Cascade testing for genetic heart conditions

Familial hypercholesterolaemia (FH) is much more common than people realise. We now know that it probably affects around one in 250 people in the UK, which is twice the estimate of a few years ago. To give you a sense of scale, that means it is similar to the numbers of cases of childhood type 1 diabetes.

This is an inherited condition due to a single genetic mutation, which means that someone has high cholesterol levels (specifically low-density lipoprotein or ‘bad’ cholesterol) from birth onwards.  This leads to early cardiovascular disease, such as heart attack or stroke, but it can be undiagnosed for years. Tragically, people can appear outwardly healthy, and be fit and well until an acute event, such as a sudden cardiac death. Children with FH will show no obvious signs at all. There are also cases where people with FH have been identified as having high cholesterol and put on statins, without finding the underlying genetic cause.

In the past, we had to rely on a set of diagnostic criteria using the Simon Broom register, which is based on a high cholesterol test, family history, (family members who have a premature heart attack, or raised cholesterol), and visible signs such as corneal arcus, where a white arc appears in the coloured part of the eye, and fatty deposits on the tendons known as tendon xanthomas.

Today, we are relying on genetic testing to find the faulty gene that leads to the condition.

Cascade testing is when we test all the first degree relatives of someone who is diagnosed with FH, meaning that we can identify not just a single patient, but all the others who may have the condition in his or her immediate family.  Because the FH mutation is dominantly inherited, 50 per cent of the offspring will inherit the gene from a parent who carries the fault.  On average each of us will have 5 or 6 first degree relatives (siblings, parents and children), so you can expect to identify 2 or 3 new cases from each cascade test.

Cascade testing enables cases of FH to be picked up at a younger age and offered genetic diagnosis. The earlier patients with FH are identified, the better the health outcomes. Cascade testing can also reveal when someone doesn’t have the condition which is hugely reassuring.

It isn’t random, like population-wide testing and is going to find the disease in one in every two tests done. This means it is cost effective too.

The British Heart Foundation supports the wider introduction of cascade testing for FH.  In 2010 we funded, in partnership with the Welsh Assembly Government, an all-Wales cascade testing service for FH.  More recently we have invested just over a million pounds in funding this service at 12 sites across Scotland and England, supporting 27 specialist FH nurses over a two year period . So far, the programme has led to 1200 people being diagnosed with the genetic mutation that causes FH.  We want to see this service rolled out nationwide since no one with FH should be put at a disadvantage because of where they live.

I’m optimistic that the NHS will soon offer cascade testing across the country because we have already proven the concept and that it is safe and effective.

www.bhf.org.uk