A Review of the Genomic Analysis of Children Presenting with Developmental Delay/Intellectual Disability and Associated Dysmorphic Features

This review describes the clinical criteria of developmental delay (DD)/intellectual disability (ID) as well as the various techniques that are currently implemented to diagnose neurodevelopmental disorders that typically present with associated dysmorphic features such as Angelman syndrome, Prader-Willi syndrome, and DiGeorge syndrome. These analyses include various forms of chromosomal microarray (CMA), which have proven to be superior to previously implemented techniques such as G-banded karyotyping and fluorescent in situ hybridization (FISH) analysis, as well as whole exome sequencing (WES), which is implemented as a secondary examination when CMA analysis is unrevealing. The clinical significance of identified variants and how it relates to facilitating the management of specific genetic disorders such as the above mentioned is also discussed. In addition, the importance of genomic databases and bioinformatics technologies as they relate to variant classification is also considered. Essentially, the discovery of pathogenic variants allows for enhanced management of a patient’s clinical phenotype, whereas the identification of variants of uncertain significance (VUS) has proven to have an increase in the number of associated conflicts as they typically generate more ambiguity in regard to the clinical manifestations present within the child. As a result, additional procedures need to be implemented to mitigate the issues that surround their identification. The concluding remarks are in regard to both the ethical and legal considerations of genetic testing as they relate to informed consent, testing of minors, how to handle secondary findings, as well as the anticipated future direction of genomic analysis.