Abstract
Rare genetic diseases are found in 1 in 10 individuals in the United States, and there are ∼7000 diseases found to date (Genetic Rare Disease Information Center, n.d.; U.S. Government Accountability Office, 2021). People with these diseases are often undiagnosed or misdiagnosed, and they undertake a long journey to find the cause of their symptoms (U.S. Government Accountability Office, 2021). During the journey, families must leap hurdles such as frustration from waiting for accurate results and unimaginable costs to afford genetic tests. In this study, we explore hurdles that make the diagnostic journey expensive in terms of time, financial cost, and emotions. To reduce and avoid catastrophic expenses during their journey, the families benefit from considering clinical whole genome sequencing (WGS) test, which screens the entire human genome (Miller, 2021; U.S. Government Accountability Office, 2021).
Diagnosing genetic disease is time-consuming due to diagnostic delays. Although there is a lag between recognizing the first symptoms and the first visit to the clinic, the journey is prolonged because of frequent misdiagnoses. For example, 83% of children who were ultimately diagnosed as acute disseminated encephalomyelitis were misdiagnosed at their first visit (Takahashi et al., 2021). The trend is similar in other genetic diseases: individuals with mitochondrial diseases had to visit 8.19 clinicians on average until they were accurately diagnosed (Grier et al., 2018). During the process, individuals undergo unnecessary treatments and surgeries to treat the misdiagnosed disease, and the overall journey can last from 15 months to 28 years, depending on the disease in question (U.S. Government Accountability Office, 2021).
Such delays in the journey challenge the individuals' experience of genetic diseases since timely diagnosis is critical in accessing relevant treatments to prevent comorbidities and reduce symptoms (U.S. Government Accountability Office, 2021). In response to the tedious diagnostic journey, WGS suggests a hopeful alternative by dramatically reducing the wait time. By screening the entire human genome, WGS yields results in 2.5-3 days after testing (Farnaes et al., 2018; Rossen et al., 2018). It identifies the erroneous gene with high sensitivity and even discovers new genetic diseases (Clark et al., 2018; Scocchia et al., 2019; U.S. Government Accountability Office, 2021). The molecular assessment done by the Illumina iHope program testifies to the benefits of WGS in that that it has offered clinicians for 48.8% of participants an opportunity to create a better course of clinical treatments based on the genome results (Scocchia et al., 2019).
The diagnostic journey is fraught with challenges because of the nature of the genetic diseases that lead to high costs. Mutations in genes can manifest as a wide variety of symptoms, even among individuals with the same disease. This complicates the diagnosis process, and the clinicians conduct multiple tests, ultimately putting a high financial burden on the health care system and the families. Individuals with genetic diseases undergo many diagnostic tests, such as chromosomal microarray assays, single-gene or gene-panel sequencing, and other biochemical and traditional test procedures (Lavelle et al., 2022). Although these tests are (often) at a lower cost than WGS, they must be conducted multiple times because they inspect targeted genes instead of the entire genome. Researchers estimate that a 10-year diagnostic odyssey through the standard of care methods will cost about $6566 (Lavelle et al., 2022).
Since the Human Genome Project, the rapid development of sequencing technologies reduced the cost of WGS from $500 million to $1 billion in 2003 to $20-$25 million in 2006 (Nurchis et al., 2022). Now, we are in the “$1000 genome” or less era, and the cost for WGS is projected to continue to decrease. This will make the test available for a wider population to screen for genetic diseases (Colby, 2022). WGS allows the entire human genome to be read to catch potential genetic diseases in genes that were not of interest (Colby, 2022). Such a thorough sequencing method will contribute to net health care savings by avoiding spending on unnecessary tests and reducing potential inpatient costs from diagnostic journeys by $700,000-$2 million (Farnaes et al., 2018). The reduced cost will allow families that had to choose the least-cost options, which turned into slow diagnostic journeys, to choose WGS (Miller, 2021).
Families that undertake diagnostic journeys find the process emotionally costly (U.S. Government Accountability Office, 2021). Visiting multiple clinics and looking for specialists, dealing with conflicting diagnosis, waiting for results, finding out that their disease was misdiagnosed, and realizing their treatments or surgical procedures were unnecessary, frustrating and disappointing them (Grier et al., 2018; Miller, 2021; U.S. Government Accountability Office, 2021). As parents watch their children's symptoms become more severe, they feel disempowered and helpless (Miller, 2021). Not knowing the cause of the disease to begin proper treatments and second-guessing their choices and lifestyles exasperate them (Miller, 2021).
With the single-time test of WGS, the families' emotional burden is greatly reduced because they can trust in the accurate result without traveling long distances to make multiple visits to clinicians (U.S. Government Accountability Office, 2021). Turning to WGS as the first-tier test will lighten the emotional stress that can arise from comorbidities that develop from delayed diagnoses and from high medical expenditures on unnecessary procedures to diagnose the disease (Rajan et al., 2022). As the cost for WGS is decreasing, families can receive an accurate diagnosis in a short time at an affordable cost, which will help families to avoid emotional stress in a journey that is already difficult (Grier et al., 2018; Chinnery, 2021; Nurchis et al., 2022).
Improving technologies for WGS is promising for families that struggle in their journey to diagnosis. The fast turnaround time for results and the decreasing cost make WGS widely available for families that are looking for an accurate diagnosis to begin timely treatments and for those who want to screen for genetic diseases in their families even before the symptoms develop. Existing testimonies from families and research point to WGS as a cost-effective method (Farnaes et al., 2018; Grier et al., 2018; Chinnery, 2021; Miller, 2021; U.S. Government Accountability Office, 2021; Nurchis et al., 2022; Rajan et al., 2022).
By reducing the time, money, and emotions spent to diagnose genetic diseases, WGS will assist families in finding relevant and timely treatments to find a place of normalcy in their lives. Genetic Alliance is active in our iHope Genetic Health program offering clinical WGS to undiagnosed around the world (ihopegeneticalliance.org). We also provide instant access to a rich compendium of information about the 7000 rare diseases and a couple of thousand common ones at Disease InfoSearch (www.diseaseinfosearch.org).