Chromosomal Microarray Results and Medical Management for Children with Autism Spectrum Disorder and Other Developmental Conditions

Background:    As part of first-tier clinical testing for patients with autism spectrum disorder (ASD) and/or developmental delay (DD), we have performed whole genome, high density chromosomal microarray analysis (CMA) on 2200 individuals with either or both of these diagnoses over the last four years. A significant number of individuals with an ASD diagnosis (21.7%) or other developmental delays (30%) were shown to have clinically reportable genomic copy number variants (CNVs).

Objectives:  

1. To determine the magnitude of the impact of genetic testing results on diagnoses and medical management strategies. This was measured by the frequency at which a general diagnosis of ASD and/or DD could be further refined to a known syndrome or rare disease with genetic testing. Another metric we present is the frequency at which the known syndrome or rare disease has associated medical guidelines for more specific care.

2. To analyze the functional roles of the genes involved in our clinically reported CNVs and determine the specific molecular pathways most commonly represented by genes in these CNVs.

Methods:   We performed a retrospective analysis of de-identified data collected by Lineagen on 2200 individuals. We used physician-provided diagnoses and ICD-9 codes to determine clinical diagnoses of ASD and/or DD. Clinically reported CNVs were analyzed using public databases (OMIM, DECIPHER, PUBMED) for association with known syndromes, rare diseases, and accompanying medical management guidelines. DAVID software was used to perform bioinformatics analyses on genes within CNVs.

Results: A significant number of the CNVs were associated with known microdeletion/microduplication syndromes or other genetic disorders, with some of these having distinct medical guidelines for treatment and care. We occasionally found and reported incidental findings that would also affect medical management. Furthermore, bioinformatic analysis indicates that many of the genes contained in the CNVs are thought to be involved in the etiology of ASD, have known neural functions, and/or have functions in energy-related pathways. We summarize and present all these findings from our patient cohort.

Conclusions:   Our study indicates that CMA testing has significant benefit to physicians managing patients with these conditions.  Large scale, clinical CMA testing results can also give insight into potential pharmaceutical targets and the molecular pathways involved, in order that effective and targeted treatments for these conditions may be developed.