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Printable Handouts
Navigable Slide Index
- Introduction
- Table of contents
- UK FH NICE guidelines 2008 - update 2017
- Why not just measure LDL-C?
- DNA testing for identification of relatives
- How does cascade testing work?
- Family A
- Genetic causes of FH in the UK
- What is the frequency of HetFH in the UK?
- What is the overall mutation detection rate?
- No-mutation patients?
- No-mutation FH patients: polygenic cause?
- Relationship between gene score and LDL-C levels
- Weighted gene score in FH/M- vs. WHII
- Why is the polygenic explanation important?
- Higher CAD risk in monogenic vs. polygenic high LDL-C (1)
- Higher CAD risk in monogenic vs. polygenic high LDL-C (2)
- Results: association of score with CVD risk (HR)
- Hazard ratio for CVD risk in mFH vs. PGH vs. NGH
- Conclusions
Topics Covered
- Familial hypercholesterolaemia
- UK FH-NICE guidelines
- Cascade testing of family members
- Genetic testing for FH
- Genetic causes of FH in the UK
- Monogenic causes of FH phenotype
- Polygenic causes of FH phenotype
- Clinical consequences of monogenic vs. polygenic causes
Links
Series:
Categories:
Therapeutic Areas:
External Links
Talk Citation
Humphries, S. (2023, August 31). Familial hypercholesterolaemia: cascade testing and monogenic vs. polygenic causes [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 8, 2024, from https://doi.org/10.69645/CLXU4211.Export Citation (RIS)
Publication History
Financial Disclosures
- Professor Humphries is the Medical Director of StoreGene a UCL spin out company that offers DNA testing for Cardiovascular Disease risk including testing for FH. Professor Humphries is a consultant for Verve Therapeutics, a US based company that is developing gene-editing agents to treat individuals with hypercholesterolaemia, including those with FH.
Familial hypercholesterolaemia: cascade testing and monogenic vs. polygenic causes
Published on August 31, 2023
22 min
A selection of talks on Clinical Practice
Transcript
Please wait while the transcript is being prepared...
0:00
My name is Steve Humphries.
In the second part we're
going to talk about
cascade testing and comparing
monogenic and polygenic
causes of the FH phenotype.
0:16
In 2008 the UK NICE guidelines
were developed and
they were updated in
2017 and they have a number of
different
recommendations and I'm
just going to give you
some of the headlines.
Their aim for
treatment is to lower
LDL cholesterol by at
least 50% from baseline.
I've already shown
you that that's
feasible but it certainly
doesn't deal with
all the problems of people
with extremely high
LDL cholesterol.
The European Atherosclerosis
Society, the
EAS has set a target of 2.5mmol/l
if an individual with FH
doesn't have heart
disease and 1.8mmol/l
if they do have heart disease,
and with the new agents
those targets are now
certainly achievable.
The guidelines say
that for diagnosis
all individuals should
be offered a DNA test to
confirm the diagnosis
and to assist in
cascade testing of
relatives and I'll
explain how cascade
testing works later.
In children under the
age of 10 at risk of FH,
in other words they
have one affected
parents, they should be offered
a DNA test at
the earliest opportunity
and definitely by 10 years,
because 10 years is the
age when you should
consider initiation
of statin treatment.
Finally, the guidelines say
that identifying people
with FH using
cascade testing and
DNA information
is recommended to
identify the affected
relatives and here,
a document that
we produced about
implementing a systems approach
to detection and management,
and it's available for you
to download using the link.
Once again very clear knowing
the family mutations
a key piece of
information for testing
relatives and for
starting statin therapy
particularly in childhood.
But now why not simply measure
LDL cholesterol isn't that
going to be diagnostic enough?
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