Duplication of DNA on chromosome 7 increases risk of autism

Roughly one in five children who has an extra piece of chromosome 7 also meets the criteria for an autism diagnosis, according to a new study¹.

The study is the first rigorous look at autism features in children with a duplication of chromosomal region 7q11.23. The resulting syndrome, dubbed Dup7, can lead to intellectual disability, language problems and social anxiety. A deletion in the same region leads to Williams syndrome, a condition characterized by intellectual disability and extreme friendliness.

The researchers found that 12 of 63 children with Dup7 meet the criteria for autism, as measured by a combination of ‘gold-standard’ clinical assays and expert assessments. The results were published 6 January in the Journal of Autism and Developmental Disorders. The team has found a similar rate for children with Williams syndrome, according to unpublished data.

“Because we’re seeing similar levels of risk with the Williams kids, that suggests that there’s something going on with this region in general that is conferring risk,” says lead researcher Bonita Klein-Tasman, professor of psychology at the University of Wisconsin-Milwaukee.

Faulty recollection:

The researchers evaluated 26 girls and 37 boys with Dup7, aged 4 to 17 years, using various clinical measures. They recruited the children through doctors, parental referral and a family support organization for people with the syndrome. They then administered diagnostic tests for autism and anxiety, and questionnaires designed to rate intellectual ability.

Of the 63 children, 25 met the cutoff for autism using the Autism Diagnostic Interview-Revised (ADI-R), a clinical assessment based on an interview with parents; and 16 of the 63 met the criteria based on the Autism Diagnostic Observation Schedule (ADOS), which is an in-person assessment by a trained professional.

Licensed clinical psychologists reviewed the results of both tests, along with each child’s medical history. Based on their own analysis, they ruled out an autism diagnosis for 16 children who met the cutoff for autism on the ADI-R and 4 who did so on the ADOS.

The ADOS and ADI-R may falsely flag some children with Dup7 as having autism because their social anxiety resembles the problems these tests pick up, says Klein-Tasman. For example, a child may not ask the examiner for blocks during a task in which he is asked to build a tower, simply because he is shy.

The autism rate from this study is lower than the 30 percent seen in a 2015 report. That study evaluated children using a parent-report questionnaire called the Social Communication Questionnaire (SCQ), which is a screening tool, not a diagnostic test.

Like the ADI-R, this questionnaire also depends on parents’ accurate recall of events, and so may not accurately capture the child’s features, Klein-Tasman says.

Cutoff concern:

The researchers’ use of clinical judgement in addition to the ADOS and the ADI-R is one of the highlights of the study, says Vanessa Bal, assistant professor of psychiatry at the University of California, San Francisco.

Emotional and behavior problems, language and intellectual functioning can all affect the results of diagnostic tests, Bal notes. “We can do the best we can, but it’s really dangerous when we have researchers who are trying to say this proportion of individuals with X syndrome has autism because they meet cutoffs.”

Of the 12 children ultimately diagnosed with autism, only 2 are girls. This gender ratio is similar to the roughly 4-to-1 ratio seen for autism more generally.

The researchers also found lower rates of autism among children with Dup7 and limited speech than in those who spoke in longer sentences. This result hints that autism is more apparent in children with Dup7 who can engage in complex social interactions than in those who cannot.

As a result, children with Dup7 may typically receive autism diagnoses late, Klein-Tasman says. She plans to follow a group of children over time to confirm this theory.