HRS Board Review 2025 New Courses (Reviewers Copy)-Workshop 1_Electrocardio_London_2025

Video Transcription

The answer is C, Joe's brother should be tested using a long QT gene panel. Joe and his children should only be tested if a gene is identified.  So genetic testing for an unknown mutation has potential clinical benefit. It can direct clinical follow-up in the family.  It can be done using gene panels or using whole exome sequencing limited to the known genes that are affected in the disorder.  For genotype positive individuals, even if they are asymptomatic, there is potential benefit. Affected individuals can be told to avoid drugs that may exacerbate the condition.  There is also the use of primary prevention therapy, the most common example of which is the use of beta blockers in long QT syndrome, especially long QT type 1.  Now initial genetic testing should always be done in a definitively affected individual so that one knows that one is genetically testing an affected person.  This is important because the sensitivity of genetic testing is only about 50 to 60% in most of the inherited arrhythmia syndromes.  So the testing isn't good enough to pick up all of the affected individuals, to identify a gene and a mutation in all of the affected individuals.  If a causative mutation is identified, cascade screening of first-degree relatives and anyone else in the family who is clinically suspicious should be done.  So first-degree relatives of the affected person are tested, and then first-degree relatives  of any new identified affected individuals are tested, and one marches through the family. However, anyone who is clinically suspicious anywhere in the family should then be tested.  If a causative mutation in any affected individual is not found, then there's no reason to do further clinical genetic testing on anyone else in the family.  Now whole exome sequencing does have the ability to identify new genes, but that is not clinical genetic testing. That would be a research study.  Finally, Joe's brother clinically has Long QT syndrome. Joe, who is clinically unaffected, may carry the Long QT gene, an example of incomplete penetrance, or he may not.  He may be genotypically normal.

Video Summary

Genetic testing for Long QT syndrome should start with an affected individual using a gene panel. If a mutation is found, family members can be tested to identify those at risk. Testing has a clinical benefit, guiding follow-up and prevention strategies like avoiding certain drugs and using beta blockers for type 1. It begins with affected individuals due to the 50-60% sensitivity of tests. Cascade screening of relatives follows if a mutation is identified. Whole exome sequencing may identify new genes but is not used clinically. Joe's brother shows clinical symptoms, but Joe could be a carrier or unaffected.

Keywords

Long QT syndrome

genetic testing

cascade screening

mutation identification

clinical prevention