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Objective: The Aberrant Behavior Checklist (ABC) is a standardized rating scale used for assessing problematic behavior of individuals with developmental disabilities. It has five subscales: Irritability, Social Withdrawal, Stereotypic Behavior, Hyperactivity, and Inappropriate Speech. A previous study in individuals with fragile X syndrome (FXS) reported six factors, with the Social Withdrawal factor bifurcating into Socially Unresponsive and Social Avoidance factors, suggesting a different factor structure in people with FXS. Methods: We assessed the ABC's factor structure (with both exploratory and confirmatory analyses) in 797 people with FXS and we compared these findings with exploratory factors derived from an independent sample of 357 individuals with FXS. In an ancillary analysis, we compared the overlap of the traditional ABC's Social Withdrawal scores with the Social Avoidance scores from the FXS-derived newer scale to determine whether overlap between these was very high and essentially redundant. Finally, we computed norms using both the traditional and the FXS-specific algorithms. Results: In confirmatory factor analyses, the FXS-specific algorithm produced the most consistent factor structure for the sample of 797 participants, but model fit was only marginally better than that derived by the original ABC scoring algorithm. Comparisons of factor structures from separate exploratory analyses revealed no consistent advantage of the FXS algorithm over the traditional algorithm. While a Social Avoidance subscale did emerge in some analyses, in other analyses, this was accompanied by loss of coherence on other domains of interest, such as the Socially Unresponsive/Social Withdrawal subscale. Conclusion: We question whether the newer FXS scoring algorithm contributes data that are consistently helpful in evaluating behavior of people with FXS. In general, we recommend continued use of the original ABC algorithm for scoring behavior of clients with FXS. However, we acknowledge that there may be circumscribed times when the new algorithm may be appropriate for scoring, namely when anxiety and/or social avoidance constructs are the central and unequivocal domains of interest.

Background Previous research suggests that individuals with intellectual or developmental disabilities (IDD) may experience challenges accessing quality health care. Objective/Hypothesis This study explored parent perceptions of access and quality of health care services for children with fragile X syndrome (FXS), the leading hereditary cause of intellectual/developmental disabilities. Methods Nearly 600 primary caregivers of at least one child with FXS completed an online survey on access, barriers, and quality of health care for their family member with FXS (N = 731). Results In a convenience sample of well-educated and affluent caregivers, the majority did not report experiencing difficulties with access to services. Caregivers of younger children and those with lower family incomes reported greater challenges with health care access. Nearly 40% of caregivers indicated that their child's PCP was not as knowledgeable about FXS-related needs as they would prefer, indicating a possible knowledge gap on the part of providers. Conclusions These factors represent potential barriers to quality health care for individuals with FXS, with potential lifelong effects ranging from delayed age of diagnosis to difficulty accessing a PCP in adulthood.

Although informed consent is critical for all research, there is increased ethical responsibility as individuals with intellectual or developmental disabilities (IDD) become the focus of more clinical trials. This study examined decisional capacity for informed consent to clinical trials in individuals with fragile X syndrome (FXS). Participants were 152 adolescents and adults (80 males, 72 females) with FXS who completed a measure of decisional capacity and a comprehensive battery of neurocognitive and psychiatric measures. Females outperformed males on all aspects of decisional capacity. The ability to understand aspects of the clinical trial had the strongest association with the ability to appreciate and reason about the decision. Scaffolding improved understanding, suggesting researchers can take steps to improve decisional capacity and the informed consent process.

Prior to statewide newborn screening (NBS) for spinal muscular atrophy (SMA) in North Carolina, U.S.A., we offered voluntary screening through the Early Check (EC) research study. Here, we describe the EC experience from October 2018 through December 2020. We enrolled a total of 12,065 newborns and identified one newborn with 0 copies of SMN1 and two copies of SMN2, consistent with severe early onset of SMA. We also detected one false positive result, likely stemming from an unrelated blood disorder associated with a low white blood cell count. We evaluated the timing of NBS for babies enrolled prenatally (n = 932) and postnatally (n = 11,133) and reasons for delays in screening and reporting. Although prenatal enrollment led to faster return of results (median = 13 days after birth), results for babies enrolled postnatally were still available within a timeframe (median = 21 days after birth) that allowed the opportunity to receive essential treatment early in life. We evaluated an SMA q-PCR screening method at two separate time points, confirming the robustness of the assay. The pilot project provided important information about SMA screening in anticipation of forthcoming statewide expansion as part of regular NBS.

We describe the development of 236 children with Angelman syndrome (AS) using the Bayley Scales of Infant and Toddler Development, Third Edition. Multilevel linear mixed modeling approaches were used to explore differences between molecular subtypes and over time. Individuals with AS continue to make slow gains in development through at least age 12years of age at about 1-2months/year based on age equivalent score and 1-16 growth score points/year depending on molecular subtype and domain. Children with a deletion have lower scores at baseline and slower rate of gaining skills while children with UBE3A variant subtype demonstrated higher scores as well as greater rates of skill attainment in all domains. The developmental profiles of UPD and ImpD were similar.

Background Data from electronic health records (EHRs) are increasingly used in the field of genetic research to further precision medicine initiatives. However, many of these efforts exclude individuals with intellectual disabilities, which often stem from genetic conditions. To include this important subpopulation in EHR research, important ethical, legal, and social issues should be considered. Objective The goal of this study was to review prior research to better understand what ethical, legal, and social issues may need further investigation when considering the research use of EHRs for individuals with genetic conditions that may result in intellectual disability. This information will be valuable in developing methods and best practices for involving this group in research given they are considered a vulnerable population that may need special research protections. Methods We conducted a scoping review to examine issues related to the use of EHRs for research purposes and those more broadly associated with genetic research. The initial search yielded a total of 460 unique citations. We used an evaluative coding process to determine relevancy for inclusion. Results This approach resulted in 59 articles in the following areas: informed consent, privacy and security, return of results, and vulnerable populations. The review included several models of garnering informed consent in EHR or genetic research, including tiered or categorical, blanket or general, open, and opt-out models. Second, studies reported on patients’ concerns regarding the privacy and security of EHR or genetic data, such as who has access, type of data use in research, identifiability, and risks associated with privacy breach. The literature on return of research results using biospecimens examined the dissension in the field, particularly when sharing individualized genetic results. Finally, work involving vulnerable populations highlighted special considerations when conducting EHR or genetic research. Conclusions The results frame important questions for researchers to consider when designing EHR studies, which include individuals with intellectual disabilities, including appropriate safeguards and protections.

Children with fragile X syndrome (FXS) display wide-ranging intellectual and behavioral abilities that affect daily life. We describe the educational setting of students with FXS and assess the relationships between school setting, co-occurring conditions, and functional ability using a national survey sample (n = 982). The majority of students with FXS in this sample have formal individualized education plans, spend part of the day outside regular classrooms, and receive modifications when in a regular classroom. Males with FXS and certain co-occurring conditions (autism, aggression, and self-injurious behavior) are more likely to spend the entire day outside regular classrooms, compared to males without these co-occurring conditions. Students who spend more time in regular classrooms are more likely to perform functional tasks without help.

Migrating cells need to coordinate distinct leading and trailing edge dynamics but the underlying mechanisms are unclear. Here, we combine experiments and mathematical modeling to elaborate the minimal autonomous biochemical machinery necessary and sufficient for this dynamic coordination and cell movement. RhoA activates Rac1 via DIA and inhibits Rac1 via ROCK, while Rac1 inhibits RhoA through PAK. Our data suggest that in motile, polarized cells, RhoA–ROCK interactions prevail at the rear whereas RhoA-DIA interactions dominate at the front where Rac1/Rho oscillations drive protrusions and retractions. At the rear, high RhoA and low Rac1 activities are maintained until a wave of oscillatory GTPase activities from the cell front reaches the rear, inducing transient GTPase oscillations and RhoA activity spikes. After the rear retracts, the initial GTPase pattern resumes. Our findings show how periodic, propagating GTPase waves coordinate distinct GTPase patterns at the leading and trailing edge dynamics in moving cells.

This study sought to describe food- and non-food-related behaviors of children aged 3 to 18 years with Prader&ndash, Willi syndrome (PWS) in home and school settings, as assessed by 86 parents and 63 teachers using 7 subscales of the Global Assessment of Individual&rsquo, s Behavior (GAIB). General Behavior Problem, Non-Food-Related Behavior Problem, and Non-Food-Related Obsessive Speech and Compulsive Behavior (OS/CB) scores did not differ significantly between parent and teacher reports. Food-Related Behavior Problem scores were higher in parent versus teacher reports when the mother had less than a college education (difference of 13.6 points, 95% Confidence Interval (CI) 5.1 to 22). Parents assigned higher Food-Related OS/CB scores than teachers (difference of 5.7 points, 95% CI 2.4 to 9.0). Although teachers reported fewer Food-Related OS/CB, they scored overall OS/CB higher for interfering with daily activities compared with parents (difference of 0.9 points, 95% CI 0.4 to 1.4). Understanding how behaviors manifest in home and school settings, and how they vary with socio-demographic and patient characteristics can help inform strategies to reduce behavior problems and improve outcomes.

Although temperament has been studied for decades as a predictor of psychopathology in the general population, examining temperament in neurogenetic groups has unique potential to inform the genetic and biological factors that may confer risk for psychopathology in later development. The present study examined early temperament in two heritable neurogenetic conditions associated with atypical CGG repeat expansions on the FMR1 gene: the FMR1 premutation (FXpm; 55–200 repeats) and fragile X syndrome (FXS; >200 repeats). We focus specifically on the FXpm, as the condition is highly prevalent (1:209 females and 1:430 males) and associated with increased risk for pediatric psychopathology, including attention problems, autism, and anxiety. In contrast, FXS is a low-incidence disorder (1:4,000) often associated with intellectual disability and more severe co-occurring psychosocial conditions. Given information on infant clinical phenotypes in the FXpm and FXS is sparse, we aimed to characterize parent-reported infant temperament in infants with the FXpm (n=22) relative to FXS (n=24) and controls (n=24), assessed on 1–3 occasions each. Results suggested temperament in infants with the FXpm was largely typical, yet also resembled FXS in the negative affect domain, with trends toward suppressed negative affect in younger participants. In contrast, temperament features of infants with FXS consistently deviated from TD controls in both negative affect and surgency domains. These data suggest that FMR1 gene mutations are associated with atypical temperament that emerges as early as infancy, particularly among infants with FXS, warranting further study of whether temperament may index emergent clinical risks in these populations.

Background Little is known about how individuals with fragile X syndrome (FXS) and their families use technology in daily life and what skills individuals with FXS can perform when using mobile technologies. Methods Using a mixed-methods design, including an online survey of parents (n = 198) and a skills assessment of individuals with FXS (n = 6), we examined the experiences and abilities of individuals with FXS for engaging with mobile technology. Results Parents reported that individuals with FXS often used technology in their daily lives, with variations based on age of child, sex, autism status, depression, and overall ability. Parents frequently sought and shared FXS-related information online. Assessment data revealed that individuals with FXS demonstrated proficiency in interacting with technology. Conclusions Mobile technology is a tool that can be used in FXS to build skills and increase independence rather than simply for recreational purposes. Implications for using mobile technology to enhance healthcare decision making are discussed.

The association between Zika virus infection during pregnancy and severe birth defects in infants has led to worldwide attention focused on the mechanisms of the disease and the prevention of future exposure. Surveillance efforts around the world continue with the goal of identifying and monitoring all potentially exposed women and their newborns. For infants who were born with congenital Zika syndrome (CZS) and their families, an uncertain future awaits. As infants who were born with CZS during the most recent outbreak enter their second year of life, new developments in the outcomes of the condition continue to unfold, providing some insight into the likely long-term sequalae. In this article, I review the literature on emerging findings regarding the impact of CZS on the developing infant and provide some predictions regarding the long-term outcomes and lifetime needs of these children and their families.

Repetitive sensory motor behaviors are a direct target for clinical treatment and a potential treatment endpoint for individuals with intellectual or developmental disabilities. By removing the burden associated with video annotation or direct observation, automated detection of stereotypy would allow for longer term monitoring in ecologic settings. We report automated detection of common stereotypical motor movements using commercially available accelerometers affixed to the body and a generalizable detection algorithm. The method achieved a sensitivity of 80% for body rocking and 93% for hand flapping without individualized algorithm training or foreknowledge of subject’s specific movements. This approach is well-suited for implementation in a continuous monitoring system outside of a clinical setting.

The objectives were to describe the demographic characteristics of children with Fragile X syndrome (FXS) and to determine predictors of attendance at Fragile X (FX) clinics. Findings from the Community Support Network (CSN) and Our Fragile X World (OFXW) samples showed that children who attended FX Clinics were mostly male, high-school aged or younger, and white, non-Hispanic. Using logistic regression models, awareness about FX Clinic services, guardian education, and income (CSN), and child age, family income, and total number of co-occurring conditions (OFXW) were predictors of clinic attendance. Demographic and child characteristics accounted for a large portion of the explained variance. Importantly, symptom severity and parent knowledge about services were independent predictors beyond the demographic characteristics of families.

Background Angelman syndrome (AS) is a rare disorder with a relatively well-defined phenotype. Despite this, very little is known regarding the unmet clinical needs and burden of this condition, especially with regard to some of the most prevalent clinical features—movement disorders, communication impairments, behavior, and sleep. Main text A targeted literature review using electronic medical databases (e.g., PubMed) was conducted to identify recent studies focused on specific areas of the AS phenotype (motor, communication, behavior, sleep) as well as epidemiology, diagnostic processes, treatment, and burden. 142 articles were reviewed and summarized. Findings suggest significant impairment across the life span in all areas of function. While some issues may resolve as individuals get older (e.g., hyperactivity), others become worse (e.g., movement disorders, aggression, anxiety). There are no treatments focused on the underlying etiology, and the symptom-based therapies currently prescribed do not have much, if any, empirical support. Conclusions The lack of standardized treatment protocols or approved therapies, combined with the severity of the condition, results in high unmet clinical needs in the areas of motor functioning, communication, behavior, and sleep for individuals with AS and their families.

BACKGROUND: Fragile X syndrome (FXS) is the most common known inherited form of intellectual disability. Early identification is an important step in linking FXS individuals with appropriate and timely medical and social services. Newborn screening (NBS) is 1 approach that has been used for other conditions to facilitate early identification. METHODS: A literature review was conducted to identify issues, barriers, challenges, and approaches to addressing challenges related to NBS for FXS. Search terms included: fragile X syndrome, FMR1, newborn screening, screening, and genetic testing. To supplement the literature review, 9 key informant interviews were conducted. Information gathered through these interviews supplemented what was identified in the literature. Information from both the literature review and supplemental interviews was reviewed by 3 researchers who discussed and came to consensus on thematic areas and categorization of issues. RESULTS: The barriers and challenges related to NBS for FXS identified in the literature and by experts and stakeholders are categorized into 5 thematic areas: public health burden, treatment, timing, screening/testing methodologies, and translating results. Summaries of these issues and barriers are provided, along with potential approaches to addressing them. CONCLUSIONS: The issues and barriers described in this article highlight limited areas of knowledge that need be addressed to improve our understanding of FXS and the potential benefit of NBS. The landscape of NBS for FXS could be influenced by a series of research findings over time or a larger breakthrough that demonstrates an effective targeted treatment that has to be implemented early in life.

OBJECTIVES: The purpose of this systematic literature review is to describe what is known about fragile X syndrome (FXS) and to identify research gaps. The results can be used to help inform future public health research and provide pediatricians with up-to-date information about the implications of the condition for individuals and their families. METHODS: An electronic literature search was conducted, guided by a variety of key words. The search focused on 4 areas of both clinical and public health importance: (1) the full mutation phenotype, (2) developmental trajectories across the life span, (3) available interventions and treatments, and (4) impact on the family. A total of 661 articles were examined and 203 were included in the review. RESULTS: The information is presented in the following categories: developmental profile (cognition, language, functional skills, and transition to adulthood), social-emotional profile (cooccurring psychiatric conditions and behavior problems), medical profile (physical features, seizures, sleep, health problems, and physiologic features), treatment and interventions (educational/behavioral, allied health services, and pharmacologic), and impact on the family (family environment and financial impact). Research gaps also are presented. CONCLUSIONS: The identification and treatment of FXS remains an important public health and clinical concern. The information presented in this article provides a more robust understanding of FXS and the impact of this complex condition for pediatricians. Despite a wealth of information about the condition, much work remains to fully support affected individuals and their families.

Intellectual disability (ID) is defined by impairments in intellectual and adaptive functioning. As such, tools designed to assess these domains would theoretically be ideal outcome measures for treatment trials targeting core symptoms of ID. However, measures of intellectual and adaptive functioning have rarely been used as primary outcome measures to date and further study is needed regarding their usefulness to measure change. This area of inquiry is important because promising, mechanism-modifying treatments for conditions leading to ID are being initiated. To show efficacy, these treatments need to demonstrate an impact on core features of ID. After reviewing literature on this topic, we suggest solutions to several problems outlined, including use of out-of-age-range testing, alternative metrics, and development of new measures.

Newborn screening (NBS) occupies a unique space at the intersection of translational science and public health. As the only truly population-based public health program in the United States, NBS offers the promise of making the successes of translational medicine available to every infant with a rare disorder that is difficult to diagnose clinically, but for which strong evidence indicates that presymptomatic treatment will substantially improve outcomes. Realistic NBS policy requires data, but rare disorders face a special challenge: Screening cannot be done without supportive data, but adequate data cannot be collected in the absence of large-scale screening. The magnitude and scale of research to provide this expanse of data require working with public health programs, but most do not have the resources or mandate to conduct research. To address this gap, we have established Early Check, a research program in partnership with a state NBS program. Early Check provides the infrastructure needed to identify conditions for which there have been significant advances in treatment potential, but require a large-scale, population-based study to test benefits and risks, demonstrate feasibility, and inform NBS policy. Our goal is to prove the benefits of a program that can, when compared with current models, accelerate understanding of diseases and treatments, reduce the time needed to consider inclusion of appropriate conditions in the standard NBS panel, and accelerate future research on new NBS conditions, including clinical trials for investigational interventions. Clinicaltrials.gov registration # NCT03655223 . Registered on August 31, 2018.

A total of 679 families who had at least one child with fragile X syndrome (FXS) were recruited from a research registry to participate in a survey examining cascade testing and communication about FXS. Families had a total of 1117 children (804 males, 313 females). Most families (84 %) had tested all of their children. The main reason for not testing, which did not differ by gender or age of the child, was that the child did not show signs of FXS (68 %). Families talked with their children about FXS occasionally (47 %) although 16 % said they do not talk about it. Most families (66 %) had told their children their FXS status, with males and those with the premutation being less likely to be told test results. Of those that did not, 46 % said that they would tell their child when they were old enough to understand, whereas 34 % had either decided they would not tell or were not sure if or when they were going to tell. About a quarter of respondents (28 %) indicated that no extended family members had been tested, with income and communication about FXS being the strongest predictors. Results from this large scale survey provide important data on how families communicate about FXS and reasons testing is or is not sought. This information can be used by genetic counsellors in providing follow-up to families after a FXS diagnosis.

Background Health researchers are increasingly using electronic health records (EHRs) to study the health care needs of people with neurodevelopmental disorders (NDDs). However, little is known about the preferences of people with NDDs for sharing EHRs for research. Objective To explore preferences for sharing EHRs for research among young adults ages 18–40 who make their own legal decisions and who have autism spectrum disorder (ASD), fragile X syndrome (FXS), or no NDDs. Methods We conducted a qualitative study with seven focus groups: 2 ASD groups, 3 FXS groups, and 2 no-NDD groups. We asked participants about factors that could affect their willingness to share their EHRs for research: type of organization, type of information, study purpose, duration, contact frequency, return of results, benefits, and risks. We analyzed the qualitative data using directed content analysis. Results Participants with NDDs valued personally relevant and directly beneficial EHR research. Participants with NDDs expressed willingness to share sensitive data if the study was personally relevant. Most participants wanted to receive results, but only participants with FXS indicated it would affect their willingness to participate. Participants were concerned about privacy risks, discrimination, researcher misconduct, and financial conflicts of interest. Conclusion This study provides initial evidence suggesting that young adults with NDDs prefer EHR research that is personally relevant, benefits themselves and their communities, and is conducted in the context of trusting, reciprocal participant-researcher relationships. The findings point to the need for researchers to improve the informed consent process and to better engage individuals with NDDs in research.

Background Anxiety is considered a 'frequent' feature in the clinical criteria for Angelman syndrome; however, the nature and severity of anxiety symptoms have not been well characterised in this population. Anxiety behaviours, especially in response to separation from a preferred caregiver, have been described clinically but have not yet been explored empirically. Method This study used a combination of standardised and clinician-derived survey items to assess the frequency, nature and severity of behaviours associated with anxiety and separation distress in 100 individuals with Angelman syndrome. Family (e.g. income and maternal education) and individual (e.g. age, sex, genetic subtype, sleep difficulties and aggressive behaviours) variables were also gathered to assess possible predictors of higher anxiety levels. Approximately half of the sample was seen in clinic and assessed with standardised measures of development and daily functioning, allowing for an additional exploration of the association between anxiety symptoms and extent of cognitive impairment. Results Anxiety concerns were reported in 40% of the sample, almost 70% were reported to have a preferred caregiver and over half displayed distress when separated from that caregiver. Individuals with the deletion subtype and individuals who are younger were less likely to have anxiety behaviours. Sleep difficulties and aggressive behaviour consistently significantly predicted total anxiety, the latter suggesting a need for future studies to tease apart differences between anxiety and aggression or anger in this population. Conclusions Anxiety concerns, especially separation distress, are common in individuals with Angelman syndrome and represent an area of unmet need for this population.

Abnormal sensory processing is one of the core characteristics of the fragile X phenotype. Studies of young children with fragile X syndrome (FXS) and the FMR1 premutation have shown sensory challenges as early as infancy and into early childhood. This study sought to examine differences in sensory difficulties in children with an FMR1 premutation compared with children with FXS and typically developing children. We conducted an online survey of 176 parents of affected children (FXS or FMR1 premutation). Most respondents were mothers who are Caucasian (86%), have a 4-year college or graduate degree (68%), and are married (92%). Children ranged in age from 5 to 18, with a mean age of 13.0 years (3.3 SD). Participants completed the BBC Sensory Scales, a 50-item Likert-type scale (1 = Almost Always, 4 = Almost Never) comprised of 8 subscales that assessed auditory processing, visual processing, tactile processing, and eating and feeding behaviors. Mean scores were calculated for the items and each of the subscales. Non-parametric tests examined differences in child and family-level variables. Across all BBCSS subscales, children with an FMR1 premutation displayed more sensory challenges than typically developing children. For six out of the eight subscales, children with the full mutation had the lowest scores indicating more sensory challenges, but this was closely followed by children with an FMR1 premutation. Fragile X status was associated with seven of the eight subscales; children with an FMR1 premutation did not differ from children with FXS on any of the subscales but had more digestive problems than children with no fragile X. Gender, autism status, and family income were also related to sensory sensitivities. In conclusion, these data provide further evidence that some children with an FMR1 premutation experience sensory difficulties that are similar to children with FXS but different than typically developing children.

BACKGROUND: Individuals with fragile X syndrome (FXS), especially men, have long been described as presenting with significant behavioural challenges. Despite this known aspect of the phenotype, there has been little research exploring the prevalence, frequency, nature or consequences of aggressive behaviour in FXS. METHODS: This study used survey methodology to gather caregiver reports on the types, frequency and severity of aggressive behaviour in 774 individuals with FXS. RESULTS: Based on caregiver report, nearly all (>90%) male and female individuals were reported to have engaged in some aggression over the previous 12 months, with a third of male cases and slightly fewer than 20% of female cases being described as engaging in moderate to severe aggression or being diagnosed or treated for aggression. Further, aggressive behaviours in male individuals were serious enough that 30% had caused injuries to caregivers and 22% had caused injuries to peers or friends. Sensory issues and hyperactivity were significant predictors of the frequency of aggressive acts, while sensory issues and anxiety were predictive of the severity of aggression. Traditional behaviour management techniques as well as medication was described as the most common and successful treatment options. CONCLUSIONS: Aggressive behaviours are a significant concern for a subsample of both male and female individuals with FXS. Given that sensory concerns were predictive of both the frequency and the severity of aggression suggests these behaviours may be a reactive means of escaping uncomfortable situations. Language: en

The recent Zika outbreak and its link to microcephaly and other birth defects in infants exposed in utero have garnered widespread international attention. Based on the severity of birth defects the extent of impairment in these infants is expected to be profound; however, virtually nothing is known regarding the developmental and behavioral sequela of congenital Zika syndrome. This pilot study collected parent-reported patterns of development and sleep in 47 infants with confirmed congenital Zika syndrome who are being followed for clinical services at the Altino Ventura Foundation (FAV) in Recife, Brazil. With assistance from clinicians at FAV, caregivers completed Brazilian Portuguese versions of the Ages and Stages Questionnaire, 3rd edition (ASQ-3) and the Brief Infant Sleep Questionnaire (BISQ). All infants were between 13–22 months of age at the time of the assessment. At 16 months of age, none of the children displayed age appropriate developmental skills. Most (~ 75%) mastered some communication and gross motor skills at around a 6–8-month level. Communication and gross motor skills were relative strengths for the sample, while problem-solving and fine motor skills were relative weaknesses. Sleep was noted to be a problem for around 18% of the sample. In utero exposure to the Zika virus will have lifelong consequences for affected children and their families. Understanding the developmental and behavioral trajectories of affected infants will help identify appropriate family supports to improve quality of life.

Background Adaptive behaviors, such as functional academic and daily living skills, are critical for independence in adults with intellectual and developmental disabilities. However, little is known about these skills in fragile X syndrome (FXS), the most common form of inherited intellectual disability. Aims The purposes of this study were to describe the functional academic and daily living skills of males diagnosed with FXS across different age groups and compare skill attainment by autism status and other common co-occurring conditions. Methods and procedures We used survey methods to assess parent-reported functional academic and daily living skills in 534 males with FXS. Functional academic skills included time and schedules, money, math, reading, and writing skills. Daily living skills included hygiene, cooking, laundry and housekeeping, transportation, and safety skills. Outcomes and results Analyses examined functional academic and daily living skills in a cross-sectional sample of males between ages 5 and 67. Differences in skill attainment were found by child age, co-morbid autism status, total number of co-occurring conditions, and respondent education. Functional academic and daily living skills were predictive of community employment and independent living. Conclusions and implications These data provide important information on the mastery of both foundational and more complex adaptive skills in males with FXS. Both functional academic and daily living skills were predictive of measures of independence above and beyond other child and family characteristics. These findings point to the need to focus interventions to support the attainment of independence in males with FXS.

Objective A higher rate of depressive symptoms is found among mothers of children with disabilities compared to other parents. However, there is a lack of study of mothers with children

Background Informed consent requires that individuals understand the nature of the study, risks and benefits of participation. Individuals with intellectual disabilities (ID) have cognitive and adaptive impairments that may affect their ability to provide informed consent. New treatments and clinical trials for fragile X syndrome, the most commonly known inherited cause of ID, necessitate the development of methods to improve the informed consent process. The goal of this study was to compare the efficacy of a digital decision support tool with that of standard practice for informed consent and to examine whether the tool can improve decisional capacity for higher functioning individuals. Methods Participants (N = 89; mean age = 21.2 years) were allocated to the experimental group (consenting information provided via the digital decision support tool), or the comparison group (information provided via standard practice). Participants were assessed on four aspects of decisional capacity (Understanding, Appreciating, Reasoning, and Expressing a choice). We used regression analyses to test the impact of the tool on each outcome, repeating the analyses on the higher functioning subsample. Results No differences existed in any domain of decisional capacity for the sample in full. However, participants in the higher IQ subsample who used the tool scored better on Understanding after adjustment (β = 0.25, p = 0.04), but not on Appreciating or Reasoning. No differences by experimental group existed in the decision to join the hypothetical trial for the full sample or higher functioning subsample. Conclusions A decision support tool shows promise for individuals with fragile X syndrome with higher cognitive abilities. Future studies should examine the level of cognitive ability needed for sufficient understanding, whether these findings can be translated to other clinical populations, and the impact of the tool in larger trials and on trial retention.

BACKGROUND: Delays in the diagnosis of children with fragile X syndrome (FXS) suggest the possibility of newborn screening as a way to identify children earlier. However, FXS does not have a proven treatment that must be provided early, and ethical concerns have been raised about the detection of infants who are carriers. This article summarizes major findings from a multisite, prospective, longitudinal pilot screening study. METHODS: Investigators in North Carolina, California, and Illinois collaborated on a study in which voluntary screening for FXS was offered to parents in 3 birthing hospitals. FXS newborn screening was offered to >28 000 families to assess public acceptance and determine whether identification of babies resulted in any measurable harms or adverse events. Secondary goals were to determine the prevalence of FMR1 carrier gene expansions, study the consent process, and describe early development and behavior of identified children. RESULTS: A number of publications have resulted from the project. This article summarizes 10 “lessons learned” about the consent process, reasons for accepting and declining screening, development and evaluation of a decision aid, prevalence of carriers, father participation in consent, family follow-up, and maternal reactions to screening. CONCLUSIONS: The project documented public acceptance of screening as well as the challenges inherent in obtaining consent in the hospital shortly after birth. Collectively, the study provides answers to a number of questions that now set the stage for a next generation of research to determine the benefits of earlier identification for children and families.

Over the past 20 years, research on fragile X syndrome (FXS) has provided foundational understanding of the complex experiences of affected individuals and their families. Despite this intensive focus, there has been little progress on earlier identification, with the average age of diagnosis being 3 years. For intervention and treatment approaches to have the greatest impact, they need to begin shortly after birth. To access this critical timespan, differential methods of earlier identification need to be considered, with an emerging focus on newborn screening practices. Currently, barriers exist that prevent the inclusion of FXS on standard newborn screening panels. To address these barriers, an innovative program is being implemented in North Carolina to offer voluntary screening for FXS under a research protocol, called Early Check. This program addresses the difficulties observed in prior pilot studies, such as recruitment, enrollment, lab testing, and follow-up. Early Check provides an opportunity for stakeholders and the research community to continue to gain valuable information about the feasibility and greater impact of newborn screening on the FXS population.

Background: Challenges in the clinical and research consent process indicate the need to develop tailored, supportive interventions for all individuals, especially those with limited decisional capacity. We developed a tool to enhance shared decision making and the decisional capacity for individuals with fragile X syndrome engaged in the informed consent process for a clinical trial. Objective: We describe the design and development process of a tablet-based decision support tool. Methods: Our development process for the decision support tool employed a user-centered, feature-driven design approach. We began with an environmental scan to catalog relevant mobile apps, and we conducted interviews with people with a diagnosis of fragile X syndrome and clinicians at fragile X syndrome clinics. To develop content for the decision support tool, we extracted key concepts and elements from a real clinical trial consent form and rewrote it using plain-language principles. Results: We used iterative testing to continuously evaluate and revise the decision support tool content. The tool was finalized in 2016 and contained a series of vignettes, quiz questions, and a sorting activity. A randomized controlled trial was then conducted to compare the efficacy of the decision support tool with a standard verbal presentation of material that mimicked typical informed consent practice. Conclusions: The informed consent process is primed to leverage digital health resources that promote increased understanding and engagement of research participants in the consent and research process. The process and experiences we describe may provide a model for other digital health design and development initiatives seeking to create more interactive and accessible decision support resources. Trial Registration: ClinicalTrials.gov NCT02465931; https://www.clinicaltrials.gov/ct2/show/NCT02465931 (Archived by WebCite at http://www.webcitation.org/6zx2KY9YW)

A phase II randomized, placebo-controlled, double-blind study and subsequent open-label extension study evaluated the efficacy, safety, and tolerability of mavoglurant (AFQ056), a selective metabotropic glutamate receptor subtype-5 antagonist, in treating behavioral symptoms in adolescent patients with fragile X syndrome (FXS). A novel method was applied to analyze changes in symptom domains in patients with FXS using the narratives associated with the clinician-rated Clinical Global Impression-Improvement (CGI-I) scale. In the core study, patients were randomized to receive mavoglurant (25, 50, or 100 mg BID) or placebo over 12 weeks. In the extension, patients received 100 mg BID mavoglurant (or the highest tolerated dose) for up to 32 months. Global improvement, as a measure of treatment response, was assessed using the CGI-I scale. Investigators assigning CGI-I scores of 1 (very much improved), 2 (much improved), 6 (much worse), or 7 (very much worse) were provided a standard narrative template to collect further information about the changes observed in patients. Investigator feedback was coded and clustered into categories of improvement or worsening to identify potential areas of improvement with mavoglurant. Treatment effect in each category was characterized using the Cochran–Mantel–Haenszel test. A total of 134 and 103 patients had reached 2 weeks or more of core and extension study treatment, respectively, by the pre-assigned cutoff date for investigator feedback. In the core study, 34 CGI-I scores of 1 or 2 were reported in 28 patients; one patient scored 6. Analysis of the CGI-I narratives did not indicate greater treatment response in patients receiving mavoglurant compared with placebo in any specific improvement domain. There were 54 CGI-I scores of 1 or 2 in 47 patients in the extension study. The most frequently reported categories of improvement were behavior and mood (79.3 and 76.6 % in core and extension studies, respectively), engagement (75.9 and 78.7 %), and communication (69.0 and 61.7 %). A method was established to capture and categorize FXS symptoms using CGI-I narratives. Although this method did not show benefit of drug over placebo, narratives from investigators were mostly based on parental report and thus do not represent a completely objective alternative assessment. The studies described are registered at ClinicalTrials.gov with clinical trial identifier numbers NCT01357239 and NCT01433354 .

Background Emerging evidence suggests that a subset of FMR1 premutation carriers is at an increased risk for cognitive, emotional, and medical conditions. However, because the premutation is rarely diagnosed at birth, the early developmental trajectories of children with a premutation are not known. Methods This exploratory study examined the cognitive, communication, and social-behavioral profiles of 26 infants with a premutation who were identified through participation in a newborn screening for fragile X syndrome pilot study. In this study, families whose newborn screened positive for an FMR1 premutation were invited to participate in a longitudinal study of early development. Twenty-six infants with the premutation and 21 matched, screen-negative comparison babies were assessed using validated standardized measures at 6-month intervals starting as young as 3 months of age. The babies were assessed up to seven times over a 4-year period. Results The premutation group was not statistically different from the comparison group on measures of cognitive development, adaptive behavior, temperament, or overall communication. However, the babies with the premutation had a significantly different developmental trajectory on measures of nonverbal communication and hyperresponsivity to sensory experiences. They also were significantly more hyporesponsive at all ages than the comparison group. Cytosine-guanine-guanine repeat length was linearly associated with overall cognitive development. Conclusions These results suggest that infants with a premutation may present with subtle developmental differences as young as 12 months of age that may be early markers of later anxiety, social deficits, or other challenges thought to be experienced by a subset of carriers.