PP05.5 – 3064: The role of exome sequencing in daily pediatric neurology practice

Abstract

Objective Pediatric neurologists aim to provide a swift and precise diagnosis and an appropriate treatment and/or supportive care procedure for children with more than a 1000 disorders of the brain, spinal cord, nerves and/or muscles. Finding a diagnosis however in many cases is not easy, not fast, not cheap and often involves burdensome procedures. Could we lower the burden and rise the diagnostic yield bij using whole exome sequencing? Methods We selected 50 patients entering the pediatric neurology department of our hospital with complicated but nonspecific clinical features with a presumed genetic origin of their disease (like developmental delay, neurodegenerative diseases, brain malformation, movement disorder, neuromuscular disease, severe epilepsy). They received standard pediatric neurology care and investigations like MRI, genomic microarray, a gene specific Sanger sequencing test, metabolic testing or muscle biopsy. Parallel to the standard care pathway, the same 50 patients were simultaneously tested using whole exome sequencing. The exome data of each patient was analysed for single nucleotide variants and insertion/deletion events, and copy number variation (CNVs) >200 kb in size. We compared both groups for diagnostic yield, health care costs and parents satisfaction. Results 50 patients (28 females, 22 males, age range 4 months–16 years) entered the study. Three patients (6%) received a conclusive genetic diagnosis in the standard care arm. In total, 28 de novo SNVs were identified, including 2 insertion/deletion events and 26 point mutations using whole exome sequencing. 10 of them were known disease causing SNVs, the other 18 where highly suspected to be pathogenic. The average costs per patient were €12,241 in the standard care, the costs of WES are currently €3,600. Conclusion Whole exome sequencing has al higher yield and lower costs to provide a diagnosis in child presumed to have a genetic origin of their disease Pediatric neurologists aim to provide a swift and precise diagnosis and an appropriate treatment and/or supportive care procedure for children with more than a 1000 disorders of the brain, spinal cord, nerves and/or muscles. Finding a diagnosis however in many cases is not easy, not fast, not cheap and often involves burdensome procedures. Could we lower the burden and rise the diagnostic yield bij using whole exome sequencing? We selected 50 patients entering the pediatric neurology department of our hospital with complicated but nonspecific clinical features with a presumed genetic origin of their disease (like developmental delay, neurodegenerative diseases, brain malformation, movement disorder, neuromuscular disease, severe epilepsy). They received standard pediatric neurology care and investigations like MRI, genomic microarray, a gene specific Sanger sequencing test, metabolic testing or muscle biopsy. Parallel to the standard care pathway, the same 50 patients were simultaneously tested using whole exome sequencing. The exome data of each patient was analysed for single nucleotide variants and insertion/deletion events, and copy number variation (CNVs) >200 kb in size. We compared both groups for diagnostic yield, health care costs and parents satisfaction. 50 patients (28 females, 22 males, age range 4 months–16 years) entered the study. Three patients (6%) received a conclusive genetic diagnosis in the standard care arm. In total, 28 de novo SNVs were identified, including 2 insertion/deletion events and 26 point mutations using whole exome sequencing. 10 of them were known disease causing SNVs, the other 18 where highly suspected to be pathogenic. The average costs per patient were €12,241 in the standard care, the costs of WES are currently €3,600. Whole exome sequencing has al higher yield and lower costs to provide a diagnosis in child presumed to have a genetic origin of their disease