CLINICAL UTILITY OF NEXT GENERATION SEQUENCING IN NEURODEVELOPMENTAL DISORDERS —EXPERIENCE FROM A TERTIARY CARE CENTRE

CLINICAL UTILITY OF NEXT GENERATION SEQUENCING IN NEURODEVELOPMENTAL DISORDERS —EXPERIENCE FROM A TERTIARY CARE CENTRE

OBJECTIVE To identify the clinical utility of Next Generation Sequencing (NGS) in Neurodevelopmental Disorders.

METHODS This is a retrospective observational analysis (June 2017 to May 2021) of children satisfying the DSM V criteria for NDDs attending the Comprehensive Care Centre for Neurodevelopmental Disorders of our Institute on whom NGS was performed. Relevant clinical and genetic details of the patients were recorded. American College of Medical Genetics (ACMGE) criteria were used to classify the genetic variants.

RESULTS The study included 75 patients with a median age of 67 months and 52% (39) were males. The predominant phenotypic presentation were global developmental delay (37%) and autism spectrum disorders (28%). As per ACMGE classification, pathogenic variants, likely pathogenic and variants of unknown significance were observed in 15, 5, and 40 patients respectively. Among the 20 pathogenic /likely pathogenic variants, 6 deletions, 6 missense, 4 nonsense variants, 3 splice site and one duplication were detected. The target genes identified were SMC1A, CAD, MECP2, CDKL5, GNAO1,OCRL, IQSEC2, SLC9A1, NUS1, TTC8, ELOVL4, GNB5, DVL3, GSDME, ALDH3A2, SCN1A, OPA1, AHI1, EP300 and SPAST. Female gender, microcephaly and dysmorphic facies were more prevalent in patients identified with pathogenic/likely pathogenic variants. The diagnostic yield for pathogenic/likely pathogenic was 27% and on including VUS, the yield increased to 80 %.

CONCLUSION The diagnostic yield from NGS among NDDs are high and should be considered during their clinical evaluation.
Keywords: NDD- NeuroDevelopmental Disorders, NGS -Next Generation Sequencing