Genetics and Dementia – what
do relatives want to know?
Candy Cooley
NHS National Genetic Awareness Lead
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
Aims of this session:
• Review current understanding of links
between dementia and genes
• Consider how the health professional can
identify those at increased risk
• Discuss the implications for the family
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
“ From
past generations we receive a
few strands of DNA, sometimes a
heritage, a memory of one sort or
another”
Dan Pollen M.D.
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
• Dementia affect around 800,000 people in the
UK
• Causative factors include: age, genes,
environmental factors, lifestyle and overall
general health
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
Most dementia is not inherited
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•
•
•
•
•
•
•
Age
Acquired immunodeficiency syndrome
Central nervous system infections
Vascular disease
Brain tumours
Drug toxicity
Syphilis
Metabolic or nutritional deficiencies
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
So how might you identify a family in
which there is an inherited condition?
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
Diag. 57
Diag. 50
= Female
Diag. 58
Diag. 52
= Male
© 2014 NHS National Genetics and Genomics Education Centre
Diag = Age diagnosed
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
Is there a pattern of people with the condition
in this family?
Diag. 57
Diag. 50
Diag. 58
Diag. 52
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
This is suggestive of a type of inheritance called
Autosomal Dominant
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
Autosomal dominant inheritance where one parent has the condition
Parents
Has
condition
Sperm or eggs
Autosomal dominant inheritance where one parent has the condition
Parents
Sperm or eggs
At conception
Autosomal dominant inheritance where one parent has the condition
Parents
Sperm or eggs
At conception
Has the condition
Has the condition
Does not have
the condition
Does not have
the condition
An example of an Autosomal
Dominant condition
Familial Alzheimer’s disease (FAD)
– Amyloid precursor protein (APP)
– Presenilin 1 (PSEN1)
– Presenilin 2 (PSEN2)
If an alteration is present in only one of the two copies
of these genes inherited from a person's parents, the
person will inevitably develop that form of early-onset
Alzheimer's.
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
Other Inherited forms of dementia
What if you see an individual with a condition
known to be inherited but no-one else in the
family has it?
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
Tay Sachs
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
Tay Sachs
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
? ?
?
?
?
?
?
Tay Sachs
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
Autosomal recessive inheritance where both parents are carriers
Parents
Carrier for the
condition
Sperm or eggs
Carrier for the
condition
Autosomal recessive inheritance where both parents are carriers
Parents
Carrier for the
condition
Sperm or eggs
At conception
Carrier for the
condition
Autosomal recessive inheritance where both parents are carriers
Parents
Carrier for the
condition
Carrier for the
condition
Sperm or eggs
At conception
Does not have the
condition, non-carrier
Carrier for the
condition
Carrier for the
condition
Has the
condition
Examples of Autosomal Recessive inheritance –
causing dementia in children
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•
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•
Ceroid lipofucinosis
Gaugher disease III
Lafora disease
Neimann-Pick type C
Sandoff disease
Late onset Tay-Sachs disease
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
Sporadic Alzheimer’s disease
Genetic alterations known to be associated with
sporadic (late onset) dementia
• Apolipoprotein E – variants (APOE – ε2, ε3, ε4)
Recent Research
• MS4A, CD2AP, CD33 & EPHA1
• BIN1 & ABCA7
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
APOE –ε4
One in 100 people between the ages of 65 and
70 have a form of dementia, compared to one
in six people over the age of 80.
• 1 copy – double or triples lifetime risk
• 2 copies – increases risk five-fold
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
Other causes of dementia
• Frontotemporal dementia – 20-30%
hereditary
• Adrenoleukodystrophy – X linked
• Kearns-Sayres syndrome - Mitochondrial
• Inborn errors in metabolism
• Huntington disease
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
ALERT
ASK
ACT
Know the clues
that might indicate
a genetic condition
Collect appropriate
family history
information
Act on the
information you
have
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
General clues
• Multiple closely related people with the same
condition.
• Disorders which occur at a younger age than
usual (eg colon cancer, breast cancer,
dementia).
• Three or more pregnancy losses
• Medical problems in children of parents related
by blood.
• Congenital anomalies, dysmorphic features
and developmental delay.
© 2012 NHS National Genetics Education and Development Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
ASK
Collect appropriate
family history
information
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
What information should you collect?
•Information depends on the context and reason for
collecting it:
•Establish biological relationships
•Clarify the medical conditions that people have
•3 generations
•For each person:
•Full name
•Date of birth (or age)
•Date of death (or age died)
•Medical information (age at diagnosis)
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
Drawing a family tree
Marriage /
Partnership
(horizontal line)
Male
Female
/
Partnership that has
ended
Person whose sex
is unknown
P
Pregnancy
Offspring (vertical
line)
Miscarriage
X weeks
Affected Male &
Female
Parents and Siblings
Carrier Male & Female
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
ACT
Act on the
information
you have
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
www.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Development Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
Implications for the family
• “My feeling is I’d only want to
know if there’s something I can do
about it”
• “For me, it’s pretty scary when I
forget where I parked my car. I
think, ‘Here it is, here I go.”
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
• Reassure
– Knowledge of the condition
– Local/national referral guidelines
• Refer
– To the GP or clinical genetics service
• Seek further advice
– Trusted sources of information
– Clinical Genetics Department On-Call Service
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
• Clinical Genetics Services
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
www.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk