Familial Hypercholesterolemia: A Narrative Review on Diagnosis and Management Strategies for Children and Adolescents

Abstract

Familial hypercholesterolemia (FH) is a relatively common inherited disorder caused by deleterious mutation(s) in the low-density lipoprotein (LDL) receptor or its associated genes. Given its nature as a heritable disease, any useful screening scheme, including universal, and cascade screening, allows for the early identification of patients with FH. Another important aspect to note is that early diagnosis associated with appropriate treatment can promote better prognosis. However, most clinical diagnostic criteria for adults have adopted clinical elements, such as physical xanthomas and family history, both of which are usually obscure and/or difficult to obtain in children and adolescents. Moreover, LDL cholesterol levels fluctuating considerably during adolescence, hindering the timely diagnosis of FH. In addition, recent advancements in human genetics have revealed several types of FH, including conventional monogenic FH, polygenic FH caused by common single nucleotide variations (SNV) accumulation associated with elevated LDL cholesterol, and oligogenic FH with multiple deleterious genetic variations leading to substantially elevated LDL cholesterol. The aforementioned findings collectively suggest the need for amassing information related to genetics and imaging, in addition to classical clinical elements, for the accurate diagnosis of FH in this era of personalized medicine. The current narrative review summarizes the current status of the clinical and genetic diagnosis of FH in children and adolescents, as well as provide useful management strategies for FH in children and adolescents based on currently available clinical evidence.

Phenotypic vs. genetic cascade screening for familial hypercholesterolemia: A case report

“…However, children have a silent presentation of FH and phenotypic screening alone is not enough. For examination of children and adolescents, it is not often possible to identify such phenotypic markers as xanthomas, corneal arcus, arteries atherosclerotic changes, or premature cardiovascular events ( 13 , 26 ).…”

Treatment of Dyslipidaemia in Children

“…If the LDL-C goals are not attained, before adding second-line therapeutic drugs, it is possible to increase the dose of statin or switch to a more potent statin, such as rosuvastatin or atorvastatin [ 53 ]. Moreover, it is extremely important to closely monitor the adherence to treatment among patients with a poor response [ 67 ].…”

Individualized Treatment for Patients With Familial Hypercholesterolemia

“…For example, almost all patients with pediatric HeFH are asymptomatic, except for those with hyper-LDL cholesterolemia. 67 Meanwhile, adult patients with HeFH are gradually developing carotid and coronary atherosclerosis ( Fig. 3 ).…”