IllnessArteriosclerosis, monogenic; differential diagnosis

NGS +

[Sanger]

In arteriosclerosis, deposits of fat, cholesterol and additional substances form plaque in the inner walls of arteries. Plaque increases the risk of blood clotting, heart attack and stroke. The risk of developing atherosclerosis can be influenced by heredity. Almost all forms of arteriosclerosis are caused by a complex interaction of many genes and other (environmental) influences. The association between elevated serum cholesterol, triglyceride and lipoprotein levels with increased risk for atherosclerotic cardiovascular disease has been documented in guideline-like, international publications. Additional monogenic conditions such as general arterial calcification cause very rarely arteriosclerosis. The monogenic inheritance patterns are autosomal dominant, rarely recessive. A negative molecular genetic finding excludes the clinical diagnosis by no means.

References: https://www.thelancet.com/action/showPdf?pii=S2213-8587%2819%2930264-5

https://www.acc.org/Latest-in-Cardiology/Articles/2020/11/13/20/26/Genetic-Testing-for-Managing-Dyslipidemia

• DD: Hypercholesterolaemia, familial, 2; allelic heterogeneity: Hypo-/Abetalipoproteinemia
• Allelic: Cole disease (ENPP1)
• Allelic: Diabetes mellitus, non-insulin-dependent, susceptibility to (ENPP1)
• Allelic: HDL deficiency, familial, 1 (ABCA1)
• Allelic: Hypobetalipoproteinemia (APOB)
• Allelic: Hypophosphatemic rickets, AR, 2 (ENPP1)
• Allelic: Low density lipoprotein cholesterol level QTL 1 (PCSK9)
• Allelic: Low density lipoprotein cholesterol level QTL2 (LDLR)
• Allelic: Obesity, susceptibility to (ENPP1)
• Allelic: Pseudoxanthoma elasticum (ABCC6)
• Allelic: Pseudoxanthoma elasticum, forme fruste (ABCC6)
• Allelic: Tangier disease, disorders of high density lipoprotein metabolism (ABCA1)
• Allelic: Wolman disease [fulminant infant disease, massive liver/spleen infiltration] (LIPA)
• Arterial calcification, generalized, of infancy, 1 (ENPP1)
• Arterial calcification, generalized, of infancy, 2 (ABCC6)
• Calcification of joints and arteries (NT5E)
• Cholesteryl ester storage disease (LIPA)
• Guttate hypopigmentation, punctate palmoplatar keratoderma +/- ectopic cxalcification (ENPP1)
• Hypercholesterolemia, familial, 1 (LDLR)
• Hypercholesterolemia, familial, 2 (APOB)
• Hypercholesterolemia, familial, 3 (PCSK9)
• Hypercholesterolemia, familial, 4 (LDLRAP1)