Identifying a precise genetic diagnosis can improve outcomes for individuals with rare disease, though the resources required to do so may impede access and exacerbate healthcare disparities leading to inequitable care. Our objective was therefore to determine the effect of multiple sociodemographic factors on the yield of the diagnostic evaluation for genetics outpatients.
This is a retrospective cohort study from 2017 to 2019 of outpatient genetics referrals at a pediatric academic tertiary care center. Exposures included: primary language, insurance type, and neighborhood resources (via the Childhood Opportunity Index, COI). The primary outcome was identification of a genetic diagnosis within 2 years of the initial clinic visit.
COI quintile was not significantly associated with the odds of diagnosis but was significantly associated with clinic attendance, with lower neighborhood resources leading to incomplete referrals. Limited English proficiency was associated with a higher odds of diagnosis, though at an older age. Public insurance was associated with increased access to genetic testing.
Lower neighborhood resources are negatively associated with clinic attendance. Our findings further suggest delays in care and a referral bias for more severe phenotypes among families with limited English proficiency. Improved access to clinical genetics is needed to improve diagnostic equity.
The resources required to identify a genetic diagnosis may impede access and exacerbate healthcare disparities leading to inequitable care.
In an analysis of pediatric outpatient genetics referrals, we observed a significant association between neighborhood resources and clinic attendance but not diagnostic yield for those attending, and a higher diagnostic yield for families with limited English proficiency, suggesting referral bias for more severe phenotypes.
Thus, the primary barrier to finding a genetic diagnosis was initiation of care, not the ensuing diagnostic odyssey.
Further research efforts should be directed at increasing access to clinical genetics evaluations for children with rare disease.
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To protect patient privacy, the dataset generated and analyzed during the current study may be available from the corresponding author on reasonable request contingent on a data use agreement.
Gonzaludo, N., Belmont, J. W., Gainullin, V. G. & Taft, R. J. Estimating the burden and economic impact of pediatric genetic disease. Genet. Med. 21, 1781–1789 (2019).
Arth, A. C. et al. Inpatient hospitalization costs associated with birth defects among persons of all ages - United States, 2013. MMWR Morb. Mortal. Wkly Rep. 66, 41–46 (2017).
Wojcik, M. H. et al. Infant mortality: the contribution of genetic disorders. J. Perinatol. 39, 1611–1619 (2019).
Boyle, B. et al. Estimating global burden of disease due to congenital anomaly: an analysis of European data. Arch. Dis. Child. Fetal Neonatal Ed. 103, F22–F28 (2018).
Haendel, M. et al. How many rare diseases are there? Nat. Rev. Drug Discov. 19, 77–78 (2020).
Navarrete-Opazo, A. A., Singh, M., Tisdale, A., Cutillo, C. M. & Garrison, S. R. Can you hear us now? The impact of health-care utilization by rare disease patients in the United States. Genet. Med. 3, 2194–2201 (2021).
Coulter, M. E. et al. Chromosomal microarray testing influences medical management. Genet. Med. 13, 770–776 (2011).
Stark, Z. et al. Does genomic sequencing early in the diagnostic trajectory make a difference? A follow-up study of clinical outcomes and cost-effectiveness. Genet. Med. 21, 173–180 (2019).
Kim, J. et al. Patient-customized oligonucleotide therapy for a rare genetic disease. N. Engl. J. Med. 381, 1644–1652 (2019).
Jenkins, B. D. et al. The 2019 US medical genetics workforce: a focus on clinical genetics. Genet. Med. 23, 1458–1464 (2021).
Maiese, D. R. et al. Current conditions in medical genetics practice. Genet. Med. 21, 1874–1877 (2019).
Bohnhoff, J. C., Taormina, J. M., Ferrante, L., Wolfson, D. & Ray, K. N. Unscheduled referrals and unattended appointments after pediatric subspecialty referral. Pediatrics 144, e20190545 (2019).
Fraiman, Y. S. & Wojcik, M. H. The influence of social determinants of health on the genetic diagnostic odyssey: who remains undiagnosed, why, and to what effect? Pediatr. Res. 89, 295–300 (2021).
Koretzky, M. et al. Towards a more representative morphology: clinical and ethical considerations for including diverse populations in diagnostic genetic atlases. Genet. Med. 18, 1069–1074 (2016).
Carmichael, N. et al. "Is it going to hurt?": the impact of the diagnostic odyssey on children and their families. J. Genet. Couns. 24, 325–335 (2015).
Landry, L. G. & Rehm, H. L. Association of racial/ethnic categories with the ability of genetic tests to detect a cause of cardiomyopathy. JAMA Cardiol. 3, 341–345 (2018).
Suther, S. & Kiros, G. E. Barriers to the use of genetic testing: a study of racial and ethnic disparities. Genet. Med. 11, 655–662 (2009).
Bonkowsky, J. L., Wilkes, J., Bardsley, T., Urbik, V. M. & Stoddard, G. Association of diagnosis of leukodystrophy with race and ethnicity among pediatric and adolescent patients. JAMA Netw. Open 1, e185031 (2018).
Wojcik, G. L. et al. Genetic analyses of diverse populations improves discovery for complex traits. Nature 570, 514–518 (2019).
Armstrong, K., Micco, E., Carney, A., Stopfer, J. & Putt, M. Racial differences in the use of BRCA1/2 testing among women with a family history of breast or ovarian cancer. JAMA 293, 1729–1736 (2005).
Olaya, W. et al. Disparities in BRCA testing: when insurance coverage is not a barrier. Am. J. Surg. 198, 562–565 (2009).
Slavin, T. P. et al. Prospective study of cancer genetic variants: variation in rate of reclassification by ancestry. J. Natl Cancer Inst. 110, 1059–1066 (2018).
Harris, P. A. et al. Research electronic data capture (REDCap) - a metadata-driven methodology and workflow process for providing translational research informatics support. J. Biomed. Inf. 42, 377–381 (2009).
Acevedo-Garcia, D. et al. The child opportunity index: improving collaboration between community development and public health. Health Aff. 33, 1948–1957 (2014).
Clark, M. M. et al. Meta-analysis of the diagnostic and clinical utility of genome and exome sequencing and chromosomal microarray in children with suspected genetic diseases. NPJ Genom. Med. 3, 16 (2018).
Hussain, S. B., Quittner, A. L., Brown, M. & Li-Rosi, A. M. Understanding access to genomics in an ethnically diverse south Florida population: a comparison of demographics in odyssey and rapid whole genome sequencing programs. J. Genet. Couns. 29, 553–561 (2020).
Walley, N. M. et al. Characteristics of undiagnosed diseases network applicants: implications for referring providers. BMC Health Serv. Res. 18, 652 (2018).
Pasquini, T. L. S., Goff, S. L. & Whitehill, J. M. Navigating the U.S. health insurance landscape for children with rare diseases: a qualitative study of parents' experiences. Orphanet J. Rare Dis. 16, 313 (2021).
Smith, H. S. et al. Outcomes of prior authorization requests for genetic testing in outpatient pediatric genetics clinics. Genet. Med. 23, 950–955 (2021).
Monies, D. et al. The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes. Hum. Genet. 136, 921–939 (2017).
Acevedo-Garcia, D. et al. Racial and ethnic inequities in children's neighborhoods: evidence from the new Child Opportunity Index 2.0. Health Aff. 39, 1693–1701 (2020).
Manrai, A. K. et al. Genetic misdiagnoses and the potential for health disparities. N. Engl. J. Med. 375, 655–665 (2016).
Wojcik, M. H. & Fraiman, Y. S. Further considerations on the value of whole-genome sequencing in critically ill infants. JAMA Pediatr. 176, 420–421 (2022).
The authors thank the geneticists and genetic counselors that we work with who work tirelessly to provide equitable care in their clinical practice. We also thank Dr. Henry Feldman for statistical support.
M.H.W. was supported by a Boston Children’s Hospital Medical Staff Organization Faculty Innovated Research Award and the National Institute of Child Health and Human Development K23 HD102589. M.B. was supported by the Harvard Neonatal-Perinatal Medicine Summer Student Research Program. The other authors received no external funding. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
The authors declare no competing interests.
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Wojcik, M.H., Bresnahan, M., del Rosario, M.C. et al. Rare diseases, common barriers: disparities in pediatric clinical genetics outcomes. Pediatr Res (2022). https://doi.org/10.1038/s41390-022-02240-3