Quality statement 5: Cascade testing

Quality statement

Relatives of people with a confirmed diagnosis of monogenic familial hypercholesterolaemia (FH) are offered DNA testing through a nationwide, systematic cascade process.

Rationale

Most people in the UK with FH are undiagnosed. Cascade testing has been shown to be effective for identifying people with FH, especially when provided nationwide. Nationwide cascade testing ensures that all family members can access DNA testing wherever they live.

Quality measures

Structure

Evidence of local arrangements to ensure that relatives of people with a confirmed diagnosis of monogenic FH are offered DNA testing through a nationwide systematic cascade processes.

Data source: Local data collection.

Process

a) Proportion of untested first‑degree relatives of people with a confirmed diagnosis of monogenic FH who are offered cascade testing.

Numerator – The number of people in the denominator offered cascade testing.

Denominator – The number of untested first‑degree relatives of people with a confirmed diagnosis of monogenic FH.

Data source: Local data collection using a dedicated database.

b) Proportion of at‑risk, untested, second‑ and third‑degree relatives of people with a confirmed diagnosis of monogenic FH who are offered cascade testing.

Numerator – The number of people in the denominator offered cascade testing.

Denominator – The number of at‑risk, untested second‑ and third‑degree relatives of people with a confirmed diagnosis of monogenic FH.

Data source: Local data collection using a dedicated database.

c) Proportion of untested first‑degree relatives of people with a confirmed diagnosis of monogenic FH who receive cascade testing.

Numerator – The number of people in the denominator receiving cascade testing.

Denominator – The number of untested first‑degree relatives of people with a confirmed diagnosis of monogenic FH.

Data source: Local data collection using a dedicated database.

d) Proportion of at‑risk, untested, second‑ and third‑degree relatives of people with a confirmed diagnosis of monogenic FH who receive cascade testing.

Numerator – The number of people in the denominator receiving cascade testing.

Denominator – The number of at‑risk, untested second‑ and third‑degree relatives of people with a confirmed diagnosis of monogenic FH.

Data source: Local data collection using a dedicated database.

Outcome

Prevalence of FH.

Data source: Local data collection using a dedicated database.

What the quality statement means for service providers, healthcare practitioners, and commissioners

Service providers ensure that systems are in place for relatives of people with a confirmed diagnosis of monogenic FH to be offered DNA testing through a nationwide, systematic cascade process.

Specialists with expertise in FH offer DNA testing to relatives of people with a confirmed diagnosis of monogenic FH through a nationwide, systematic cascade process.

Commissioners ensure that they commission services that offer DNA testing to relatives of people with a confirmed diagnosis of monogenic FH, through a nationwide, systematic cascade process.

What the quality statement means for patients, service users and carers

Relatives of people with a confirmed diagnosis of FH and a known DNA mutation are offered DNA testing themselves as part of a national scheme.

Source guidance

Familial hypercholesterolaemia: identification and management (NICE guideline CG71), recommendation 1.2.1

Definitions of terms used in this quality statement

Familial hypercholesterolaemia (FH)

FH relates to heterozygous FH only.

Monogenic FH

Present when an autosomal dominant pattern of inheritance of elevated LDL‑C levels is seen in the extended family of the proband (for example, on average 50% of first‑degree relatives have elevated levels). In relatives, the age‑ and gender‑specific diagnostic cut‑offs in NICE's guideline on familial hypercholesterolaemia should be used because the Simon Broome diagnostic cut‑offs are not appropriate for relatives. The diagnosis of monogenic FH can also be given when the index case carries a documented FH‑causing mutation in the LDLR, APOB or PCSK9 genes.

Confirmed diagnosis of monogenic FH

This requires evidence from DNA testing of an FH‑causing mutation in the LDLR, APOB or PCSK9 genes. Before cascade testing is initiated in relatives, a diagnosis of monogenic FH in the index person should be confirmed by a specialist with expertise in FH.

Relatives

At least first‑ and second‑degree biological relatives and third‑degree biological relatives if possible, as defined in the glossary for NICE's guideline on familial hypercholesterolaemia.

Cascade testing

A mechanism for identifying people at risk of a genetic condition by a process of family tracing. For FH the test employed is a DNA test where a disease-causing mutation has been identified in the index individual/proband.