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. 2020 Jun;22(6):986-1004.
doi: 10.1038/s41436-020-0771-z. Epub 2020 Mar 23.

Systematic evidence-based review: outcomes from exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability

Jennifer Malinowski #  1 , David T Miller #  2 , Laurie Demmer  3 , Jennifer Gannon  4   5 , Elaine Maria Pereira  6 , Molly C Schroeder  7 , Maren T Scheuner  8   9 , Anne Chun-Hui Tsai  10 , Scott E Hickey #  11 , Jun Shen #  12 ; ACMG Professional Practice and Guidelines Committee
Affiliations

Systematic evidence-based review: outcomes from exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability

Jennifer Malinowski et al. Genet Med. 2020 Jun.

Abstract

Purpose: Exome and genome sequencing (ES/GS) are performed frequently in patients with congenital anomalies, developmental delay, or intellectual disability (CA/DD/ID), but the impact of results from ES/GS on clinical management and patient outcomes is not well characterized. A systematic evidence review (SER) can support future evidence-based guideline development for use of ES/GS in this patient population.

Methods: We undertook an SER to identify primary literature from January 2007 to March 2019 describing health, clinical, reproductive, and psychosocial outcomes resulting from ES/GS in patients with CA/DD/ID. A narrative synthesis of results was performed.

Results: We retrieved 2654 publications for full-text review from 7178 articles. Only 167 articles met our inclusion criteria, and these were primarily case reports or small case series of fewer than 20 patients. The most frequently reported outcomes from ES/GS were changes to clinical management or reproductive decision-making. Two studies reported on the reduction of mortality or morbidity or impact on quality of life following ES/GS.

Conclusion: There is evidence that ES/GS for patients with CA/DD/ID informs clinical and reproductive decision-making, which could lead to improved outcomes for patients and their family members. Further research is needed to generate evidence regarding health outcomes to inform robust guidelines regarding ES/GS in the care of patients with CA/DD/ID.

Keywords: clinical genetics; congenital anomalies; exome sequencing; intellectual disability; systematic evidence review.

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Conflict of interest statement

S.E.H. received research support from Alexion Pharmaceuticals to serve as a site investigator for a prospective registry for hypophosphatasia. D.T.M. received honoraria from Prevention Genetics and Takeda Pharmaceuticals. M.C.S. receives salary (no equity) as a lab director at Washington University School of Medicine, received salary (no equity) as a lab director at HudsonAlpha Institute of Biotechnology (performs clinical whole genome sequencing), and received consulting fees from PierianDx. J.S. received salary from the Partners Healthcare Laboratory for Molecular Medicine and from the Brigham and Women’s Hospital Cytogenomics Laboratory. The other authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1. Analytic framework for evaluating outcomes of exome/genome sequencing (ES/GS) for patients with congenital anomalies (CA) or developmental delay/intellectual disability (DD/ID).
KQ key question.
Fig. 2
Fig. 2. PRISMA flowchart.
CA congenital anomalies, DD/ID developmental delay/intellectual disability.
See this image and copyright information in PMC

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