Dyslipidemias [31 genes]

Genetic hyperlipidemias are associated with a high predisposition to develop early atherosclerotic disease with a familial presentation, which is currently regarded as a major global health issue by the WHO. They have a high impact on cardiovascular risk, as they act from very early stages of life and constitute a factor for poor prognosis in affected patients. It has been estimated that approximately 9% of cardiac arrests in individuals younger than 65 years and up to 20% of cardiac arrests in individuals younger than 45 years are due to monogenic dyslipidemias, mainly familial hypercholesterolemia (FH). Moreover, some types of hyperlipidemia, such as severe hypertriglyceridemias, are a rare but well-documented cause of pancreatitis associated with a poor prognosis.

The nature of hyperlipidemias is very complex both at the clinical and at the genetic level. Polygenic forms of hyperlipidemia are much more common, and the manifestations of the disorder are largely influenced by environmental or secondary factors. In some forms of hyperlipidemia, the underlying genetic defect is often insufficient to cause hyperlipidemia unless additional environmental or genetic influences coexist. It is estimated that more than 60% of the variability in serum lipid levels is genetically determined, and most of this variation is due to polygenic influences. Monogenic forms of hyperlipidemia are less common and are usually clearly defined. Some of them follow a dominant inheritance pattern and are relatively common, while others are inherited in a recessive manner and are much rarer. This type of disorders is expressed independently of environmental influences.

The correct diagnosis of genetic hyperlipidemias is of great importance, since their prognosis and, therefore, the clinical management of the patient and of the family can substantially differ from those of non-genetic hyperlipidemias.

Identifying monogenic hyperlipidemias is essential, since the prognosis and, therefore, the clinical management of these patients can substantially differ from those of metabolic disorders originated by common causes (e.g. non-genetic dyslipidemias). Some of these diseases have widely variable phenotypic manifestations in certain families due to the presence of genes that modulate lipoprotein levels. Their knowledge is essential for a more accurate and personalized assessment of the risk associated with disease in members or a family.

1. Heterozygous familial hypercholesterolemia: 1:250 for most populations.
2. Homozygous familial hypercholesterolemia: 1:240,000 (estimated)
3. Autosomal recessive familial hypercholesterolemia: < 1:1,000,000
4. Sitosterolemia: < 1:1,000,000
5. Lysosomal acid lipase deficiency: 1:177,000
6. Familial chylomicronemia syndrome: 1:250,000 (estimated).
7. Transient infantile hypertriglyceridemia: < 1:1,000,000.
8. Multifactorial chylomicronemia syndrome: 1:600-1:1,000
9. Monogenic hypertriglyceridemias: 1:10-1:100
10. Familial dysbetalipoproteinemia: 1:10-1:1,000
11. Familial combined hyperlipidemia: 1:150
12. Pancreatic lipase deficiency: < 1:1,000,000

This panel is useful for the study of genetic hyperlipidemias. However, it is specifically designed for patients with mixed lipid metabolism disorders where a primary dyslipidemia is strongly suspected to be the main cause of the mixed disorder.

This panel includes genes associated with different genetic hyperlipidemias, as well as candidate genes with evidence for their association with increases in any plasma lipoproteins. It also includes variants related to polygenic hyperlipidemias. This panel also includes the LPA gene in order to identify variants in this gene associated with predisposition to high Lp(a) levels, coronary disease, and risk of cardiovascular complications.

Aimed at patients with elevated levels of several lipoproteins, who do not show hypercholesterolemia or isolated hypertriglyceridemias.