Assessment of Social Interaction in FXS

Evaluating Social Interactions Using the Autism Screening Instrument for Education Planning-3rd Edition (ASIEP-3): Interaction Assessment in Children and Adults with Fragile X Syndrome.

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ABSTRACT

An efficient and direct measure of social interactions and autism symptoms is needed for fragile X syndrome (FXS) research and clinical care. The Autism Screening Instrument for Educational Planning-Third Edition (ASIEP-3) Interaction assessment is a brief standardized measure that quantifies social responses under different conditions. The feasibility and validity of the ASIEP-3 was evaluated in 26 males and 13 females with FXS, along with cognitive testing and behavior questionnaires. The videos were scored at 10-second intervals, and the observed behaviors were scored as an interaction, independent play, no response, or aggression. In total, 39/41 participants successfully completed the ASIEP-3 (age M = 14.4 ± 10.2), with a range of cognitive abilities (abbreviated IQ (ABIQ) M = 58.9 ± 17.3, median = 50), behaviors (Aberrant Behavior Checklist (ABC) Total M = 37.00 ± 27.3), and autism diagnoses (N = 22/39). Reliable administration was demonstrated by all team members. The mean coded behaviors included interaction (40.6%), independent play (36.8%), no response (21.1%), and aggressive behavior (<10%). The interaction score was negatively correlated with the Social Communication Questionnaire (SCQ) score (p = 0.037), and the profiles differed by autism spectrum disorder (ASD) diagnosis. The intraclass correlation coefficients (ICCs) ranged from 0.79 to 0.93 for master’s level and above. Administration of the ASIEP-3 was feasible for FXS across sex, age, ability, and behavior ratings by a trained research team. Reliable scoring required advanced training in the assessment of social development and FXS experience. The scores correlated to ratings and diagnoses of ASD. The ASIEP-3 shows promise to reliably index social interactions in FXS.

Cordeiro, L.; Braden, M.; Coan, E.; Welnick, N.; Tanda, T.; Tartaglia, N. Evaluating Social Interactions Using the Autism Screening Instrument for Education Planning-3rd Edition (ASIEP-3): Interaction Assessment in Children and Adults with Fragile X Syndrome. Brain Sci. 202010, 248.

Repetitive Behaviors in FXS

Delineating Repetitive Behavior Profiles across the Lifespan in Fragile X Syndrome.

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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.

Reisinger, D.L.; Shaffer, R.C.; Tartaglia, N.; Berry-Kravis, E.; Erickson, C.A. Delineating Repetitive Behavior Profiles across the Lifespan in Fragile X Syndrome. Brain Sci. 202010, 239.

FXS & Language Across the Lifespan

Language across the Lifespan in Fragile X Syndrome: Characteristics and Considerations for Assessment

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ABSTRACT

While it is widely acknowledged that language development is delayed for the majority of individuals with fragile X syndrome (FXS), there has been limited research into how best to assess this area. This study aimed to deepen the understanding of standardized language assessment in FXS by addressing the three following objectives: (1) Examine the feasibility and validity of widely-used, standardized assessments in participants with FXS; (2) describe linguistic and cognitive profiles for a large sample of individuals with FXS; and (3) Compare results obtained from objective testing in clinic to those obtained using caregiver report.

Results indicate that previous results indicating strong correlations between cognition and language results hold true across a wide range of ages as well as across multiple assessments, with an exception in very young children. Caregiver report tended to give lower estimates of language ability than what was found using an objectively administered assessment. Appropriate assessments remain difficult to find as a significant percentage of individuals scored at floor when scaled scores were calculated. Further, a sub-group of participants were coded for behavioral response to testing demands, the majority being able to complete a standardized assessment. These results speak to the need for assessments that provide a wider range of items so individuals can both achieve a valid score and demonstrate progress in their attainment of language skills.

Hoffmann, A.; Wang, A.; Berger, N.; Cordeiro, L.; Shaffer, R.; Tartaglia, N.; Erickson, C.; Berry-Kravis, E. Language across the Lifespan in Fragile X Syndrome: Characteristics and Considerations for Assessment. Brain Sci. 202010, 212.

Health-related quality of life in FXS

Examination of Correlates to Health-Related Quality of Life in Individuals with Fragile X Syndrome.

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ABSTRACT

Health-related quality of life (HRQoL) is a multidimensional concept involving physical, psychological, social, and cognitive aspects of life. Individuals with Fragile X syndrome (FXS) experience a life-long disorder that impacts the HRQoL of the affected individual and their family. Thus, HRQoL may be an important outcome measure following intervention. However, it is yet not known whether HRQoL concerns relate to observed impairments in FXS. In the present study, we examined the nature and degree of association between HRQoL and established measures of functioning in FXS using the Parent Report for Children version of the PedsQL 4.0 Generic Core Scales and Cognitive Functioning Scale. We observed significant relationships between HRQoL and measures of adaptive behavior, maladaptive behaviors, and social functioning. The present study has implications for treatment outcomes for clinical trials in FXS.

Coffman, M.C.; Shaffer, R.C.; Schmitt, L.M.; Dominick, K.C.; Pedapati, E.; Wang, A.; Berry-Kravis, E.; Tartaglia, N.; Erickson, C.A. Examination of Correlates to Health-Related Quality of Life in Individuals with Fragile X Syndrome. Brain Sci. 202010, 213.

Toilet Training in FXS

Toilet Training in Fragile X Syndrome.

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Summary: Toilet training issues can be burdensome and a significant problem for families with children affected by Fragile X Syndrome (FXS). This groundbreaking study utilized FORWARD data on 633 individuals with FXS to fill the gap for much needed information on when children with FXS learn bladder and bowel toileting skills. By characterizing toileting milestones in children with FXS, this study helps to shed light on the factors causing delays in toilet training.

Language, behavioral irritability and autism spectrum diagnoses (ASD) presented as the main factors in predicting bowel and bladder training delays. ASD diagnosis and gender had a strong impact on age of toilet training. Males and individuals with a co-diagnosis of ASD showed a significant delay in learning toilet training skills. By 5 years of age, almost 100% of females achieve bladder toilet training versus 70% of females with a co-diagnosis of ASD. In comparison, about 50% of males with FXS alone achieved bladder training by age 5 and over 90% achieved toilet training by age 10, while 35% of males with a co-diagnosis of ASD achieved bowel toilet training by age 5 and about 60% by age 10. Across all the groups in a multi-variate analysis, more impaired language/communication was the single most important predictor of the length of toileting delay.

Why this is important: This important study will allow practitioners to inform families about the typical toilet training process and what to expect with toilet training efforts in a thoughtful, informed and encouraging manner. These findings will help providers develop and evaluate specifically targeted toilet training approaches based on gender, ASD diagnosis and other clinical features identified in this study.

What are the next steps: The data presented in this report will serve as an important reference for evaluating the effectiveness of new toileting interventions in future research.

Age is shown on the horizontal line at the bottom of the graph. This is plotted against the proportion of individuals toilet trained at a given age (eg. 0.6 would mean 6 of 10 or 60% of individuals are trained).

Berry-Kravis, E. (2019). Toilet Training in Fragile X Syndrome. Journal of Developmental & Behavioral Pediatrics. 40(9), 751-761.

Preventive care services in FXS

Preventive care services and health behaviors in children with fragile X syndrome.

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Published in Disability and Health Journal, researchers from the Centers for Disease Control and Prevention and other organizations presented FORWARD data on preventive services received by children and young adults with FXS. This research can help clinicians identify preventive care services that patients with FXS may need.

Key findings:

  • Only one in four children and young adults with FXS met the physical activity guidance from the United States Department of Health and Human Service (DHHS). DHHS recommends children 6–17 years of age get one hour of physical activity every day, while adults need about 2.5 hours per week.
  • Slightly more than half of the children and young adults with FXS met the CDC recommendation for an annual influenza vaccination.
  • Almost three out of four children and young adults with FXS met dental care guidance from the American Academy of Pediatric Dentistry (AAPD). The AAPD recommends children have their first dental exam at the time of their first tooth eruption, or by one year of age, followed by regular exams every 6 months for children and adults.
  • About nine out of ten children and young adults with FXS received the immunizations recommended by CDC between birth and 18 years of age.

Gilbertson K, et al. (2019). Preventive care services and health behaviors in children with fragile X syndrome. Disabil Health J. 12, 564-573

Drug Interventions for IAAS in FXS

Pharmacologic Interventions for Irritability, Aggression, Agitation and Self-Injurious Behavior in Fragile X Syndrome: An Initial Cross-Sectional Analysis.

Behavioral dysregulation, or the impairment of behavioral processes, is common in FXS. A regularly cited group of behaviors in individuals with FXS, particularly males, is irritability, agitation, aggression and self-injurious (IAAS) behaviors. These behaviors can put a strain on both the individual and their caregiver’s quality of life and there is little information about how to manage these behaviors with medication. This publication in the Journal of Autism and Developmental Disorders presented information from a FORWARD dataset involving 415 individuals with IAAS behaviors. The study describes the psychopharmacologic management of IAAS and examines the characteristics of individuals that are treated with drug therapy for IASS.

Findings showed that among the individuals with FXS that were exhibiting IAAS, those receiving drug treatment were more likely to be older males with significant intellectual disability. The individuals receiving drug treatment were also more likely to have comorbid autism, anxiety, hyperarousal and social impairment. The medications most used in this population are antipsychotic medications, particularly Aripiprazole and Risperidone. Both Aripiprazole and Risperidone are FDA-approved for treating irritability associated with ASD. Individuals were also prescribed drugs outside of antipsychotic medications, including Selective serotonin reuptake inhibitors (SSRIs), stimulants, non-SSRI antidepressants, alpha-agonists, mood-stabilizers, and anxiolytics.  Most individuals (63%) did not experience side effects from their drug treatment.

Eckert EM, et al. (2019). Pharmacologic interventions for irritability, aggression, agitation and self-injurious behavior in fragile X syndrome: an initial cross-sectional analysis. J Autism Dev Disord. 49, 4595-4602

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ASD Diagnosis in FXS

Improving the Diagnosis of Autism Spectrum Disorder in Fragile X Syndrome by Adapting the Social Communication Questionnaire and the Social Responsiveness Scale-2.

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This paper published in the Journal of Autism and Developmental Disorders addresses the difficulty of diagnosing ASD in FXS. Although individuals with FXS are commonly diagnosed with ASD, it is a challenging diagnosis because intellectual disability and co-occurring mental health conditions can be interpreted as autistic features. Two commonly used standard measures, the Social Communication Questionnaire (SCQ) and the Social Responsiveness Scale (SRS), were examined as potential tools for improving ASD diagnosis and characterization in FXS. Researchers scientifically analyzed the SCQ and SRS and compared it to the standard DSM5 method used across clinicians to diagnose ASD in FXS. To improve diagnostic accuracy of ASD, various methodological revisions were applied to the SCQ and SRS in order to improve sensitivity and specificity of the measures.

Although the revised SCQ and SRS have an improved sensitivity/specificity balance and may be better suited for identifying ASD in males with lower cognitive function and irritability/aggression, the diagnostic accuracy of these measures is still below optimal levels, reflecting to some extent the inherent difficulty of diagnosing ASD in intellectual disability. This research suggests there are differences between the diagnosis of FXS and FXS+ASD. More work needs to be done to examine additional modifications, beyond deletion of non-informative items, that can further improve the diagnostic potential of the SCQ and SRS in FXS.

Kidd SA, et al. (2019). Improving the Diagnosis of Autism Spectrum Disorder in Fragile X Syndrome by Adapting the Social Communication Questionnaire and the Social Responsiveness Scale-2. J Autism Dev Disord. 2019, 1-20. doi: 10.1007/s10803-019-04148-0

Early Life Language Development in FXS

A Pilot Quantitative Evaluation of Early Life Language Development in Fragile X Syndrome.

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ABSTRACT

Language delay and communication deficits are a core characteristic of the fragile X syndrome (FXS) phenotype. To date, the literature examining early language development in FXS is limited potentially due to barriers in language assessment in very young children. The present study is one of the first to examine early language development through vocal production and the language learning environment in infants and toddlers with FXS utilizing an automated vocal analysis system. Child vocalizations, conversational turns, and adult word counts in the home environment were collected and analyzed in a group of nine infants and toddlers with FXS and compared to a typically developing (TD) normative sample. Results suggest infants and toddlers with FXS are exhibiting deficits in their early language skills when compared to their chronological expectations. Despite this, when accounting for overall developmental level, their early language skills appear to be on track. Additionally, FXS caregivers utilize less vocalizations around infants and toddlers with FXS; however, additional research is needed to understand the true gap between FXS caregivers and TD caregivers. These findings provide preliminary information about the early language learning environment and support for the feasibility of utilizing an automated vocal analysis system within the FXS population that could ease data collection and further our understanding of the emergence of language development.

Reisinger, D.L.; Shaffer, R.C.; Pedapati, E.V.; Dominick, K.C.; Erickson, C.A. A Pilot Quantitative Evaluation of Early Life Language Development in Fragile X Syndrome. Brain Sci. 20199, 27.

FORWARD: Study of FXS

FORWARD: A Registry and Longitudinal Clinical Database to Study Fragile X Syndrome.

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ABSTRACT

BACKGROUND AND OBJECTIVE:

Advances in the care of patients with fragile X syndrome (FXS) have been hampered by lack of data. This deficiency has produced fragmentary knowledge regarding the natural history of this condition, healthcare needs, and the effects of the disease on caregivers. To remedy this deficiency, the Fragile X Clinic and Research Consortium was established to facilitate research. Through a collective effort, the Fragile X Clinic and Research Consortium developed the Fragile X Online Registry With Accessible Research Database (FORWARD) to facilitate multisite data collection. This report describes FORWARD and the way it can be used to improve health and quality of life of FXS patients and their relatives and caregivers.

METHODS:

FORWARD collects demographic information on individuals with FXS and their family members (affected and unaffected) through a 1-time registry form. The longitudinal database collects clinician- and parent-reported data on individuals diagnosed with FXS, focused on those who are 0 to 24 years of age, although individuals of any age can participate.

RESULTS:

The registry includes >2300 registrants (data collected September 7, 2009 to August 31, 2014). The longitudinal database includes data on 713 individuals diagnosed with FXS (data collected September 7, 2012 to August 31, 2014). Longitudinal data continue to be collected on enrolled patients along with baseline data on new patients.

CONCLUSIONS:

FORWARD represents the largest resource of clinical and demographic data for the FXS population in the United States. These data can be used to advance our understanding of FXS: the impact of cooccurring conditions, the impact on the day-to-day lives of individuals living with FXS and their families, and short-term and long-term outcomes.

Sherman SL, et al. Fragile X Online Registry With Accessible Research Database (FORWARD): Experience from the Fragile X Clinical and Research Consortium to study the natural history fragile X syndrome. Pediatrics 2017;139 (Suppl 3):S183-S193