Delineating Repetitive Behavior Profiles across the Lifespan in Fragile X Syndrome

Abstract

Restricted repetitive behaviors (RRBs) are a core area of impairment in autism spectrum disorder (ASD), but also affect several other neurodevelopmental disorders including fragile X syndrome (FXS). Current literature has begun to describe the RRB profile in FXS up through adolescence; however, little is known about the subtypes of RRBs in adolescents and adults. Further, literature on the RRB profile of females with FXS is limited. The present study examines the RRB profile across subtypes and specific items in both males and females with FXS while assessing for differences based on age, ASD diagnosis and the impact of IQ. Participants included 154 individuals with FXS (ages 2 to 50 years old). Results revealed a peak in RRB severity in FXS between 7–12 years for the majority of RRB subscales with the exception of Sensory-Motor behaviors peaking between 2 and 12 years before declining. Distinct RRB profiles in males and females with FXS emerged in addition to significant overlap among the item and subscale levels of RRBs across gender. Further, an added diagnosis of ASD significantly increased rates of RRBs across all subscale levels, but not necessarily across all items. Lastly, IQ did not solely account for the presence of RRBs in FXS, with Sensory-Motor behaviors being driven by comorbid ASD in males with FXS, and Restricted Interest behaviors being driven by comorbid ASD regardless of gender. These findings build on the current understanding of RRBs in FXS based on gender and comorbid ASD and lay important groundwork for the development of targeted behavioral and pharmacological treatments.

Behavior Problems and Social Competence in Fragile X Syndrome: A Systematic Review

“…This worse profile of behavior problems mainly comprised behaviors that could be included under externalizing behaviors [ 157 ], such as hyperactivity, aggression or irritability, and repetitive behaviors, although greater attention problems have also been reported in individuals with comorbid ASD. Other studies support this worsening profile, showing generally greater problems in males with FXS+ASD than in those with FXS only [ 158 ], in addition to increasing rates of repetitive behaviors in individuals with FXS with comorbid ASD in comparison to those with FXS only [ 159 ]. Furthermore, higher rates of challenging behavior were exhibited for comorbid individuals with FXS+ASD compared to those with FXS only [ 160 ].…”

Gaboxadol in Fragile X Syndrome: A 12-Week Randomized, Double-Blind, Parallel-Group, Phase 2a Study

“…With an estimated prevalence of approximately 1 in 4,000 males and 1 in 6,000 females, FXS is the most common single-gene cause of intellectual disability (ID) and autism spectrum disorder (ASD) (Crawford et al, 2001;Tassone et al, 2012). Individuals with FXS can present with a broad range of neurobehavioral abnormalities, including cognitive deficits e.g., ID, 95% of males, 35% of females (Rousseau et al, 1994;Wright-Talamante et al, 1996); language disorders (non-verbal to perseverative); ASD (51% of males); psychiatric and behavioral impairments, such as anxiety, hyperarousal, and other sensory processing difficulties; repetitive behaviors; attentional network deficits; and irritability often accompanied by aggressive and/or self-injurious behaviors (Hagerman et al, 2009;Kaufmann et al, 2017;Raspa et al, 2018;Budimirovic et al, 2020;Reisinger et al, 2020). Patients with FXS also present with neurological abnormalities, such as motor and coordination difficulties (Gabis et al, 2011) and a higher incidence of epilepsy (Hagerman et al, 2009).…”

Social communication in fragile X syndrome: pilot examination of the Brief Observation of Social Communication Change (BOSCC)

“…The more variable test-retest values paired with the lower inter-rater reliability for RRB also suggests that RRBs may present differently in FXS versus idiopathic ASD. Reisinger et al [43] found a peak in sensory-motor RRB severity between the ages of 2 and 12 and other RRBs between ages 7 and 12. These results may also suggest that the validity of coding of the RRBs in FXS may require specialized training in FXS and associated behaviors.…”

“…In comparison with other genetic syndromes, individuals with FXS demonstrate more RRBs [40] and in comparison, to youth with idiopathic ASD, individuals with co-occurring FXS and ASD demonstrate equal amounts of less complex forms of RRB's such as body and hand movements [59]. A recent study across a wide age range in FXS found that sensory related RRBs are more common in young children but other forms of RRBs tend to remain stable across ages [43]. Additionally, caregivers reported most concerns with transition difficulties and hand and finger mannerisms.…”