Importance of Genotype-Phenotype Correlation in the Population Screening of Familial Hypercholesterolemia

A 43-year-old male presented to our clinic with a complaint of multiple swellings on the extensor tendons of the elbows, ankles, and feet. On examination, he was found to have tendon xanthomas and xanthelasmas, and arcus lipoidosis. Investigations showed a low-density lipoprotein (LDL) level of 214 mg/dl. He had been on statins for a decade. His pretreatment LDL was 226 mg/dl. His genetic workup showed a homozygous variant in exon 9 of the low-density lipoprotein receptor (LDLR) gene of chromosome 19 and was classified as having homozygous familial hypercholesterolemia. His treatment was intensified to the maximum tolerated dosage of statin and ezetimibe but LDL was far above the acceptable limit, so he was planned for monthly injections of proprotein convertase subtilisin/kexin type 9 protein (PCSK9) inhibitor, evolocumab. Primary care physicians should have a keen eye on correlating the clinical and biochemical parameters of the patient with a genetic mutation analysis so as to not miss out on diseases with a rare occurrence such as homozygous familial hypercholesterolemia (HoFH) since early and optimal treatment with appropriate lipid-lowering therapies (LLT) is warranted to reduce the morbidity and mortality of patients. One should also increase awareness in the population for family planning due to increased maternal risk of atherosclerotic cardiovascular disease (ASCVD) during pregnancy, and also that children born to this population will have obligate heterozygous familial hypercholesterolemia (HeFH).