When is genetic testing recommended for FH? 

In the UK, genetic testing for Familial Hypercholesterolaemia (FH) is recommended when a patient meets specific clinical criteria indicating a high probability of an inherited lipid disorder. This usually occurs if an adult has an LDL cholesterol level above 4.9 mmol/L or if there is a strong family history of early heart disease. Once a genetic mutation is identified in one person, testing is then recommended for all biological relatives through a process known as cascade testing. 

What We’ll Discuss in This Article 

• The specific cholesterol thresholds that trigger genetic investigation. 

• Using the Simon Broome and Dutch Lipid Clinic Network (DLCN) scores. 

• When children with a family history should be offered a DNA test. 

• The role of physical signs, such as tendon xanthomas, in the referral process. 

• How ‘cascade testing’ works for first-degree relatives. 

• The importance of identifying the index case in a family. 

• Next steps if you meet the criteria for a specialist lipid clinic referral. 

Clinical Thresholds for Testing 

Genetic testing is not a first-line test for everyone with high cholesterol. It is reserved for those whose lipid levels are significantly higher than the general population. In the UK, clinicians use the Simon Broome or DLCN criteria to decide who should be referred for DNA analysis. 

A referral for genetic testing is typically recommended if an individual has: 

• A Total Cholesterol level above 7.5 mmol/L (Adults) or 6.7 mmol/L (Children). 

• An LDL Cholesterol level above 4.9 mmol/L (Adults) or 4.0 mmol/L (Children). 

Source:https://assets.publishing.service.gov.uk/media/5b646bbced915d37793abcda/familial_hypercholesterolaemia_implementation_guide.pdf 

The Simon Broome and DLCN Scoring Systems 

To standardise when genetic testing is offered, the NHS uses validated scoring systems. These systems look at your cholesterol levels, your personal medical history, and your family’s history of cardiovascular events. 

The Dutch Lipid Clinic Network (DLCN) Score 

The DLCN score assigns points for different findings. Genetic testing is usually recommended if a patient scores 5 or higher (Possible FH) or 8 or higher (Definite FH). 

Category	Finding	Points
Cholesterol Level	LDL above 8.5 mmol/L	8
Physical Signs	Tendon Xanthomas (swollen tendons)	6
Personal History	Premature heart disease (Men <55, Women <60)	2
Family History	1st-degree relative with early heart disease	1

When Children Should Be Tested 

In families with a known FH mutation, testing children early is a clinical priority in the UK. This allows for early lifestyle intervention and the introduction of treatment before any damage to the arteries occurs. 

Current NICE (National Institute for Health and Care Excellence) 2026 guidance recommends: 

• If a parent has a confirmed FH mutation, the child should ideally be tested by age 10. 

• If both parents have FH, testing should happen as early as possible (sometimes by age 2) to check for the rare and more severe homozygous form of the condition. 

Cascade Testing for Relatives 

Once a genetic mutation is found in a family member (the ‘index case’), the NHS recommends cascade testing. This is a systematic process of identifying and testing all biological relatives. 

• First-degree relatives: Parents, siblings, and children of the index case are offered a genetic test immediately. 

• Extended family: If a first-degree relative tests positive, the process cascades further to their own children and siblings. 

This method is highly effective because each first-degree relative has a 50% chance of having the same condition. By testing relatives of known patients, the NHS can find individuals with high cholesterol who might otherwise go undiagnosed until they experience a heart attack. 

Causes and Triggers for Specialist Referral 

While the underlying cause of FH is a genetic mutation present from birth, certain clinical triggers will prompt a doctor to move from standard management to a genetic referral. 

• Lack of Response to Treatment: If a patient’s LDL levels remain very high despite maximum-dose statins, it triggers a suspicion of an underlying genetic cause. 

• Physical Findings: The discovery of corneal arcus (a white ring around the eye) in someone under age 45 or xanthomas (fatty lumps) on the knuckles or Achilles tendon. 

• Premature Cardiac Events: If a patient or their close relative has a heart attack at an unusually young age, this is a major trigger for genetic screening. 

Differentiation: Clinical vs. Genetic Diagnosis 

It is important to understand the difference between a clinical diagnosis and a genetic confirmation. 

Feature	Clinical Diagnosis	Genetic Confirmation
Basis	Based on cholesterol levels and signs.	Based on finding a DNA mutation.
Certainty	Considered ‘Probable’ or ‘Possible’.	Considered ‘Definite’.
Family Impact	Family history is noted.	Triggers formal cascade testing.
Availability	Done by a GP.	Done by a specialist Lipid Clinic.

To Summarise 

Genetic testing for FH is recommended when an individual has significantly elevated LDL cholesterol or a strong family history of early heart disease, typically meeting the Simon Broome or DLCN thresholds. Once an index case is confirmed, cascade testing is offered to all first-degree relatives to ensure early diagnosis. For children in affected families, testing is ideally recommended by age 10. These tests are essential for providing a definite diagnosis and preventing premature cardiovascular events. 

If you experience sudden chest pain, shortness of breath, or sudden weakness in the face or limbs, call 999 immediately. 

Authority Snapshot 

Dr. Rebecca Fernandez is a UK-trained physician with an MBBS and experience in general surgery, cardiology, internal medicine, gynecology, intensive care, and emergency medicine. She has managed critically ill patients, stabilised acute trauma cases, and provided comprehensive care across inpatient and outpatient settings. This guide is based on 2026 clinical standards from the NHS and NICE to ensure the public receives accurate information regarding genetic testing for inherited conditions.