Chromosomal Microarray Analysis of Consecutive Individuals with Autism Spectrum Disorders Using an Ultra-High Resolution Chromosomal Microarray Optimized for Neurodevelopmental Disorders.

Karen Ho,E Wassman,Rena Vanzo,Hope Twede,Megan Martin,Aparna Prasad,Charles Hensel,Adrianne Baxter,Merlin Butler

doi:10.3390/ijms17122070

Abstract

Copy number variants (CNVs) detected by chromosomal microarray analysis (CMA) significantly contribute to understanding the etiology of autism spectrum disorder (ASD) and other related conditions. In recognition of the value of CMA testing and its impact on medical management, CMA is in medical guidelines as a first-tier test in the evaluation of children with these disorders. As CMA becomes adopted into routine care for these patients, it becomes increasingly important to report these clinical findings. This study summarizes the results of over 4 years of CMA testing by a CLIA-certified clinical testing laboratory. Using a 2.8 million probe microarray optimized for the detection of CNVs associated with neurodevelopmental disorders, we report an overall CNV detection rate of 28.1% in 10,351 consecutive patients, which rises to nearly 33% in cases without ASD, with only developmental delay/intellectual disability (DD/ID) and/or multiple congenital anomalies (MCA). The overall detection rate for individuals with ASD is also significant at 24.4%. The detection rate and pathogenic yield of CMA vary significantly with the indications for testing, age, and gender, as well as the specialty of the ordering doctor. We note discrete differences in the most common recurrent CNVs found in individuals with or without a diagnosis of ASD.

Highlights

Neurodevelopmental disabilities, including developmental delay (DD), intellectual disability (ID), and autism spectrum disorder (ASD) affect up to 15% of children [1]
Along with previously recognized indications of DD, ID and multiple congenital anomalies (MCA), children and adults presenting with ASD should be offered chromosomal microarray analysis (CMA) as a first tier genetic evaluation based on the clinical guidelines from multiple professional societies [2,3,4,5,6,7,8,9,10]
* “Non-ASD” represents that portion of the cohort with no testing indication of ASD; † “Any ASD” refers to the portion of the cohort that has ASD as a sole testing indication, or in combination with any other testing indications, it represents both “ASD only” and “ASD+” cohorts combined; ‡ “ASD+” refers to the portion of the cohort with an indication of ASD as well as another testing indication, such as MCA, seizures, DD, and/or ID; § “ASD only” refers to the portion of the cohort with ASD as the only testing indication

Summary

Introduction

Neurodevelopmental disabilities, including developmental delay (DD), intellectual disability (ID), and autism spectrum disorder (ASD) affect up to 15% of children [1]. Genetic testing to pinpoint the underlying cause of ASD is critical to an individual’s clinical management. Chromosomal microarray analysis (CMA) has demonstrated the highest diagnostic yield for individuals with ASD as compared to other genetic tests. Along with previously recognized indications of DD, ID and multiple congenital anomalies (MCA), children and adults presenting with ASD should be offered CMA as a first tier genetic evaluation based on the clinical guidelines from multiple professional societies [2,3,4,5,6,7,8,9,10]

Methods

Results

Discussion

Conclusion