title: Not the End of the Odyssey: Parental Perceptions of Whole Exome Sequencing (WES) in Pediatric Undiagnosed Disorders.
abstract: Due to the lack of empirical information on parental perceptions of primary results of whole exome sequencing (WES), we conducted a retrospective semi-structured interview with 19 parents of children who had undergone WES. Perceptions explored during the interview included factors that would contribute to parental empowerment such as: parental expectations, understanding of the WES and results, utilization of the WES information, and communication of findings to health/educational professionals and family members. Results of the WES had previously been communicated to families within a novel framework of clinical diagnostic categories: 5/19 had Definite diagnoses, 6/19 had Likely diagnoses, 3/19 had Possible diagnosis and 5/19 had No diagnosis. All parents interviewed expressed a sense of duty to pursue the WES in search of a diagnosis; however, their expectations were tempered by previous experiences with negative genetic testing results. Approximately half the parents worried that a primary diagnosis that would be lethal might be identified; however, the hope of a diagnosis outweighed this concern. Parents were accurately able to summarize their child's WES findings, understood the implications for recurrence risks, and were able to communicate these findings to family and medical/educational providers. The majority of those with a Definite/Likely diagnosis felt that their child's medical care was more focused, or there was a reduction in worry, despite the lack of a specific treatment. Irrespective of diagnostic outcome, parents recommended that follow-up visits be built into the process. Several parents expressed a desire to have all variants of unknown significance (VUS) reported to them so that they could investigate these themselves. Finally, for some families whose children had a Definite/Likely diagnosis, there was remaining frustration and a sense of isolation, due to the limited information that was available about the diagnosed rare disorders and the inability to connect to other families, suggesting that for families with rare genetic disorders, the diagnostic odyssey does not necessarily end with a diagnosis. Qualitative interviewing served a meaningful role in eliciting new information about parental motivations, expectations, and knowledge of WES. Our findings highlight a need for continued communication with families as we navigate the new landscape of genomic sequencing.
authors: Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Box 103757, Durham, NC, 27710, USA. allyn.mcconkie@duke.edu.
authors: Allyn McConkie
authors: AM
authors: Rosell
authors: Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Box 103757, Durham, NC, 27710, USA.
authors: Loren D M
authors: LD
authors: Pena
authors: Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Box 103757, Durham, NC, 27710, USA.
authors: Kelly
authors: K
authors: Schoch
authors: Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Box 103757, Durham, NC, 27710, USA.
authors: Rebecca
authors: R
authors: Spillmann
authors: Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Box 103757, Durham, NC, 27710, USA.
authors: Jennifer
authors: J
authors: Sullivan
authors: Department of Allied Health, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors: Stephen R
authors: SR
authors: Hooper
authors: Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Box 103757, Durham, NC, 27710, USA.
authors: Yong-Hui
authors: YH
authors: Jiang
authors: Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Box 103757, Durham, NC, 27710, USA.
authors: Nicolas
authors: N
authors: Mathey-Andrews
authors: Institute for Genomic Medicine, Columbia University Medical Center, New York, NY, USA.
authors: David B
authors: DB
authors: Goldstein
authors: Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Box 103757, Durham, NC, 27710, USA.
authors: Vandana
authors: V
authors: Shashi
mesh_terms: D000328:Adult; D003142:Communication; D030881:Disclosure; D059472:Exome; D005260:Female; D030342:Genetic Diseases, Inborn / Q000175:diagnosis*; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009042:Motivation; D010290:Parents / Q000523:psychology*; D010372:Pediatrics; D035583:Rare Diseases / Q000175:diagnosis / Q000235:genetics; D012189:Retrospective Studies; D017421:Sequence Analysis
keywords: Empowerment; Genetic counseling; Parental perspectives; Whole exome sequencing