Familial Hypercholesterolemia: Cascade Screening in Children and Relatives of the Affected
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Familial Hypercholesterolemia (FH) is an inherited disorder of lipid metabolism characterized by very high low density lipoprotein (LDL) cholesterol since birth, resulting in premature atherosclerosis and coronary artery disease (CAD). Cascade screening of children and family members of proven FH individuals can identify more subjects who have high LDL cholesterol or the family mutation and appropriate intervention can reduce their risk of atherosclerosis and prevent its complications.
Cascade screening by molecular testing, was carried out in 133 family members, comprising 24 children, of 31 probands with FH having a pathogenic mutation in LDLR/ApoB gene. Lipid profiles were obtained in 44 family members including 11 children.
Of 133 family members tested, 88 (66.1%) were identified to carry the family mutation. Twelve of these were children below 18 y of age and 76 were adults. CAD was present in 15 (11.2%) family members and 63(47.4%) family members, including nine children, were already on Lipid Lowering Therapy.
Cascade screening led to identification of 88 new cases, with a pathogenic mutation, who were at a very high risk of developing premature CAD. The authors identified 12 children with family specific mutation, out of which 9 were initiated on low dose statin therapy. Four homozygous children were treated with high dose statins because of substantially increased risk of CAD. Cascade screening, therefore, proved to be a successful initiative towards primary prevention of CAD in India.
KeywordsFamilial hypercholesterolemia Cascade screening Children Genetic testing
The authors acknowledge the cardiologists and physicians from various states of India for referring the cases to Institute of Medical Genetics and Genomics, Sir Ganga Ram hospital, New Delhi. They are thankful to all their patients and family members for providing them with important information and blood samples for genetic studies. The authors extend their thanks to SGRH and ICMR for financial assistance.
ICV was involved in conceiving the idea, initial study design and critical evaluation of the manuscript. RS helped with study design, technical troubleshooting and manuscript evaluation. JPS was involved in patient referrals and management. NS was involved in data acquisition, molecular studies, data analysis and manuscript preparation. ICV will act as guarantor for this paper.
Compliance with Ethical Standards
Conflict of Interest
Source of Funding
The study has been funded by Research Development Program, Sir Ganga Ram Hospital (Grant No: EC/10/10/197; 4.9.13) and Indian Council of Medical Research (Sanction No: 54/16/2011-BMS).
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