The Diagnostic Odyssey

The diagnostic odyssey is a common thread that connects all rare disease patients and families. Unfortunately, many individuals affected by rare disease are likely to go undiagnosed or misdiagnosed. The current standard of care through iterative genetic testing is less effective than whole-genome sequencing as a first tier test and may not end the diagnostic odyssey.

On average, the long search for a rare disease diagnosis—the “diagnostic odyssey”:
May involve multiple tests1
Includes up to eight physicians2-3
Take five to seven years2-5
Two to three misdiagnoses3,6

The Burden of Genetic Disease in the NICU

of live births are affected by Genetic Disorders and Congenital Anomalies7
of neonatal and pediatric admissions are secondary to birth defects or a genetic condition8-10
of NICU deaths are related to rare genetic diseases8,10-14
$12K – $77K additional hospital costs per patient in the NICU15

Who’s Affected by Rare Disease

of rare diseases are exclusively pediatric onset16
of rare diseases are exclusively adult onset16
of rare diseases are onset in both adult and pediatric groups16

A Promising

with WGS

Reduce the Diagnostic Odyssey: Answers in 72 Hours

Nathaly M. Sweeney, MD, MPH, MS, FAAP is a neonatologist at the University of California, San Diego (UCSD)/Jacobs Medical Center/Rady Children’s Hospital discusses the arc of rapid WGS through the story of a teenage girl with a rare cardiac disease.

  1. Shire Diagnosis Initiative. The Global Challenge of Rare Disease Diagnosis.
  2. Global Commission on Rare Disease. Global commission to end the diagnostic odyssey for children with a rare disease. Accessed January 6, 2023.
  3. Rare Disease Impact Report: Insights from patients and the medical community. Global Genes website. wp-content/uploads/2013/04/ShireReport-1.pdf. Published 2013. Accessed January 6, 2023.
  4. Global Genes. Allies in Rare Disease. Accessed January 6, 2023.
  5. Posada de la Paz, Taruscio, Groft. Rare diseases epidemiology: Update and overview. 2nd edition. Chapter 2. Springer 2017. Cham, Switzerland. Available from:
  6. Bogart K, Hemmesch A, Barnes E, et al. Healthcare access, satisfaction, and health-related quality of life among children and adults with rare diseases. Orphanet J Rare Dis. 2022;17(1):196. doi:10.1186/s13023-022-02343-4
  7. Farnaes, L., Hildreth, A., Sweeney, N.M. et al. Rapid whole-genome sequencing decreases infant morbidity and cost of hospitalization. npj Genomic Med 3, 10 (2018).
  8. Weiner J, Sharma J, Lantos J, Kilbride H. How infants die in the neonatal intensive care unit: trends from 1999 through 2008. Arch Pediatr Adolesc Med. 2011;165(7):630-634.
  9. Gjorgioski, S., Halliday, J., Riley, M. et al. Genetics and pediatric hospital admissions, 1985 to 2017. Genet Med 22, 1777–1785 (2020).
  10. Gunne, E., McGarvey, C., Hamilton, K. et al. A retrospective review of the contribution of rare diseases to paediatric mortality in Ireland. Orphanet J Rare Dis 15, 311 (2020).
  11. Murphy SL, Xu J, Kochanek KD, Arias E. Mortality in the United States, 2017. NCHS Data Brief. 2018(328):1-8.
  12. Arth AC, Tinker SC, Simeone RM, Ailes EC, Cragan JD, Grosse SD. Inpatient Hospitalization Costs Associated with Birth Defects Among Persons of All Ages – United States, 2013. MMWR Morb Mortal Wkly Rep. 2017;66(2):41-46.
  13. Berry MA, Shah PS, Brouillette RT, Hellmann J. Predictors of mortality and length of stay for neonates admitted to children’s hospital neonatal intensive care units. J Perinatol. 2008;28(4):297-302.
  14. Owen MJ, Wright MS, Batalov S, et al. Reclassification of the etiology of infant mortality with whole-genome sequencing. Jama Netw Open.
  15. Gonzaludo N, Belmont JW, Gainullin VG, Taft RJ. Estimating the burden and economic impact of pediatric genetic disease. Gen Med. 2018
  16. Nguengang Wakap, S., Lambert, D.M., Olry, A. et al. Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database. Eur J Hum Genet 28, 165–173 (2020).