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Autism with genetic abnormalities presents differently, more subdued

Children with autism spectrum disorders with de novo mutations may present with subdued social communication and language skills compared with those without genetic abnormalities.

“Microarray analysis and whole exome sequencing in large data sets like the Simons Simplex Collection (SSC) have identified numerous ASD–associated genetic loci in probands and have clearly demonstrated an important role for highly penetrant de novo genetic mutations in individuals previously assumed to have idiopathic ASD and specifically selected for minimal syndromic features,” Somer L. Bishop, PhD, of University of California, San Francisco, and colleagues wrote. “These findings highlight the importance of changing methodological standards to require genetic testing prior to idiopathic classification, but they also leave open the question of whether individuals with identifiable genetic abnormalities are phenotypically distinguishable.”

To expand upon SSC findings, researchers compared phenotypic profiles of ASD probands with or without identified de novo loss of function mutations or copy number variants in high-confidence ASD–associated genes or loci. Analysis included 112 children with de novo mutations.

Study participants with de novo mutations were more likely to exhibit motor delay during early development but exhibited less impairment on some ASD core symptoms, such as parent-rated social communication abnormalities and clinician-rated certainty about ASD, later in childhood.

Children with de novo mutations exhibited relatively strong verbal and language abilities, including a smaller difference between nonverbal and verbal IQ and greater tendency to achieve language fluency.

“These results highlight the critical need to consider ASD–related symptoms and behaviors in the context of overall developmental level,” the researchers wrote. “The differences between individuals with and without de novo mutations were only revealed when sex, IQ, and age were carefully controlled in the analyses. Proper steps must be taken to account for these factors in future studies in order to advance our understanding of the range of phenotypic profiles associated with genetic findings in ASD.” – by Amanda Oldt

Disclosure: Bishop reports royalties from Western Psychological Services for the publication of the Autism Diagnostic Observation Schedule, 2nd Edition; and all royalties received related to any research in which Bishop is involved are given to a not-for-profit agency. Please see the study for a full list of relevant financial disclosures.