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Published on: September 15, 2018
Reverse cascade screening for familial hypercholesterolemia in high-risk Chinese families
Xue Wu1, Jing Pang2, Xumin Wang3
1Beijing Anzhen Hospital, Capital Medical University-Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
Insights
Reverse cascade screening effectively identifies new familial hypercholesterolemia (FH) cases in relatives of children with severe FH. This strategy diagnoses 2.8 new FH cases per proband, highlighting its diagnostic yield.
Area of Science:
- Cardiovascular Genetics
- Medical Screening
- Public Health
Background:
- Familial hypercholesterolemia (FH) is a genetic disorder leading to high LDL cholesterol.
- Reverse cascade screening is underutilized for FH detection.
- This study evaluated reverse cascade screening in families with pediatric FH probands.
Purpose of the Study:
- To assess the effectiveness of reverse cascade screening for identifying new familial hypercholesterolemia (FH) cases.
- To determine the diagnostic yield of this screening method in relatives of children with severe FH.
Main Methods:
- Reverse cascade screening was initiated from 47 index children diagnosed with severe FH (39 homozygous/compound heterozygous, 8 heterozygous).
- First- and second-degree relatives were contacted and underwent genetic screening.
- Screening involved 80 first-degree and 46 second-degree relatives for homozygous/compound heterozygous FH cases, and 17 relatives for heterozygous FH cases.
Main Results:
- All 80 first-degree relatives of homozygous/compound heterozygous FH probands were diagnosed with FH.
- 10 (12.7%) of these parents had premature coronary artery disease; none were on statins.
- 41 of 46 (89%) second-degree relatives and 12 of 17 relatives of heterozygous FH cases were diagnosed with FH, yielding 2.8 new cases per index case.
Conclusions:
- Reverse cascade screening is highly effective for diagnosing familial hypercholesterolemia (FH) in relatives of children with severe FH.
- The method successfully identifies affected first- and second-degree relatives, including those with premature cardiovascular disease.
- This strategy significantly increases the detection rate of new FH cases within families.
Background:
Reverse cascade screening is not commonly employed to detect new cases of familial hypercholesterolemia (FH). We aimed to assess the outcome of this screening strategy in families in which the probands were children with severe FH.
Hypothesis:
Reverse cascade screening is an effective method to detect new patients with FH.
Methods:
Reverse cascade screening was undertaken starting from 47 index children with severe hypercholesterolemia; 39 were homozygous/compound heterozygous FH and 8 were heterozygous FH. Available parents, siblings, and second-degree relatives were contacted and screened.
Results:
From the 39 cases of homozygous/compound heterozygous FH, 80 first-degree family members were available for screening; 70 were parents and 10 were siblings. All first-degree relatives screened were genetically diagnosed with FH. None of the parents had been treated with statins at the time of diagnosis, and 10 (12.7%) had premature coronary artery disease. Additionally, 46 second-degree relatives were screened, of which 41 (89%) were diagnosed with FH. From the 8 heterozygous FH children, 17 first- and second-degree relatives were screened and 12 new cases of FH were also diagnosed. Hence, the overall diagnostic yield of screening was 2.8 new cases of FH per index case.
Conclusions:
Reverse cascade screening is a highly effective method for diagnosing new cases of FH in parents, siblings, and second-degree relatives of index children with severe FH.
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