Department of Cardiology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
Vasc Health Risk Manag. 2021 Feb 17;17:59-67. doi: 10.2147/VHRM.S266249. eCollection 2021.
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.
家族性高胆固醇血症（FH）是一种相对常见的遗传性疾病，由低密度脂蛋白（LDL）受体或其相关基因的有害突变引起。鉴于其遗传性疾病的性质，任何有用的筛查方案，包括普遍筛查和级联筛查，都可以早期识别 FH 患者。另一个需要注意的重要方面是，早期诊断和适当的治疗可以促进更好的预后。然而，大多数成人临床诊断标准都采用了临床元素，如身体黄瘤和家族史，这些元素在儿童和青少年中通常是模糊的和/或难以获得的。此外，青春期 LDL 胆固醇水平波动较大，阻碍了 FH 的及时诊断。此外，人类遗传学的最新进展揭示了几种 FH 类型，包括传统的单基因 FH、由与 LDL 胆固醇升高相关的常见单核苷酸变异（SNV）积累引起的多基因 FH，以及多个有害遗传变异导致 LDL 胆固醇显著升高的寡基因 FH。上述发现共同表明，在个性化医疗时代，除了经典的临床元素外，还需要积累与遗传学和影像学相关的信息，以便准确诊断 FH。本综述总结了目前儿童和青少年 FH 的临床和遗传诊断现状，并根据目前可用的临床证据，为儿童和青少年 FH 提供了有用的管理策略。
