A Case Report: Two Young Children with Long QT Syndrome Type-2 Diagnosed by Presymptomatic Genetic Testing

Long QT syndromes (LQTSs) can lead to sudden cardiac death, yet these syndromes are often asymptomatic and clinically undetected, despite the prolongation of the QT interval. Currently, when a disease-causing variant is identified in an individual, presymptomatic genetic testing is available and can form part of the recommended cascade testing to identify other family members at risk. We herein report the cases of two daughters who received presymptomatic genetic testing in infancy when the proband mother had been diagnosed with LQTS type 2 (LQT2; c.1171C > T, p.Q391X in KCNH2) after suffering from cardiac arrhythmia at 30 years of age. The daughters had a normal QTc interval, but they carried the same disease-causing variant as their mother. Children with family members who have genetically confirmed LQTS have a high risk of suffering from cardiac events later in life, so genetic testing is required. This poses a complex problem, as guidelines for medical intervention and follow-up systems among asymptomatic children with LQTS have yet to be established. Genetic testing should only be performed after adequate counseling to support children later in life. Individualized long-term genetic counseling is required for both parents and children at stages throughout life.

Human Genetics Society of Australasia Position Statement: Predictive and Presymptomatic Genetic Testing in Adults and Children

In 2020, the Human Genetics Society of Australasia released its Position Statement on Predictive and Presymptomatic Genetic Testing in Adults and Children. This Position Statement synthesizes the major practical, psychosocial and ethical considerations associated with presymptomatic and predictive genetic testing in adults who have the capacity to make a decision, children and young people who lack capacity and adults living with reduced or fluctuating capacity. Recommendations include that predictive testing in adults, young people and children should only be offered with pretest genetic counseling and the option of posttest genetic counseling. An individual considering (for themselves or on behalf of another) whether to have a predictive test should also be supported to allow them to make an autonomous and informed decision. Predictive testing should only be offered to children and young people for conditions where there is likely to be a direct medical benefit to them through surveillance, use of prevention strategies or other medical interventions in the immediate future. Where symptoms are likely to develop in childhood, in the absence of options to implement surveillance or risk reduction measures, genetic health professionals and parents/guardians should discuss whether undertaking predictive testing is the best course of action for the child and the family as a whole. Where symptoms are likely to develop in adulthood, the default position should be to postpone predictive testing until the young person achieves the capacity to make their own autonomous and informed decision.

Public Willingness to Undergo Presymptomatic Genetic Testing for Alzheimer’s Disease

Presymptomatic genetic testing (PGT) for Alzheimer’s disease (AD) is available for at-risk individuals. This study aimed to investigate the public perception of PGT in Saudi Arabia and determine variables that might influence the decision to undergo PGT. A questionnaire link was posted on Twitter by the Saudi Alzheimer’s Disease Association and was made publicly available on social media networks. A total of 2935 people participated, of which 59.9% were willing to undergo PGT. Of these, 26.8% reported having a family history of AD, and 0.24% had two family members with early onset AD. The reasons cited for willingness to undergo PGT included the following: to adopt a healthier lifestyle, to ensure appropriate family and financial planning, to seek early treatment, and to relieve anxiety. In multiple logistic regression analysis, willingness to undergo PGT was negatively associated with having a self-reported family history of dementia (OR 0.81, 95% CI 0.68-0.96) and was positively associated with marital status (OR 1.39, 95% CI 1.13-1.70). In conclusion, PGT for AD seems to be well accepted in this large Saudi cohort. The reasons cited are similar to those reported elsewhere in the literature.