A diagnosis of autism spectrum disorder specifies that the patient meets behavioral criteria that define and describe the disorder, but doesn’t specify why. Genetic testing can help identify the molecular cause in 20-25% of children with autism spectrum disorder.
A molecular diagnosis makes it possible to identify comorbidity risks. Specifically, the potential for other areas of the body such as the heart or kidneys to be affected. This in turn can help identify the need to screen for or evaluate these medical risks. And in a very small number of cases, such as metabolic disorders with an autism spectrum disorder clinical presentation, a molecular diagnosis may identify a possible treatment.
Essential vs Complex
Autism spectrum disorders are typically classified as essential or complex based on physical examination and medical plus family history review. Essential cases are unexplained. They present with no additional physical abnormalities, while complex cases present with dysmorphic features and/or microcephaly.
The physical features of complex cases may suggest a specific syndrome as the underlying cause of the autistic behavior. Syndromic autism spectrum disorders include Fragile X syndrome (caused by an expanded repeat of the FMR1 gene), Rett syndrome, tuberous sclerosis complex, Noonan syndrome, CHARGE syndrome and Sotos syndrome to list a few1. Thus these are the cases where a mutation in a single gene is most often determined as the cause.
CNVs, also known as copy number variants, explain other autism spectrum disorder cases. These mutations tend to be large deletions or duplications spanning more than one gene, but they can be as small in size as a single exon or less. Clinically-relevant, autism spectrum disorder associated CNVs include 2p16.3 (including NRXN1), 22q13.3 (including SHANK3), Xp22.3 (including PTCHD1) and others1.
The complexity of mutation types that can be at the root cause of an individual’s autism spectrum disorder has led to clinical flow charts that recommend array CGH, FMR1 testing, targeted gene testing and/or exome testing in differing orders. With the order depending upon an essential versus complex presentation, whether a specific syndrome is suspected and the results of previous genetic testing.
With its ability to detect small sequence changes, large and small CNVs, tandem repeat expansions (including FMR1 expansions) and mitochondrial variants within a single assay, Variantyx’s Genomic Unity™ test provides the most comprehensive genetic test available for identifying the underlying cause of an individual’s autism spectrum disorder.