Familial hypercholesterolemia: one of the most common genetic diseases in France!

What is familial hypercholesterolemia?
Familial hypercholesterolemia is an autosomal dominant genetic disease, meaning that a patient has a 50/50 chance of passing the disease on to his or her child. For each gene, we inherit one allele (=version) from our mother and another from our father. This is the heterozygous form, where only one of the two alleles is affected, and is the most common form. The disease is silent and characterized by a major rise in LDL-cholesterol (=bad cholesterol) from birth. If left untreated, familial hypercholesterolemia is revealed by the onset of an early myocardial infarction, usually between the ages of 40 and 50. The homozygous form, with both alleles affected, is a rare disease affecting less than one person in a million, and reveals itself at birth. We will only discuss heterozygous familial hypercholesterolemia here.

How do I know if I'm at risk of familial hypercholesterolemia?
Because of the dominant nature of the disease, families with familial hypercholesterolemia are likely to have a history of early coronary disease (age <55 in male relatives, or <65 in female relatives) in every generation. These antecedents should be sought in first-degree relatives, i.e. parents, siblings, aunts, uncles or cousins. From a personal point of view, the occurrence of an infarction at an early age (<60 in women) is suspicious. The consequence of the genetic anomaly (mutation) is a very high LDL-cholesterol level, often in excess of 2 g/dl on fasting blood. Clinical manifestations (or symptoms) are rare, but cholesterol deposits can be seen on the joints (xanthomas) or on the cornea (corneal arc before the age of 45, otherwise common in association with cataracts). Xanthelasmas, or cholesterol deposits around the eyes, are very common in the general population and do not specifically point to this disease. Chronic exposure of the arteries to these high levels of bad cholesterol leads to the formation of atheromatous plaques, which progressively block the arteries and lead to acute vascular accidents, such as myocardial infarction. The arteries of the heart are the first to be affected by familial hypercholesterolemia.




How is familial hypercholesterolemia diagnosed?
Clinical suspicion is based on family or personal history and the presence of elevated LDL-cholesterol levels. Diagnostic confirmation relies on genetic analysis. But this is a long and difficult process, as several genes may be involved, and over 2,000 mutations have been identified to date. What's more, in 20% of cases, genetic analysis fails to identify the mutation. Genetic analysis therefore provides a diagnosis of certainty, but there are also clinical probability scores that are used routinely.
In short, genetics for whom?
- In case of LDL-cholesterol >1.6 g/dL in children or >1.9 g/dL in adults, in the presence of a personal or first-degree family history of early vascular disease.
- in case of LDL-cholesterol >1.9 g/dL in children or >2.5 g/dL in adults with no informative family history
In France, these analyses are carried out in 4 expert centers, and the results take an average of 6 months to reach the prescriber.

Why is it so important to know if you have familial hypercholesterolemia?
Early diagnosis of the disease is essential, because in the absence of cholesterol-lowering treatment, around 1 in 2 men and 1 in 3 women will suffer an early myocardial infarction. Conversely, early treatment can restore vascular risk to that of the general population. Treatment is based primarily on lowering LDL-cholesterol levels. To achieve this, statins are prescribed as the first line of treatment. This is often necessary, given the very high cholesterol levels found in patients. For women of childbearing age, it is important to know their cholesterol levels and to ask their partner about a family history of vascular disease, in order to identify a potential risk for the unborn child and to set up appropriate early screening. Familial hypercholesterolemia has no effect on pregnancy, and in most cases, treatment can be suspended for the duration of pregnancy and breast-feeding, without any consequences for the mother. This is discussed with the specialist on a case-by-case basis. In view of the frequency and potential seriousness of this disease, the question is currently being raised of systematic general screening by means of LDL-cholesterol measurement before the age of 9.
The mission of the Agir nouveau pour le Cœur des Femmes endowment fund is to alert, anticipate and support women in the detection and management of familial hypercholesterolemia.