NYCKidSeq: Incorporating Genomics Into Clinical Care of Diverse NYC Children

NYCKidSeq is a research study using a randomized controlled trial (RCT) design to compare the
use of a novel communication tool 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. The communication tool 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 the communication tool.
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 a
communication tool, 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.

The Communication Tool 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.

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 Communication Tool

- 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 six 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 six months before
enrollment (*if testing was within 6-months their recruitment will be held until they
6-months or after)

Exclusion Criteria:

- The referred child is currently participating in a different genetic sequencing study

- The referred child has a known or likely genetic diagnosis for their neurologic,
immunologic, or cardiac disorder.