Attitudes toward returning pathogenic KCNQ1 variant and uptake of cascade screening in the Amish

To assess the experience of Amish regarding return of results (RoR) of long QT syndrome founder variant KCNQ1 p.(Thr224Met), information sharing, and uptake of beta-blockers, and variant testing in at-risk family members (cascade testing).

Probands (n = 88) with KCNQ1 p.(Thr224Met), previously identified by exome sequencing, after RoR, were mailed: (1) survey on attitudes toward RoR and (2) response card indicating interest in free, in-home cascade testing of first-degree relatives, indicating contact preference by study team (direct contact) or proband. Participant recall of beta blocker recommendation was compared with notes from RoR counseling.

Surveys were received from 33 of 88 (37.5%) participants. Positive perceptions of the utility of genetic testing were reported (mean = 32.1, SD = 3.4, range 25-38). Of 23 respondents recalling that a beta blocker was recommended, 4 (17.4%) were taking one. Cascade testing interest responses were received from 69 of 88 (78%) participants; 25 expressed interest in cascade testing of children or information for family members. Most participants chose direct contact (90%). Seventy-nine family members (63 children, 16 siblings) from 18 families were tested, all through direct contact.

The RoR process was well received, although uptake of beta blockers was low. Cascade testing interest was modest; however, most followed through on testing. These results help to inform strategies to improve cascade testing in this population.