Fig. 1

NCGENES 2 study recruitment, enrollment, and clinical trajectory with trial arms and anticipated sample size. ^aAll eligible participants are new patients presenting for evaluation to pediatric genetics or pediatric neurology clinics. ^bEnrollment is completed by phone before the scheduled new patient visit. ^cPlanned enrollment is 850 parent-child dyads, for ease of distribution across groups, 800 was used here. ^dIntervention 1 (PVP) is a behavioral intervention that involves randomizing parents/guardians to receive or not receive a pre-visit educational booklet and a question prompt list for their child’s first clinic visit. Intervention 2 (ES) is a diagnostic intervention where parent-child dyads are randomized to be offered first-line exome sequencing for the child. The trial applies a full-factorial design, resulting in four arms, as illustrated in the figure: 1a PVP, exome sequencing, and usual care; 1b PVP and usual care; 2a exome sequencing and usual care; and 2b usual care (control arm). Estimates of positive, uncertain, and negative findings in the groups receiving ES are based on prior experience. ^eParents complete two post-return of result (ROR) surveys: (1) 2-week post-ROR (approximately 6 months after the clinic visit) and (2) 6-month post-ROR (approximately 12 months after the clinic visit). ^fClinicians complete survey measures at two timepoints: (1) post-visit survey after the clinical interaction with the child and parent and (2) approximately 6 months after the clinical visits when clinical diagnostic and ES results (if relevant) have been returned