Developmental implications of genetic testing for physical indications

Abstract

In children undergoing genetic testing for physical health concerns, we examined how often the results also revealed information about their risk for neurodevelopmental disorders. The study sample consisted of 3056 genetic tests (1686 chromosomal microarrays--CMAs, and 1378 next-generation sequencing--NGS panels) ordered at a tertiary pediatric hospital because of a physical/congenital health problem. Tests ordered to investigate developmental concerns were excluded. Pathogenic, or likely pathogenic variants were manually reviewed for diagnostic likelihood, and for evidence of an association with a neurodevelopmental disorder (e.g., autism or intellectual disability). A total of 169 CMAs (10%) and 232 NGS panels (17%) had likely diagnostic results. More than half (52%) of all diagnostic results had established evidence of a neurodevelopmental disorder association. In summary, there is a high prevalence of neurodevelopmental implications from genetic tests ordered for physical/congenital indications. This broad clinical utility suggests a growing need for genetics-first developmental care pathways.

Fig. 1. Bar totals show diagnostic yield of individual tests; bars are subdivided by colour to show the proportions with a neurodevelopmental disorder (NDD) association among those with positive results (see Box 1 for criteria).

Full data on counts and panels are available in supplemental materials. Figure created with R and with BioRender.com. Abbreviations: Microarray: chromosomal microarray analysis; NDD: neurodevelopmental disorder; NGS: next generation sequencing panel; HHT: hereditary hemorrhagic telangiectasia; Renal panels: focal segmental glomerulosclerosis/ atypical hemolytic uremic syndrome / membranoproliferative glomerulonephritis.