Clinical Insights into the Similarities and Differences for Diagnosis and Treatment

While it has long been known that individuals with Fragile X syndrome (FXS) often exhibit characteristics of autism spectrum disorder (ASD), only recently has the possibility been raised that the two conditions may have considerably more overlap than previously thought. Scientists at various Fragile X centers are studying whether this overlap may extend beyond mere behavioral similarities and perhaps include genetic or biological components as well. That research may prove to have far-reaching effects.

Meanwhile, parents, educators, and clinicians in the FX field have continued to note the similarities and differences between the two conditions so they can plan appropriate interventions based on the specific characteristics and needs of each individual. It was in that spirit that a well-attended panel discussion at the 13th International Fragile X Conference in Miami pondered the topic: FXS and ASD: Clinical Insights into the Similarities and Differences for Diagnosis and Treatment.

The discussion provided clinical perspectives on the behavioral differences between FXS and what are thought to be core features of ASD. There is still much to be learned about identifying behaviors that suggest the presence or absence of ASD in FXS.

As the science advances, researchers and clinicians will achieve a deeper understanding of the overlap between the two conditions, and how that overlap affects both of them. Moderator Vicki Sudhalter, PhD, led a distinguished panel of clinicians that included Tracy Stackhouse, MA/OTR, Sarah Scharfenaker, MA-CCC-SLP, Walter Kaufman, MD, and Richard Belser, PhD. Here are the key points that came out of the panel discussion:

  • Fragile X syndrome causes a range of functioning across domains. It is a specific, identifiable condition with a known genetic cause. Autism spectrum disorder is identified by a cluster of symptoms rather than a specific condition, and is believed to have many causes, most of them unknown. There is overlap, in that some individuals with FXS have ASD, and some do not, though FXS is known to be the leading known single gene cause of ASD.
  • Clinicians must understand the differences between the two conditions in order to avoid misdiagnosis and improper treatment. Likewise, clinicians must appreciate the similarities. Harnessing what is known about ASD in particular, given its larger cache of treatment strategies, can help advance treatment and educational plans as appropriate.
  • The core deficit in ASD is social interaction. The core deficit in FXS is intellectual function and hyperarousal/anxiety. A key point related to these differences: People with FXS tend to be deeply desirous of human interaction, but the social anxiety that also typifies the condition often causes them to act otherwise, which prevents success. People with ASD are largely unaware of the function others serve in relation to themselves, hence they rarely seek social interaction.
  • Eye contact is a key element of social interaction, and though “poor” eye contact is symptomatic of both FXS and ASD, the type of eye contact is substantially different. People with FXS tend to avoid eye contact, looking off in another direction to cope with their social anxiety, while people with ASD are unaware of why they should use eye contact as a source of information or interaction. Insisting on eye contact with those who have FXS is most always counterproductive, leading to greatly heightened anxiety.
  • Even when avoiding eye contact, people with FXS tend to be acutely aware of their surroundings. Like a good politician or salesperson, a person with FXS can read a room effectively, accurately gauging others’ moods and anxiety levels. They long to participate, to joke and be joked with. They want to be inside a social circle-but they typically need a great deal of acceptance, invitation and training to be successful at it. In contrast, people with ASD more often really do want to be left alone.
  • Imitation is generally a strength for those with FXS and not often seen in people with ASD. If imitation is not seen in those with FXS, it should be an impetus to conduct additional testing and treatment plans.
  • Teachers and caregivers often say they don’t need to know about FXS because they have previously had children with ASD in their classes or homes. But interventions appropriate for children with FXS may be quite different from those appropriate for children with ASD. For example, a shaping procedure is often used to increase eye contact in children with ASD. In contrast, our experience with children with FXS has shown us that working to increase eye contact in this population can be counterproductive.
  • Both FXS and ASD are typified by repetitive behaviors, but in FXS, this is most commonly manifested as hand-flapping and body-stiffening. Those with FXS tend to exhibit repetitive behaviors due to excitement, anxiety, or difficulty “stopping” or inhibiting their behavior. People with ASD engage in those behaviors as well, but for more varied reasons.
  • At base, most FXS behavioral issues are traceable to the twin challenges of managing anxiety and hyperarousal. Autism spectrum disorder is more complex and multi-faceted in its behavioral roots and manifestations, thereby making it essential to delineate the function of the behavior before formulating a treatment plan.
  • The crucial point for teachers, therapists, and others involved in the care of those with FXS is not to lump them in with ASD as more or less a common diagnosis requiring a common set of interventions. Fragile X syndrome is still best treated utilizing what is known specifically about the condition.


Fragile X Syndrome & Autism »
When associated with FXS, autism is caused by the genetic change or mutation in the Fragile X gene—the most common genetic cause of autism.

A Blood Test for Autism? Not so Fast »
The notion that autism itself can be directly diagnosed through a blood test is incorrect and misleading.

Autism Spectrum Disorder in Fragile X Syndrome: Cooccurring Conditions and Current Treatment »
This study examines the impact of the ASD diagnosis in a large clinic-based FXS population to better inform the care of people with FXS. (Pediatrics, June 2017, Vol. 139)