Download Understanding Genetics in FTD and PPA

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
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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
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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
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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
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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
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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
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 look for similar changes in many people
 helpful to have affected and unaffected family
members
 some genes have been found so far
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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
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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!
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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
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research
participation
 currently known genes
 testing strategies
 research participation
 genetic counselors are your friends!
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FTD/PPA Family Caregiver and Professional
Education and Support Conference 2012
questions?
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