Profile of Behavioral Comorbidities in Children With Fragile X Syndrome

Fragile X syndrome (FXS) presents with a variety of behavioral comorbidities. Although multiple publications have reported detailed characterizations for some of them, many gaps of knowledge still remain. Therefore, we characterized the eight most common behavioral comorbidities (i.e., clinician identified behavioral concerns) in children evaluated in specialty FXS clinics.

We analyzed the pediatric FORWARD clinic-based natural history study database (1,072 males, 338 females), using multiple statistical techniques including chi-square analyses, polychoric and polyserial correlations, and Mann-Whitney tests to determine frequency, co-occurrence, and behavioral scale profiles of children with eight behavioral comorbidities and functional impairment (approximately half of those affected). DSM-5 criteria were only used for autism spectrum disorder (ASD) identification.

Attention problems and Anxiety were the two most common and mildest comorbidities, while disruptive behavior (IAAS) . Co-occurrence of impairing behavioral comorbidities were reported for 69% of children, with 39% of them presenting with more than two comorbidities and overall greatest impairment. Comorbidity co-occurrence was influenced by frequency, but strength of association was relatively independent. Strong correlations were found for two distinctive co-occurrences in non-FXS populations: Attention problems-Hyperactivity and Anxiety-Mood disturbances. Although scale scores aligned with other severity parameters, comorbidity-scale correlations reflected relevance of evaluated behaviors. Surprisingly, all behavioral comorbidities were strongly correlated with the Sensory problems scale.

The reported profiles of impairing behavioral comorbidities could assist clinicians in early identification of behavioral symptoms and in refining their management in children with FXS and, perhaps also, other neurodevelopmental disorders.