Kids With Genetic Disorder Often Misdiagnosed With Autism

Deborah Brauser

September 25, 2013

Children with a genetic disorder known as 22q11.2 deletion syndrome (22q) who are also frequently thought to have autism spectrum disorder (ASD) are often misdiagnosed, new research suggests.

Social impairment associated with the developmental delays from 22q may be mimicking the features of ASD, which can then lead to an ASD misdiagnosis, according to investigators.

Results from the study showed that of 29 children with 22q, none met the strict diagnostic criteria for autism ― which include elevated scores on both the gold standard Autism Diagnostic Observation Schedule (ADOS) and the Social Communication Questionnaire (SCQ).

"Although we saw a lot of social impairments in these kids, it fit our assessment that there was something a little different about them," senior author Tony J. Simon, PhD, professor of psychiatry and behavioral sciences at the University of California–Davis MIND Institute and director of the Institute's 22q program, told Medscape Medical News.

"The point of our research was to try and explain what basic cognitive and behavioral issues are driving this population so that we can then target these issues more directly to reduce difficulties," he said.

If this explanation can be developed, it may point to "specific targets for intervention that are appropriate and effective for children with [22q] where interventions for ASD might well not be," the investigators write.

The study was published online September 17 in the Journal of Autism and Developmental Disorders.

High Prevalence of ASD?

Other names for 22q include velocardiofacial syndrome and DiGeorge syndrome. This disorder, which affects roughly 1 in 2000 individuals, has been associated with congenital heart disease, immune difficulties, hypocalcemia, learning disabilities, and psychiatric problems such as anxiety and attention-deficit/hyperactivity disorder (ADHD).

The researchers note that although previous research has reported autism prevalence rates of between 20% and 50% in children with 22q, these data are mainly based on parent-reported measures.

For the current study, the investigators sought to use both the ADOS, which is a standardized observation measure, and the SCQ, which is a parent-completed questionnaire, to better assess the prevalence of ASD.

The investigators report that in the cases of idiopathic ASD, social functioning impairments tend to be pervasive in multiple environments. However, the social impairments in those with 22q tend to be more situation or context specific.

They hypothesized that these impairments by the kids with 22q "might better be explained by a combination of intellectual delays and affective dysregulation rather than autism spectrum disorders per se."

In fact, they add that these children often show considerable social drive, a sense of humor, and empathy ― especially toward younger peers.

For the current analysis, the researchers examined a subset of 29 children (55% boys) who were participating in a larger study of neurocognitive function. All were between the ages of 7 and 14 years and had molecularly confirmed 22q.

Both the ADOS and the SCQ were used to calculate a possible ASD diagnosis in the participants.

In addition, the Behavioral Assessment System for Children, 2nd Edition, Parent Rating Scales (BASC-2 PRS) was administered in a parallel study to parents of these participants, as well as to those of others who participated in the overall larger study but who did not have ADOS scores. This yielded BASC-2 PRS scores for 100 children.

Toward More Positive Outcomes

Results of the study showed that none of the participants had elevated ADOS and SCQ scores. Although 5 of the children scored in the elevated range on the ADOS, only 1 of these had scores higher than the autism cutoff point.

All of the 29 children showed strengths on the ADOS in social interaction and weaknesses in insight and imagination. The 5 who had elevated overall ADOS scores showed relative weaknesses in communication.

Two of the children who did not score high on the ADOS had SCQ scores above the cutoff of 15, which is used to indicate concern for ASD symptoms.

When examining results from the second study, 4 of the 5 children who had elevated ADOS scores also had elevated anxiety and/or somatization scores on the BASC-2 PRS.

Interestingly, 44 of the 100 children with BASC-2 PRS scores screened positive for ASD, on the basis of elevated scores on the Developmental Social Disorders scale.

"It seems that the difference in diagnostic methodology is the primary reason for the discrepancy between the percentage of children meeting criteria for an ASD diagnosis in our study and the prevalence of ASD in the [22q] literature," write the investigators.

They add that comorbid conditions, such as anxiety, may also be contributors to the falsely elevated ASD prevalence reports.

"Information from multiple sources should be included in the evaluation of ASD," they write. "This would directly impact treatment recommendations and patient care procedures."

Lead author Kathleen Angkustsiri, MD, assistant professor of developmental-behavioral pediatrics at the MIND Institute, said in a release that there are a variety of different avenues that might be better pursued instead of using treatments designed specifically to help with ASD symptoms, including adaptive behavioral analysis.

"There are readily available, evidence-based treatments that may be more appropriate to help maximize these children's potential," she said, adding that further study should also focus on ways to improve the communication skills of this population, decrease their anxiety, and help them to remain focused and on task.

Dr. Tony Simon

"This is also a population that is at a very high risk for schizophrenia later in life," added Dr. Simon.

"The whole mission here really is to generate explanations of the reasons for the symptoms that we see that are consistent with different kinds of psychopathology diagnoses and then try to target those specific things for treatment so the outcomes will be more positive."

Accurate Diagnosis Is Key

"Overall, I think this is an interesting study and something that has really needed to be done ― not only for this syndrome but for many other disorders as well," Sarah H. Elsea, PhD, associate professor in the Department of Molecular and Human Genetics at Baylor College of Medicine in Houston, Texas, told Medscape Medical News.

Dr. Sarah Elsea

"The data showing that autism may not be prevalent in this population, and in fact there may be other mechanisms that may be leading clinicians to consider autism, is very important for potential therapy."

Dr. Elsea, who was not involved with this research, noted that the study also shows that clinicians should look a little more carefully at those with 22q and with other similar types of chromosomal abnormalities.

"It's important to realize that each disorder may be unique and may not fall into a broader class of [ASD]. Having a proper diagnosis is really key for everyone so they can get the proper therapies," she said.

"At some levels, autism is an easier diagnosis and one that people in the community understand. But a diagnosis that is a little more specific may be much more beneficial to the child," Dr. Elsea concluded.

The study was funded by grants from the National Institutes of Health, the National Center for Advancing Translational Sciences, the Children's Miracle Network, the Dempster Family Foundation, and the University Center for Excellence in Developmental Disabilities. The study authors and Dr. Elsea have disclosed no relevant financial relationships.

J Autism Dev Disord. Published online September 17, 2013. Abstract


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