Genetics and Dementia – what do relatives want to know? Candy Cooley NHS National Genetic Awareness Lead Genetics and genomics for healthcare

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



“ From past generations we receive a few strands of

DNA, sometimes a heritage, a memory of one

sort or another”Dan Pollen M.D.



• Dementia affect around 800,000 people in the UK

• Causative factors include: age, genes, environmental factors, lifestyle and overall general health



Most dementia is not inherited• Age• Acquired immunodeficiency syndrome• Central nervous system infections• Vascular disease• Brain tumours• Drug toxicity• Syphilis• Metabolic or nutritional deficiencies



So how might you identify a family in which there is an inherited condition?



Diag = Age diagnosed

Diag. 57

Diag. 50 Diag. 58

Diag. 52= Female

= Male



Is there a pattern of people with the condition in this family?

Diag. 57

Diag. 50 Diag. 58

Diag. 52



This is suggestive of a type of inheritance called Autosomal Dominant



Parents

Autosomal dominant inheritance where one parent has the condition

Sperm or eggs

Has condition

Parents

Sperm or eggs

At conception


Parents

Sperm or eggs

At conception


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.



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?



Tay Sachs



Tay Sachs



Tay Sachs

? ?

? ?

? ?

?



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


Carrier for the

condition

Carrier for the

condition

Parents

Sperm or eggs

At conception


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



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



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



Other causes of dementia

• Frontotemporal dementia – 20-30% hereditary

• Adrenoleukodystrophy – X linked• Kearns-Sayres syndrome - Mitochondrial• Inborn errors in metabolism• Huntington disease





General clues


© 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.



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)





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







www.geneticseducation.nhs.ukGenetics and genomics for healthcare

www.geneticseducation.nhs.uk© 2014 NHS National Genetics and Genomics Development 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



• Clinical Genetics Services



www.geneticseducation.nhs.uk



Documents

Genetics and Dementia – what do relatives want to know? Candy Cooley NHS National Genetic Awareness Lead Genetics and genomics for healthcare