nyckidseq: incorporating genomics into clinical care of diverse nyc children

Conditions: Genetic Diseases, Inborn; Genetic Predisposition to Disease

Summary: the nyckidseq program will significantly advance the implementation of genomic medicine, particularly for children, young adults and their families in harlem and the bronx. the study will assess the clinical utility of genomic medicine in three broad areas of pediatric disorders, while engaging a range of providers and community advisors to overcome the well-documented barriers to inclusion of underserved and underrepresented populations in genomic research. the study will also include testing, analyzing, and implementing a novel communication tool, genomic understanding, information and awareness (guía), to facilitate the return of genomic test results. the use of guía will enhance the understanding of these genomic testing results by families, patients, and care providers at all levels of expertise, in two health systems. healthcare system leadership will be engaged to provide insights into their readiness for genomic implementation. overall, the nyckidseq program will inform the genomics and clinical communities about how to implement genomic medicine in a diverse population in a clinically useful, technologically savvy, culturally sensitive, and ethically sound manner.

nyckidseq is a research study using a randomized controlled trial (rct) design to compare the use of guía in a traditional genetic counseling return of results session to facilitate the return of genomic results compared to a traditional return of results counseling session. guía will be an enhanced, personalized electronic version focused on helping patients understand their own genomic results. the researchers will also evaluate the clinical utility of whole genome sequencing (wgs) compared to targeted gene panels (tgp) in children with suspected genetic etiology of their neurologic disorders, primary immunodeficiencies, and cardiovascular disorders with the goal of detecting the mutated gene(s) responsible for their disorder. 1100 referred children mount sinai and albert einstein college of medicine/montefiore hospital (einstein/montefiore) will be enrolled and randomized to either traditional genetic counseling (standard of care) or traditional genetic counseling plus guía. the researchers will assess parents' perceived and subjective understanding of results as well as their adherence to follow-up recommendation (primary and secondary outcomes) through the use of parental surveys at three time points. the rct will occur in the context of performing wgs and tgp for diagnostic purposes in 1,130 children. participants will have three study visits (baseline, ror1, and ror2) over a nine-month period. at the baseline visit, families will receive pre-test counseling and will complete a survey. blood will be collected from all study participants and from each biological parent (if available) to assist with interpretation of genomic results. samples will undergo wgs and tgp. approximately three months later, results will be returned and explained via one of the two study arms - traditional genetic counseling versus genetic counseling with guía, and parents will be asked to complete the ror1 survey. six months later, they will be asked to complete the ror2 survey. the length of a subject's participation will be a minimum of nine months to a maximum of 27 months, depending on the time of study entry; participation after the initial nine months will consist solely of chart and data review. over the initial 9-month period the investigators are studying the experiences and understanding of parents of children who receive sequencing to help understand how best to implement genomic medicine in a diverse population. guía will be an enhanced, personalized electronic version of a flip chart, which is the type of tool most commonly used in routine genetic counseling. in the third year of the study, the study team anticipates to have the tool integrated into epic. there are no tools yet focused on this complex information, specifically on helping patients understand their own genomic results.

Eligibility criteria:
inclusion criteria: * infants, children and young adults up to and including 21 years of age; young adults (18-21) who are cognitively intact may participate in this study, but their parent(s) or legal guardian(s) must also agree to participate * english- or spanish-speaking parent or legal guardian capable of providing informed consent, participating in surveys, and able to see guia; * currently undiagnosed, likely genetic\* cause of neurologic, immunologic, or cardiac disorders (\*as determined by disorder-specific criteria in section iiic. and phenotype checklist appendix w.) * followed by a physician in the ms or em systems; * willing and able to return for each study visit (not moving out of the area within nine months) * if targeted gene panels and/or whole exome sequencing were previously done, results must have been returned at least three months before enrollment; * if targeted gene panels and/or whole exome sequencing were previously done, results must have been negative, or identified only one variant in a potentially causative autosomal recessive gene, and * if the parents received genetic counseling about this child, themselves, or a family member, the last genetic counseling session must have been at least three months before enrollment (\*if testing was within 6-months their recruitment will be held until they 3-months or after) * if patients have undergone karyotyping alone, we do not have to wait 3 months prior to inclusion. exclusion criteria: * the referred child is currently participating in a different genetic sequencing study, that includes genetic counseling and/or return of results before the participant's ror2 visit. * the referred child has a known or likely molecular genetic diagnosis for their neurologic, immunologic, or cardiac disorder. * the referred child has had a bone-marrow transplant.

Keywords: whole genome sequencing genetic counseling hereditary childhood disease genomic medicine