Christian Susan, Atallah Joseph, Clegg Robin, Giuffre Michael, Huculak Cathleen, Dzwiniel Tara, Parboosingh Jillian, Taylor Sherryl, Somerville Martin
Department of Medical Genetic, University of Alberta, 826 Medical Sciences Building, Edmonton, AB, T6G 2H7, Canada.
Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
J Genet Couns. 2018 Feb;27(1):124-130. doi: 10.1007/s10897-017-0129-0. Epub 2017 Jul 11.
Predictive genetic testing in minors should be considered when clinical intervention is available. Children who carry a pathogenic variant for an inherited arrhythmia or cardiomyopathy require regular cardiac screening and may be prescribed medication and/or be told to modify their physical activity. Medical genetics and pediatric cardiology charts were reviewed to identify factors associated with uptake of genetic testing and cardiac evaluation for children at risk for long QT syndrome, hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. The data collected included genetic diagnosis, clinical symptoms in the carrier parent, number of children under 18 years of age, age of children, family history of sudden cardiac arrest/death, uptake of cardiac evaluation and if evaluated, phenotype for each child. We identified 97 at risk children from 58 families found to carry a pathogenic variant for one of these conditions. Sixty six percent of the families pursued genetic testing and 73% underwent cardiac screening when it was recommended. Declining predictive genetic testing was significantly associated with genetic specialist recommendation (p < 0.001) and having an asymptomatic carrier father (p = 0.006). Cardiac evaluation was significantly associated with uptake of genetic testing (p = 0.007). This study provides a greater understanding of factors associated with uptake of genetic testing and cardiac evaluation in children at risk of an inherited arrhythmia or cardiomyopathy. It also identifies a need to educate families about the importance of cardiac evaluation even in the absence of genetic testing.
当有临床干预措施时，应考虑对未成年人进行预测性基因检测。携带遗传性心律失常或心肌病致病变异的儿童需要定期进行心脏筛查，可能会被开处方药和/或被告知调整体育活动。回顾了医学遗传学和儿科心脏病学图表，以确定与长QT综合征、肥厚型心肌病或致心律失常性右室心肌病高危儿童接受基因检测和心脏评估相关的因素。收集的数据包括基因诊断、携带致病基因的父母的临床症状、18岁以下子女数量、子女年龄、心脏骤停/死亡家族史、心脏评估的接受情况，以及如果进行了评估，每个孩子的表型。我们从58个家庭中确定了97名高危儿童，这些家庭被发现携带上述其中一种疾病的致病变异。66%的家庭进行了基因检测，73%在被建议时接受了心脏筛查。拒绝预测性基因检测与遗传专家的建议（p<0.001）和父亲为无症状携带者（p=0.006）显著相关。心脏评估与基因检测的接受情况显著相关（p=0.007）。本研究有助于更深入了解与遗传性心律失常或心肌病高危儿童接受基因检测和心脏评估相关的因素。它还表明，即使在没有进行基因检测的情况下，也有必要对家庭进行心脏评估重要性的教育。
