Ischemic heart disease (IHD) is the main cause of 
death worldwide. Many factors are known to 
increase the risk of IHD. Dyslipidemia is one of the 
treatable risk factors that have polygenic and 
monogenic inheritance patterns. Familial 
hypercholesterolemia (FH) is the most common 
monogenic disorder affecting 1:100-250. It is 
estimated to affect up to 5% of patients with 
premature IHD. Dutch Lipid Clinic Network 
(DLCN), Simon Broom and Make Early Diagnosis 
to Prevent Early Death (MEDPED) criteria are 
made to establish the clinical diagnosis of FH, 
nevertheless, less than 10% of the cases with 
premature IHD are diagnosed as FH prior to 
presenting as IHD. Autosomal dominant (AD) FH 
is caused by mutations in some known genes. The 
most common causative gene is LDLR, and less 
commonly by APOB, PCSK9 and APOE genes. 
Autosomal recessive (AR) FH is caused by 
mutations in LDLRAP1, in addition to ABCG5/8
genes that cause sitosterolemia, which mimics FH. 
Genetic diagnosis is thus essential: to confirm the 
patient's diagnosis, choose the optimum lipidlowering treatment and provide cascade screening 
for the family members of affected patients