KCNQ1 Cascade Screening

Study Overview
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Brief Summary
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The objectives of the protocol are to: (1) evaluate the uptake of cascade screening and preventative therapies after the implementation of a simplified screening process and (2) assess proband and family member perspectives about the return of research results and cascade screening for the KCNQ1 Thr224Met variant. The investigators will conduct a mixed methods study in the Old Order Amish community where the KCNQ1 variant is enriched over 100,000-fold compared to other populations. The intervention will offer free, mail-in, saliva-based genetic testing for family members of probands. The rate of uptake of testing and preventative therapy after the intervention is implemented (i.e. when 'simplified' free, mail-in, saliva-based testing was available) will be compared to data from before the intervention (i.e. when 'traditional' $50 blood-based testing was available to family members) when uptake was essentially zero. The primary outcome is the rate of uptake of cascade screening with the intervention ('simplified'). The secondary outcomes include: extent of disclosure of genotype results before and after the intervention, proportion of informed relatives who get screened before and after the intervention, and the uptake of appropriate preventative care (e.g. seeing a cardiologist and/or taking beta-blocker). The tertiary outcomes are demographic characteristics associated with uptake of cascade screening or uptake of preventative therapy. The investigators will also assess qualitative themes surrounding the return of results process and cascade screening using interviews.

Official Title
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A Community-Based Approach to Overcoming Barriers to Cascade Screening for Long QT Syndrome

Conditions
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Long QT Syndrome

Intervention / Treatment
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* Genetic: Simplified Cascade Screening


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: KCNQ1Thr224Met proband or first degree family member Exclusion Criteria: Family members who have not been contacted by probands
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Simplified Cascade Screening<br>Free, mail-in, saliva-based screening for the KCNQ1 Thr224Met variant. | Genetic: Simplified Cascade Screening<br>* Screening of the KCNQ1 Thr224Met variant for family members of probands<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of At-risk Family Members Who Underwent Cascade Screening | Rate of uptake of cascade screening after the intervention ('simplified') | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extent of Disclosure Determined by Questionnaire | proportion of family members told after the intervention ('simplified') | 18 months | 
| Number of Informed Relatives Screened Determined by Questionnaire | Number of informed family members tested after the intervention ('simplified') | 18 months | 
| Number of Participants With an Uptake of Preventative Therapy as Determined by Questionnaire | Uptake of preventative therapy was defined as those taking a beta-blocker if recommended or those who implemented lifestyle modifications if beta-blocker not recommended. The survey was mailed to all probands. | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cascade, Screening, Ethical, Legal, Social