Last Updated : January 27, 2020
About one-half of those living with congenital anomalies (birth defects) do not have a specific cause or diagnosis identified. These individuals are given a label of “unexplained developmental delay.” It is common for these individuals to be subjected to multiple diagnostic tests, which may occur over many months or years. Genome-wide sequencing (GWS) involves technologies with the potential to provide definitive diagnoses to conditions otherwise undetected by clinical presentation and the examination of environmental causes alone.
GWS technologies (including both whole exome and whole genome sequencing) are used to evaluate and detect gene variants (mutations) that may be the cause of a certain condition. This is accomplished through a blood draw that is sent to a laboratory for analysis. After the sequencing, analysis, and interpretation of the test results, pathogenicity is labelled along a scale from pathogenic to benign. Pathogenicity refers to the potential capacity of a gene variant to cause unexplained developmental delays and multiple congenital anomalies. The American College of Medical Genetics has developed and standardized five descriptive reporting categories: pathogenic (disease-causing), likely pathogenic, variant of uncertain significance, likely benign, and benign.
GWS involves newer sequencing technologies (also referred to as next-generation sequencing) that can read large amounts of genetic information simultaneously. This makes the process substantially faster than more traditional sequencing methods but requires the efforts of multiple, highly specialized professionals working across various disciplines. These newer technologies also increase the number of genetic variants (mutations) identified that may be casually relevant to a person’s condition (i.e., variation of uncertain significance) but cannot be known with certainty.
Once test results and interpretations of pathogenicity are confirmed, they are returned to clinics and shared with patients and their families. Patients and families take this information and find ways of incorporating it into their lives. Understanding families’ and clinicians’ experiences with, and perspectives of, genetic testing can provide valuable insight into common issues families face along their journey. This knowledge can also provide clinicians with insight about how to approach conversations about genetic testing with patients and families.
A limited literature search was conducted of key resources, and titles and abstracts of the retrieved publications were reviewed. Full-text publications were evaluated for final article selection according to predetermined selection criteria (population, intervention, context or setting, outcomes, and study designs).
The literature search identified 436 citations. After screening the abstracts, 25 were deemed potentially relevant, and 13 studies met the criteria for inclusion in this review — seven semi-structured interviews, three interviews, two video-recorded consultations between geneticists and families, and one self-reported questionnaire and interview.