Building a family network from genetic testing

Abstract

BackgroundGenetic testing has multigenerational and familial repercussions. However, the “trickle‐down effect” of providing genetic counseling and testing to family members at risk after an initial identification of a pathogenic variant in a medically actionable gene has been poorly understood.MethodsThree probands were identified during the pharmacogenetics research phase of eMERGEII (electronic MEdical Record and Genomics, phase II) to have variants in genes associated with autosomal dominant adult‐onset disorders determined to be actionable by the American College of Medical Genetics (ACMG). Two of the three probands had variants that were classified as pathogenic and the third proband had a variant ultimately classified of uncertain significance, but of concern due to the proband's own phenotype. All probands had additional family members at risk for inheriting the variant. Two of the three probands had family members who received their medical care from the same health care system, Group Health Cooperative (GHC). It was recommended that the proband contact their family members at risk to be referred to genetic counseling for consideration of genetic testing.ResultsThe two probands with pathogenic variants contacted some of their family members at risk. Individuals contacted included children and adult grandchildren, particularly if they received their medical care at GHC. To the best of our knowledge, siblings and more distant relatives at risk were not informed by the proband of their genetic risk.ConclusionsEstablishing a family network is essential to disseminate knowledge of genetic risk. These three initial cases describe our experience of contacting eMERGE participants with identified variants, providing the probands with appropriate genetic counseling and care coordination, and recommendations for contacting family members at risk. Greater challenges were observed for coordinating genetics care for family members and extending the family network to include other relatives at risk.

A systematic literature review of disclosure practices and reported outcomes for medically actionable genomic secondary findings

“…Seven articles did not report any outcome data. Four articles described panel-based sequencing efforts 23 , 24 , 27 , 28 . See Table 3 for additional characteristics of the included articles.…”

“…Seventeen articles described the specific personnel involved in the disclosure of a SF to a total of 618 SF recipients 4 , 23 , 25 , 27 , 30 – 34 , 36 – 43 . Genetic counselors and medical geneticists were the disclosing providers in ten articles 4 , 23 , 31 , 32 , 34 , 36 , 39 – 42 and three additional articles described a team approach to disclosure which included personnel with genetics expertise 25 , 27 , 38 . A cardiology nurse disclosed cardiac-related SF to 23 participants in a Finnish biobank 30 .…”

“…A Finnish biobank followed a similar procedure for their participants; notification letters were sent to 23 individuals with cardiac-related SF and then a cardiology nurse followed up with each individual by phone 30 . In ten additional articles describing how SF were disclosed to 73 individuals or families, disclosures were most often made in-person during a clinic visit although several articles reported that some disclosures were made by telephone 4 , 25 , 27 , 31 , 32 , 34 , 36 , 38 , 43 – 45 .…”

“…Twenty-two articles describing SF disclosure to 646 SF recipients explicitly mentioned that SF recipients were provided with recommendations for management and/or referrals for additional care related to their SF 1 , 4 , 21 , 22 , 24 – 28 , 30 – 34 , 36 – 38 , 40 , 42 , 44 – 46 . Twelve articles described recommending that SF recipients notify their families about their results so that relatives could consider cascade testing 22 , 24 , 25 , 27 , 28 , 31 – 33 , 36 – 38 . Several single family reports described how cascade testing of relatives was facilitated by the disclosing providers or team 25 , 27 , 37 , 45 .…”

“…Twelve articles described recommending that SF recipients notify their families about their results so that relatives could consider cascade testing 22 , 24 , 25 , 27 , 28 , 31 – 33 , 36 – 38 . Several single family reports described how cascade testing of relatives was facilitated by the disclosing providers or team 25 , 27 , 37 , 45 .…”