Genetics and Dementia – what do relatives want to know? Candy Cooley NHS National Genetic...
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Transcript of Genetics and Dementia – what do relatives want to know? Candy Cooley NHS National Genetic...
Genetics and Dementia – what do relatives want to know?
Candy CooleyNHS National Genetic Awareness
Lead
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
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
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
“ From past generations we receive a few strands of
DNA, sometimes a heritage, a memory of one
sort or another”Dan Pollen M.D.
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
• Dementia affect around 800,000 people in the UK
• Causative factors include: age, genes, environmental factors, lifestyle and overall general health
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
Most dementia is not inherited• Age• Acquired immunodeficiency syndrome• Central nervous system infections• Vascular disease• Brain tumours• Drug toxicity• Syphilis• Metabolic or nutritional deficiencies
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
So how might you identify a family in which there is an inherited condition?
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
Diag = Age diagnosed
Diag. 57
Diag. 50 Diag. 58
Diag. 52= Female
= Male
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
Is there a pattern of people with the condition in this family?
Diag. 57
Diag. 50 Diag. 58
Diag. 52
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
This is suggestive of a type of inheritance called Autosomal Dominant
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
Parents
Autosomal dominant inheritance where one parent has the condition
Sperm or eggs
Has condition
Parents
Sperm or eggs
At conception
Autosomal dominant inheritance where one parent has the condition
Parents
Sperm or eggs
At conception
Autosomal dominant inheritance where one parent has the condition
Has the conditionHas the conditionDoes 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.
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
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?
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
Tay Sachs
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
Tay Sachs
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
Tay Sachs
? ?
? ?
? ?
?
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
Parents
Sperm or eggs
Autosomal recessive inheritance where both parents are carriers
Carrier for the
condition
Carrier for the
condition
Parents
Sperm or eggs
At conception
Autosomal recessive inheritance where both parents are carriers
Carrier for the
condition
Carrier for the
condition
Parents
Sperm or eggs
At conception
Autosomal recessive inheritance where both parents are carriers
Carrier for the
condition
Carrier for the
condition
Does not have the condition, non-
carrier
Carrier for the
condition
Has the condition
Carrier for the
condition
Examples of Autosomal Recessive inheritance – causing dementia in children
• Ceroid lipofucinosis• Gaugher disease III• Lafora disease• Neimann-Pick type C• Sandoff disease• Late onset Tay-Sachs disease
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
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
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
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
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
Other causes of dementia
• Frontotemporal dementia – 20-30% hereditary
• Adrenoleukodystrophy – X linked• Kearns-Sayres syndrome - Mitochondrial• Inborn errors in metabolism• Huntington disease
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
General clues
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2012 NHS National Genetics Education and Development Centre
• 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.
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
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)
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
Drawing a family tree
Male
Female
Person whose sex is unknown
PregnancyP
Marriage / Partnership(horizontal line)
Parents and Siblings
Offspring (vertical line)
Affected Male & Female
Carrier Male & Female
Partnership that has ended
/
X weeks
Miscarriage
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
www.geneticseducation.nhs.ukGenetics and genomics for healthcare
www.geneticseducation.nhs.uk© 2014 NHS National Genetics and Genomics Development Centre
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
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.”
• 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
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
• Clinical Genetics Services
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre
www.geneticseducation.nhs.uk
Genetics and genomics for healthcarewww.geneticseducation.nhs.uk
© 2014 NHS National Genetics and Genomics Education Centre