Genomic Medicine for Ill Neonates and Infants (The GEMINI Study)

This multicenter, prospective clinical trial will examine the diagnostic yield and clinical utility of NewbornDx, a targeted genomic sequencing panel for use in the neonate, and rapid whole genomic sequencing (rWGS) testing in high-risk infants with signs/symptoms consistent with a possible genetic disorder. Infants will undergo NewbornDx and rWGS (proband) testing. The biological parent(s), when available, will undergo NewbornDx testing at the same time as the infant. For rWGS,the infant will undergo testing first. If a specific diagnosis that is consistent with the phenotype is not made with rWGS proband analysis alone, the parent(s) will undergo rWGS. The study will also evaluate the cost effectiveness of each test as well as standard of care (SOC) testing. A retrospective chart review of infants with suspected genetic disorders will be done to understand 1-year cost and health outcomes that would have been incurred in the absence of the advanced testing. The resulting data from the trial will be used in the economic evaluation comparing NewbornDx, rWGS, and SOC over a 1-year period and used as basis to simulate the lifetime cost-effectiveness of these testing strategies. A web-based clinical reference database to provide references, clinical management guidelines, opportunities for clinical trial participation, and support groups for each condition will be developed with separate interfaces for the parent/guardian(s) and medical provider. The clinical reference database will be qualitatively assessed by a survey of medical providers.

Inclusion criteria

• Documented informed consent from the parent/guardian
• Signs/symptoms consistent with a possible genetic disorder
• Admitted to a hospital participating in this study at the time of enrollment
• Less than one year corrected gestational age

Exclusion criteria

• A known genetic diagnosis (e.g. prenatal testing)
• Major congenital anomaly associated with a chromosomal anomaly detected on prenatal testing
• Presence of documented congenital infection
• Infants considered non-viable due to prematurity (< 23 0/7 weeks GA)