Meng L, et al. - The purpose of this study was to determine the diagnostic yield and use of clinical exome sequencing in critically ill infants. It was discovered that the exome sequencing served as a powerful tool for the diagnostic evaluation of critically ill infants with suspected monogenic disorders in the neonatal and pediatric intensive care units. Its utility exerted a significant impact on the clinical decision-making.

Methods

• 278 unrelated infants underwent clinical exome sequencing, within the first 100 days of life.
• It was carried out at the Texas Children’s Hospital in Houston, Texas, during a 5-year period between December 2011 and January 2017.
• Exome sequencing types comprised of proband exome, trio exome, and critical trio exome, a rapid genomic assay for seriously ill infants.
• The main measure included indications for testing, diagnostic yield of clinical exome sequencing, turnaround time, molecular findings, patient age at diagnosis, and effect on medical management among a group of critically ill infants with suspected genetic disorders.

Results

• The mean (SEM) age of the enrollees appeared to be 28.5 (1.7) days; of these, the mean (SEM) age was 29.0 (2.2) days for infants undergoing proband exome sequencing, 31.5 (3.9) days for trio exome, and 22.7 (3.9) days for critical trio exome.
• Clinical indications for exome sequencing consisted of a range of medical concerns.
• A molecular diagnosis was attained in 102 infants (36.7%) by clinical exome sequencing, with considerably low yield for cardiovascular abnormalities.
• The diagnosis exerted an impact on the medical management for 53 infants (52.0%).
• It exhibited a significant effect on informed redirection of care, initiation of new subspecialist care, medication/dietary modifications, and advancing the life-saving procedures in few patients.
• A molecular diagnosis was found in 32 of 63 infants (50.8%) at a mean (SEM) of 33.1 (5.6) days of life with a mean (SEM) turnaround time of 13.0 (0.4) days, via critical trio exome sequencing.
• Clinical care varied due to the diagnosis in 23 of 32 patients (71.9%).
• The diagnostic yield, patient age at diagnosis, and medical effect in the group that underwent critical trio exome sequencing varied prominently than the group who underwent regular exome testing.
• The genetic disorders were molecularly diagnosed in 39 (48.1%) by exome sequencing, with implications for recurrence risk counseling, for deceased infants (n = 81).