Unraveling non-participation in genomic research: A complex interplay of barriers, facilitators, and sociocultural factors.

Undiagnosed disorders are often not amenable to the traditional diagnostic approaches and the lack of a diagnosis leads to repeated clinical consultations and laboratory testing, causing substantial personal and familial emotional and financial stress.  For parents of children with undiagnosed diseases, the extensive search for a diagnosis and inherent uncertainty surrounding their child’s health can result in stress, frustration and worries about worsening of symptoms and delays in treatment or inappropriate treatment.  As genetic testing becomes more advanced so do the expectations, associated uncertainty, and if diagnosed, an increased the frequency of a diagnosis of an ultra-rare disorder.  Thus, it is important to describe the complex emotional experience and the relationship to health care engagement and to follow this process in real time with parents as they are experiencing the diagnostic process in order to better understand their needs and to develop strategies to improve outcomes.  Challenges posed by WES for clinicians are largely by virtue of variation in the clinical relevance of results. For instance, many cases require clinical follow-up of variants of uncertain significance and secondary/incidental findings, and it has become necessary communicate effectively with patients/families at multiple stages to both educate and address expectations (pre-test counseling) and relay uncertain or less understood results (post-test counseling). Likewise, parents of children with rare disorders may be challenged to understand the process, the outcome, the certainty of the diagnosis; effectively communicate information to family members and providers; and use the new information to the benefit their of families.  Responsive to these shifting clinical needs, my research is focused on exploring how families manage genetic information with the goal of identifying genetic counseling strategies to facilitate their positive adaptation, coping, and use of information.  

Undiagnosed and rare diseases cause significant emotional and financial distress to patients who suffer from these and their families. Duke is one of seven clinical sites to be part of the NIH Undiagnosed Diseases Network (UDN). As a principal investigator for the Duke UDN site, I am involved in arranging detailed clinical evaluation for children and adults with undiagnosed diseases and in the interpretation of the genome sequencing that is performed as part of the initiative to obtain a diagnosis in these individuals. I also currently serve as the Co-Chair of the UDN steering committee. 

Chromosome 22q11.2 deletion syndrome (also known as velocardiofacial or DiGeorge syndrome: particular interests are in understanding the learning disabilities and the high risk of mental illness in these children as they get older, for which a research study is ongoing. As a clinician and researcher in this area, I run a clinic for children and adults with 22q11.2 deletion syndrome and am an investigator within the International Brain and Behavior Consortium for 22q11.2 deletion syndrome. The goal of the consortium is to conduct research to understand the genetic underpinnings of the serious mental illnesses such as schizophrenia that occur in ~25% of adolescents and adults with the condition.