Relationship Between Intellectual Disability and Behavioral Comorbidity in Children with Fragile X Syndrome

This research looked at how a child’s level of intellectual disability (ID) — meaning how much their thinking and learning abilities are affected — relates to the types of behavioral challenges they experience if they have Fragile X syndrome (FXS).

FXS is the most common inherited cause of intellectual disability and autism. Children with FXS often show a wide range of strengths and challenges, some have mild learning differences, while others are more severely affected. Behavioral challenges like anxiety, hyperactivity, aggression, and autism-like traits are also common, but not all children experience them in the same way.

This paper aimed to better understand how these behaviors vary with cognitive ability. In other words, researchers asked: does the level of intellectual disability make certain behaviors more likely?

To answer this question, researchers used data from 1,400 children (1,072 boys, 338 girls) who took part in the FORWARD study, a large, long-term research project involving families across 25 Fragile X specialty clinics in the U.S. Families and doctors filled out questionnaires and checklists about each child’s learning abilities, daily functioning, and behaviors.

Researchers grouped children into five behavioral “subtypes” based on patterns seen in the data — from mild to severe — and compared behavioral issues across levels of intellectual disability.

What They Found

Researchers found that certain behaviors are more common in children with more severe intellectual disability. These behaviors include: autism features, aggressive or self-injurious behaviors, repetitive or obsessive behaviors, and sensory hypersensitivity (strong reactions to sound, touch, etc.).

Other behaviors, like anxiety or ADHD-like symptoms, didn’t depend on ID level. Children with Fragile X of any ability level could experience anxiety or attention problems — these are common across the board.

Additionally, kids with milder ID generally had fewer and less severe behavior problems, while those with more significant ID were more likely to have multiple challenges together (like ASD and self-injury).

This research helps explain why every child with Fragile X is unique — and why some behaviors show up more often in children with greater learning challenges.

For families and doctors, understanding this pattern can:

• Help anticipate which behaviors may arise as a child develops.
• Support more personalized care and behavior management strategies.
• Clarify that not all behavioral difficulties come from intellectual disability — issues like anxiety or attention can affect anyone with FXS, regardless of IQ.

Ultimately, this kind of large-scale data helps guide better treatment, support, and early intervention for children with Fragile X and their families. Researchers will continue studying how learning and behavior change over time in children with FXS, helping identify early signs and more personalized support for each child.

The present study was supported by cooperative agreements funded by the Centers for Disease Control and Prevention (CDC). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the CDC or the Department of Health and Human Services.

De-identified data are available according to the FORWARD project’s Data Sharing Plan and the policies of the Centers for Disease Control and Prevention.