The influence of social determinants of health on the genetic diagnostic odyssey: who remains undiagnosed, why, and to what effect?

Abstract

Although Mendelian genetic disorders are individually rare, they are collectively more common and contribute disproportionately to pediatric morbidity and mortality. Remarkable advances in the past decade have led to identification of the precise genetic variants responsible for many of these conditions. Confirming the molecular diagnosis through genetic testing allows for individualized treatment plans in addition to ending the diagnostic odyssey, which not only halts further unnecessary testing but may also result in immense psychological benefit, leading to improved quality of life. However, ensuring equitable application of these advances in genomic technology has been challenging. Though prior studies have revealed disparities in testing for genetic predisposition to cancer in adults, little is known about the prevalence and nature of disparities in diagnostic testing in the pediatric rare disease population. While it seems logical that those with impaired access to healthcare would be less likely to receive the genetic testing needed to end their odyssey, few studies have addressed this question directly and the potential impact on health outcomes. This review synthesizes the available evidence regarding disparities in pediatric genetic diagnosis, defining the need for further, prospective studies with the ultimate goal of delivering precision medicine to all who stand to benefit. IMPACT: Social determinants of health are known to contribute to inequality in outcomes, though the impact on pediatric rare disease patients is not fully understood. Diagnostic genetic testing is a powerful tool, though it may not be available to all in need. This article represents the first effort, to our knowledge, to evaluate the existing literature regarding disparities in genetic testing for pediatric rare disease diagnosis and identify gaps in care.

Figure.

Illustrating the process of identifying a genetic diagnosis for rare disease patients and the possible interference of social determinants of health.