Revised Scales Better – But Not Enough – for Diagnosing Autism in Fragile X, Study Finds

Researchers adapted two scales commonly used to screen for autism spectrum disorder (ASD) — the social communication questionnaire (SCQ) and the social responsiveness scale (SRS-2) — with the aim of better diagnosing autism in people with fragile X syndrome (FXS).

These adaptations improved the sensitivity and specificity of both tests, yet are not enough to accurately diagnose autism among fragile X patients, they reported. Combining both revised scales with clinical diagnostic criteria, however, can identify a group of patients at greater risk of irritability, aggression and mood problems, issues that are often overlooked in this population.

The study, “Improving the Diagnosis of Autism Spectrum Disorder in Fragile X Syndrome by Adapting the Social Communication Questionnaire and the Social Responsiveness Scale-2,” was published in the Journal of Autism and Developmental Disorders.

Autistic behaviors are a common feature of fragile X — the most frequent single-gene cause of ASD — and are estimated to affect between 30% and 54% of male patients. They are linked to greater cognitive and behavioral impairments.

As with other genetic forms of intellectual disability, a diagnosis of ASD in fragile X is challenging, especially given frequent problems in social communication and interaction.

Still, a timely diagnosis of ASD in people with fragile X is essential to making an early impact on possible outcomes.

The gold standard for ASD diagnosis in the U.S. is the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria, developed by the American Psychiatric Association. According to these guidelines, a rigorous diagnosis requires that clinicians combine clinical observation with additional measures, including standardized instruments, educational reports, and detailed caregiver interviews.

Some of the best instruments used, however, require extensive training and take significant time to administer. Their accuracy is also affected by challenging behaviors, developmental level, and overlapping symptoms with other neuropsychiatric disorders.

To develop a better ASD diagnostic tool specifically for fragile X patients, researchers focused on optimizing two instruments already used for ASD screening: the social communication questionnaire (SCQ) and the social responsiveness scale (SRS-2).

SCQ is a questionnaire where caregivers rate a patient’s developmental history and current behavior, while SRS-2 is a survey for parents, caregivers or teachers that measures social ability in children.

Scientists selected these scales because they are easy to use in a clinical setting, and they have better validity compared to other screening instruments.

To optimize each instrument for fragile X specifically, researchers used one of the largest fragile X datasets — the FORWARD Registry & Database, a patient/family registry and a longitudinal database using clinician- and parent-reported data.

In total, the study sample included 179 people with fragile X and ASD as well as 225 individuals with fragile X only, ages 4 to 51.

Using this data, researchers preformed evaluations of each original test, observing that both “performed poorly in a [fragile X] population using typical cut points.”

They then created modified versions of each scale — called fxSCQ and fxSRS — by removing specific questions considered unhelpful to diagnosing ASD in fragile X patients.

fxSCQ was shortened to 25 out of the 39 original items in the SCQ questionnaire, and fxSRS contained 46 of the 65 items in the SRS-2 scale. Those changes resulted in the best combination of sensitivity and specificity — 79% and 59% for fxSCQ, respectively, and 69% and 66% for fxSRS.

“[B]oth revised instruments … demonstrated improved diagnostic features, with respect to the original versions of the measures, when applied to a [fragile X] population,” the researchers wrote.

The team also proposed new item groups it called “factors.” The revised fxSCQ questionnaire comprised three factors — restricted and repetitive behavior, social interest, and socio-emotional reciprocity — while fxSRS covered pragmatic language, relationships with peers, rigidity, social motivation, and nonverbal communication.

Despite an improvement in diagnostic ability, researchers stress that such revised measures “are still suboptimal for [fragile X].”

However, the team found that combining fxSCQ and fxSRS with DSM criteria (clinical diagnosis) — dubbed “triple criteria” — further improved the diagnostic specificity and enabled the identification of a distinct group of patients.

“Our findings suggest that males with triple criteria are at risk of specific behavioral problems, including irritability/aggression and mood problems, of which the latter are frequently overlooked. Recognition of this profile may help in developing targeted approaches to prevention and management of these problems,” the researchers wrote.

The revised scales reported here “may be informative for clinical and research evaluations of ASD in [fragile X], particularly in the characterization of impairments in social communication and social motivation,” they added. But additional work is necessary to validate and optimize both scales.