Abstract 017: Clinical Utility Of Genetic Testing For Familial Hypercholesterolemia In A Pediatric Dyslipidemia Clinic

Abstract

Background: Familial hypercholesterolemia (FH) in children is diagnosed by identification of a known FH pathogenic variant or clinical criteria. We sought to determine the number of pediatric probands undergoing genetic testing for FH that met clinical criteria, and to evaluate differences between genotype positive and negative probands. Methods: All children ≤18 years old undergoing genetic testing for suspected FH were included. Clinical FH was defined as LDL ≥160 mg/dL and family history of premature CAD in 1 st /2 nd degree relatives. Screening of 1 st /appropriate 2 nd degree family members was recommended at all visits (lipid panel or genetic test) and was complete if obtained within 1 year of proband testing. Probands were stratified based on the presence or absence of known FH pathogenic variants. Wilcoxon rank sum or chi-squared tests compared lipid panel, LP(a), BMI percentile, number of screening tests performed, and family members diagnosed with FH. Results: Of 76 probands (age 12.5±2.9 years, 57% males) with suspected FH and genetic testing; 41 (54%) were genotype positive. Genotype positive probands were more likely to meet clinical criteria (44% vs. 17%, p=0.01), but only 19/41 (46%) had a positive family history. Genotype positive probands had higher total cholesterol (mg/dL) [median (IQR): 260 (242-297) vs. 226 (215-245), p<0.01] and LDL [199 mg/dL (174-229) vs. 153 mg/dL (144-171), p<0.01]. Sex, BMI percentile, family history, HDL, triglycerides, and LP(a) were similar between groups. Genotype positive probands (adopted probands excluded) had more screening tests performed [median (IQR): 4 (2-6) vs. 2 (1-3), p<0.01] and more new family members identified [3 (1-4) vs. 0 (0-1), p<0.01]. Conclusion: Clinical criteria alone underdiagnosed FH in children and a negative family history occurred in over half of pediatric FH patients. A positive genetic diagnosis increased the number of screening tests performed and improved identification of at-risk family members. Therefore, genetic testing should be performed in all suspected pediatric FH patients.