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Incidental Findings in Rapid Exome and Genome Testing in Pediatric ICU: Clinical and Psychological Implications 

Clinical Genetics and Therapeutics
  • Primary Categories:
    • Clinical Genetics
  • Secondary Categories:
    • Clinical Genetics
Introduction
Rapid exome and genome sequencing in critically ill pediatric patients have been shown in multiple medical literature papers to improve diagnostic yield, provide prognostic insights, have management implications, on top of their cost-effective value. ACMG has published its most recent policy statement for incidental findings reporting in 2023. Primary team as well as parents of critically ill pediatric patients with suspected genetic syndrome often focus on reaching a diagnosis while the possibility of having an actionable incidental finding is overlooked. Incidental findings reported in rapid exome and genome sequencing represent an array of challenges including potential patient’s complications, management changes , and parental healthcare implications. Additionally, they can create a psychological challenge for the family. 

 

 

Case Presentation
Our patient is a male presented prenatally with abdominal cystic structure identified at 21 weeks gestation. Fetal ultrasound showed the bladder to extend up to the diaphragm and has compressed the thoracic cavity in addition to hydronephrosis and oligohydramnios. No other structural abnormalities seen. The mother’s NIPT for trisomy 13,18, 21, and sex aneuploidy was low risk. Prenatal karyotype resulted 46, XY and SNP array resulted normal male. He underwent fetal vesicoamniotic shunting at 22 weeks of gestation. He was born at 28 weeks and his broth weight, length, and head circumference were appropriate for gestational age. His APGARS were 4 at 1 minute and 5 and 5 minutes. He was intubated and put on oscillator. His physical exam showed wrinkled abdomen and no dysmorphic features. His abdominal ultrasound showed bilateral pelviectasis. His echocardiogram was tricuspid regurgitation with no structural abnormalities. 

Diagnostic Workup
His initial genetic testing for CHRM3 gene (Prune Belly Syndrome) was negative. Subsequently, his 

trio rapid exome sequencing was diagnostic and identified a de novo pathogenic variant in ACTG2 gene (c.532 C>A p.R178S), confirming his diagnosis of autosomal dominant Megacystis-Microcolon- Intestinal Hypoperistalsis Syndrome (MMIHS). His rapid exome sequencing also identified an incidental finding in DSG2 gene (c.1826dupG p.L610PfsX50), confirming his diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC). Of note, both parents initially declined incidental findings testing for themselves. Both parents were experiencing a psychological dilemma about testing for incidental finding. After extensive counseling and support provided by social worker and psychology, they agreed to test for the incidental finding and the father was tested positive. 

 

Treatment and Management
He was asymptomatic. The father was evaluated by cardiology and arrhythmia was detected and he was started on pharmacological treatment for ARVC with beta blockers. Additionally, our pediatric patient was found to have ARVC at age 4 years and was started on beta blocker.

 

Conclusion
     Incidental findings in rapid exome and genome sequencing for critically ill pediatric patients represent extra layers of challenges both medically and psychologically. It requires a team effort to work with families to overcome those challenges. Our patient adds to the available medical literature about the value of rapid exome and genome sequencing in critically ill pediatric patients and the importance of counseling on incidental findings. It is very crucial not to overlook incidental findings and their medical as well as psychological impact. Timely diagnosis and intervention of incidental findings is life-saving as seen in our patient and his father. 

 

 

Agenda

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