protein gene cell nucleus chromosomes protein bone cell pancreas cell brain cell DNA to protein with a mutation gene cell nucleus chromosomes 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 protein egg X Y autosomal dominant inheritance sperm males and females affected equally fertilized egg cannot skip a generation mutation 50% chance to pass mutation on use pedigree to look for patterns of inheritance reproductive bone pancreas brain body cells of offspring Copyright 2012 Please Do Not Replicate or Distribute Without Permission 2 FTD/PPA Family Caregiver and Professional Education and Support Conference 2012 autosomal dominant inheritance m d m d m d m d autosomal dominant inheritance d m d m pedigree helps with… polymorphisms pattern of inheritance change in a gene that does not affect function identification of individuals at risk color vs. colour genetic testing strategies screen for other medical risks genetics of FTD about 10% of FTD cases are inherited sporadic FTD ~50-70% not inherited no other affected family members no increased risk for family members 50-70% of FTD cases are sporadic (not inherited) 20-40% of FTD cases are familial Copyright 2012 Please Do Not Replicate or Distribute Without Permission 3 FTD/PPA Family Caregiver and Professional Education and Support Conference 2012 sporadic FTD Inherited FTD about 10% of all FTD affected parent means 50% risk to first degree relatives lower age of onset and more rapid course than sporadic FTD inherited FTD familial FTD 20 – 40% has a heritable component intermediate risk to family members lower age of onset quicker disease course multifactorial disease familial FTD Inheritance the thought of inheriting and/or passing down a mutation associated with FTD is scary we know some, but not all about FTD genetics Copyright 2012 Please Do Not Replicate or Distribute Without Permission 4 FTD/PPA Family Caregiver and Professional Education and Support Conference 2012 which type of FTD is my family? medical history work with genetic counselor accurate medical history means more accurate risk estimation limitations – early death of relatives, adoption, no information any and all medical information is helpful! medical records, autopsy reports, tissue blocks, etc any and all conditions, especially neurological ALS, FTD, PD gray areas of genetics FTD much of genetics is not a simple yes or no we inherit risk levels for any given condition this risk is modified throughout our lives some genes are known PD FTD not much is known about environmental factors ALS gray areas of genetics genetic research many families fall within the middle area blood and/or tissue samples no testing available no specific risk number research participation is an option keep in touch with neurologist and genetic counselor Copyright 2012 Please Do Not Replicate or Distribute Without Permission look for similar changes in many people helpful to have affected and unaffected family members some genes have been found so far 5 FTD/PPA Family Caregiver and Professional Education and Support Conference 2012 MAPT microtubule associated protein tau chromosome 17 makes a protein called ‘tau’ present in the brains of people with neurodegenerative disorders MAPT families FTDP-17 dementia and/or parkinsonism brain atrophy healthy tau removed by normal processes abnormal tau has altered function and cannot be removed like normal tau this leads to symptoms more than 2 family members affected in an AD pattern MAPT mutation PGRN around 40 mutations reported progranulin unique vs. common mutations chromosome 17 genotype/phenotype correlations? progranulin sends a message to increase cell growth disease course, symptoms, age helps would repair, related to cancer useful for genetic counseling of families lots of other functions function in FTD is unclear still variation within families – why? polymorphisms mutation leads to not enough functional progranulin CBD, PSP or modified FTD risk PGRN families PGRN mutation increased chance for PPA brain protein is also common in ALS decreased chance for MND polymorphims in PGRN lead to susceptibility more variable than MAPT more studies are needed! aphasia behavior disorders reports of individuals in their 70s with no symptoms Copyright 2012 Please Do Not Replicate or Distribute Without Permission 6 FTD/PPA Family Caregiver and Professional Education and Support Conference 2012 future directions for research genetic counseling session genotype/phenotype correlations family history and analysis progranulin and TDP-43 proteins natural history, genetics and inheritance education related substances may mean drugs for treatment data update discuss recurrence risks review genetic testing psychosocial support genetic testing presymptomatic testing complex! only possible with a known gene who to test? “true negative” test result research vs. clinical testing other considerations what gene? testing strategies testing: yes or no? family communication reasons to test reasons not to test need to know no treatment plan finances no cure have a meeting with family and genetic counselor insurance hypervigilance for symptoms lots of possible reactions, all are normal and okay open and honest, ideally include a discussion of genetic testing this is a very individual decision! Copyright 2012 Please Do Not Replicate or Distribute Without Permission 7 FTD/PPA Family Caregiver and Professional Education and Support Conference 2012 genetic testing genetic testing meet with genetic counselor one person affected in the family no clinical testing recommended (unlikely to be helpful) research participating for affected individual and family meet with genetic counselor several people affected, no clear pattern multiple generations affected with an AD pattern consider MAPT or PGRN clinical testing consider MAPT or PGRN clinical testing mutation found no mutation found presymptomatic testing possible research participation mutation found no mutation found presymptomatic testing possible research participation genetic testing one person affected in the family no clinical testing recommended (unlikely to be helpful) research participating for affected individual and family no clinical testing recommended (unlikely to be helpful) research participating for affected individual and family multiple generations affected with an AD pattern consider MAPT or PGRN clinical testing consider MAPT or PGRN clinical testing no mutation found presymptomatic testing possible research participation mutation found no mutation found presymptomatic testing possible research participation research participating for affected individual and family no mutation found presymptomatic testing possible research participation mutation found presymptomatic testing possible no mutation found research participation one person affected in the family no clinical testing recommended (unlikely to be helpful) research participating for affected individual and family several people affected, no clear pattern multiple generations affected with an AD pattern consider MAPT or PGRN clinical testing consider MAPT or PGRN clinical testing mutation found presymptomatic testing possible no mutation found research participation mutation found presymptomatic testing possible no mutation found research participation summary meet with genetic counselor no clinical testing recommended (unlikely to be helpful) consider MAPT or PGRN clinical testing meet with genetic counselor genetic testing one person affected in the family consider MAPT or PGRN clinical testing genetic testing several people affected, no clear pattern mutation found multiple generations affected with an AD pattern mutation found meet with genetic counselor one person affected in the family several people affected, no clear pattern several people affected, no clear pattern multiple generations affected with an AD pattern consider MAPT or PGRN clinical testing consider MAPT or PGRN clinical testing majority of FTD/PPA is not inherited accurate medical histories risk assessments mutation found presymptomatic testing possible no mutation found research participation mutation found no mutation found presymptomatic testing possible Copyright 2012 Please Do Not Replicate or Distribute Without Permission research participation currently known genes testing strategies research participation genetic counselors are your friends! 8 FTD/PPA Family Caregiver and Professional Education and Support Conference 2012 questions? Copyright 2012 Please Do Not Replicate or Distribute Without Permission 9