Autistic Behavior in Young Boys with Fragile X Syndrome

A sample of 57 boys with fragile X syndrome (fraX) between the ages of 24 and 133 months was rated using the Childhood Autism Rating Scale (CARS) to assess the extent to which autism and autistic features were evident in a young population. Fourteen subjects (approximately 25% of the sample) scored above the cutoff for autism, suggesting a relatively high incidence of autistic behavior. All but 2 of these 14 were in the mildly or moderately autistic range, however, and only a few items received severe ratings, suggesting that severe autism is relatively rare in fraX, at least during the early years. The CARS resulted in a continuum of autistic ratings in the fraX population, but no particular items on the CARS contributed disproportionately to autism ratings. A visual comparison of ratings on an autistic, non-fraX sample revealed similar profiles of ratings, suggesting that differentiating fraX and autism on the basis of CARS ratings is not likely. Within the fraX group, chronological age and socioeconomic status did not correlate with CARS ratings, but severity of delay was strongly related, such that more severely delayed children scored higher (more autistic) on the CARS.     

Adaptive Skills,Behavior Problems,and Parenting Stress in Mothers of Boys With Fragile X Syndrome

The relationship of temperament, atypical behaviors, and adaptive behavior of young boys with Fragile X syndrome on mothers' parenting stress was analyzed. Twenty-six boys with Fragile X syndrome (30–88 months of age) participated. The overall development of the participants was significantly delayed with a specific profile of adaptive behaviors (i.e., strengths in domestic daily living) and behavioral challenges (i.e., high levels of detachment and hypersensitive or hyperactive behavior). Approximately 90% of the mothers reported very high levels of parenting stress. Correlational and regression analyses revealed that temperament and atypical behavior contributed significantly to the level of parenting stress. Implications for early intervention services for families with a child with Fragile X syndrome were discussed.     

Using Discrete Trial Training to Identify Specific Learning Impairments in Boys with Fragile X Syndrome

We examined whether discrete trial training (DTT) could be used to identify learning impairments in mathematical reasoning in boys with fragile X syndrome (FXS). Boys with FXS, aged 10–23 years, and age and IQ-matched controls, were trained to match fractions to pie-charts and pie-charts to decimals either on a computer or with a trained behavior analyst using DTT. Participants with FXS obtained significantly lower learning rates on the fractions to pie-charts task, and were more likely to perseverate on previously reinforced responses during learning compared to controls. These data suggest that DTT can be used to identify specific learning impairments in boys with FXS, as well as other low-functioning individuals with developmental disabilities.     

Language Skills of Males with Fragile X Syndrome or Nonsyndromic Autism Spectrum Disorder

Despite the similarities observed between the fragile X syndrome (FXS) and autism spectrum disorder (ASD) phenotypes, few studies have compared their behavioral profiles outside of ASD symptomatology. In the present study, we sought to compare lexical and grammatical abilities in these two conditions. Comparisons of language abilities in both of these conditions are particularly interesting because both conditions are characterized by difficulties navigating social interactions. Results suggest that although both FXS and ASD are associated with language difficulties, there are important differences between the two conditions in terms of the language profiles observed and the factors influencing language when considering children of similar developmental levels. Theoretical implications are discussed.     

Evidence of a Distinct Behavioral Phenotype in Young Boys With Fragile X Syndrome and Autism

ObjectiveHow does the behavioral expression of autism in fragile X syndrome (FXS + Aut) compare with idiopathic autism (iAut)? Although social impairments and restricted, repetitive behaviors are common to these variants of autism, closer examination of these symptom domains may reveal meaningful similarities and differences. To this end, the specific behaviors comprising the social and repetitive behavioral domains in young children with FXS + Aut and iAut were profiled.MethodTwenty-three male subjects 3 to 5 years old with FXS + Aut were matched by age to a group of 38 boys with iAut. Repetitive behavior was assessed using the Repetitive Behavior Scales-Revised. Social behavior was evaluated using Autism Diagnostic Observation Schedule social item severity scores.ResultsRates of stereotypy, self-injury, and sameness behaviors did not differ between groups, whereas compulsive and ritual behavior scores were significantly lower for subjects with FXS + Aut compared with those with iAut. Those with FXS + Aut scored significantly lower (less severe) than the iAut group on five Autism Diagnostic Observation Schedule measurements of social behavior: gaze integration, quality of social overtures, social smile, facial expressions, and response to joint attention.ConclusionsThe behavioral phenotype of FXS + Aut and iAut are most similar with respect to lower-order (motoric) restricted, repetitive behaviors and social approach, but differ in more complex forms of restricted, repetitive behaviors and some social response behaviors. These findings highlight the phenotypic heterogeneity of autism overall and its unique presentation in an etiologically distinct condition.     

The Fragile X Syndrome

We have begun to appreciate that the extent of this disorder is much wider than merely mental retardation. It is also a common cause of learning and emotional problems in mildly affected female carriers with normal IQs. These children present an enormous challenge to all child-care providers, be they in medicine, education, or in various therapy disciplines. Early identification is essential, and the key to effective management is an innovative and multidisciplinary approach. As disciplines become more familiar with and knowledgeable about this frequently occurring form of mental retardation or cause of learning disabilities, they should become more adept at early identification and early referral for support and intervention.     

Open-Label Memantine in Fragile X Syndrome

Glutamatergic dysfunction is implicated in the pathophysiology of fragile X syndrome (FXS). The purpose of this pilot study was to examine the effectiveness and tolerability of memantine for a number of target symptoms associated with FXS. Medical records describing open-label treatment with memantine in 6 patients with FXS and a comorbid diagnosis of PDD were reviewed. Six patients received memantine over a mean 34.7 weeks of treatment. Four of 6 (67%) patients showed global clinical benefit on ratings with the CGI-I. Symptom specific rating scales, however, showed no statistically significant improvement. Two patient developed treatment-limiting irritability on memantine. Memantine was modestly effective in several patients with FXS. Further systematic study is warranted.     

A Pilot Study of Social Information Processing Skills in Girls With Fragile X Syndrome

Fragile X syndrome (FXS) is a well-described inherited cause of intellectual disability and the most common known genetic cause of autism. Social deficits in girls with FXS are not well understood. To better understand barriers to social functioning that may contribute to mental health outcomes, we administered a theoretically based social information processing (SIP) interview about challenging social situations to 11 verbal mental age-matched girls with and without FXS. We hypothesized that (a) girls with FXS have global SIP impairments and (b) less autism symptomatology is related to better SIP skills in girls with FXS. Compared to controls, girls with FXS performed significantly worse on an early SIP skill (problem identification). Scores on later SIP skills tended to be lower and exhibited moderate to strong effect sizes. Competency in goal generation was correlated with autistic-like communication skills. Systematic studies of SIP skills in larger cohorts of girls with FXS are warranted.     

Social Escape Behaviors in Children with Fragile X Syndrome

Social escape behavior is a common behavioral feature of individuals with fragile X syndrome (fraX). In this observational study, we examined the effect of antecedent social and performance demands on problem behaviors in four conditions: face-to-face interview, silent reading, oral reading and a singing task. Results showed that problem behaviors were significantly more likely to occur during the interview and singing conditions. Higher levels of salivary cortisol were predictive of higher levels of fidgeting behavior and lower levels of eye contact in male participants. There were no associations between level of FMRP expression and social escape behaviors. These data suggest that specific antecedent biological and environmental factors evoke social escape behaviors in fragile X syndrome.     

Epilepsy and EEG Findings in Males with Fragile X Syndrome

PURPOSE AND METHODS: One hundred and ninety-two fragile X male patients were investigated for seizures and EEG findings, 168 in a retrospective and 24 in another prospective study, to characterize the natural history of seizures, epilepsy, and EEG abnormalities in males with this syndrome. RESULTS: Seizures were documented in 35 (18.2%) of 192 patients; they never started before the age of 2 years or after the age of 9 years. Seizures were frequently of the complex partial type and less frequently of the partial motor and generalized type. Seizures involving frontal and temporal lobes were commonly seen and were usually well controlled by anticonvulsants. In the majority of young fragile X patients studied, an age-related paroxysmal EEG pattern was found, which showed neurophysiologic characteristics very similar to those of the centrotemporal spikes. CONCLUSIONS: These findings confirm that fragile X syndrome can be considered a genetic model of epilepsy.     

Autistic Behaviors Among Girls with Fragile X Syndrome

Reports of autistic behaviors were examined for 30 school-age girls with fragile X (fraX) and 31 age- and IQ-matched controls through a structured interview administered to each girl's parent(s). IQ scores were obtained for each participant; anxiety, neuroanatomical, and molecular-genetic data were derived for girls with fraX. Girls with fraX had significantly more autistic behaviors than controls. These behaviors were qualitatively similar to those reported for boys with fraX, but were not correlated with IQ. Anxiety in girls with fraX was positively correlated with abnormal social and communication behaviors; posterior cerebellar vermis area was negatively correlated with measures of communication and stereotypic/restricted behaviors. Severity of stereotypic/restricted behaviors was negatively correlated with the prevalence of active non-fraX chromosomes. Thus anxiety and posterior cerebellar area measures had distinct associations with subsets of autistic behaviors; these associations may have important implications for understanding the neurobiology of autism.     

Emotion Potentiated Startle in Fragile X Syndrome

Social avoidance and anxiety are prevalent in fragile X syndrome (FXS) and are potentially mediated by the amygdala, a brain region critical for social behavior. Unfortunately, functional brain resonance imaging investigation of the amygdala in FXS is limited by the difficulties experienced by intellectually impaired and anxious participants. We investigated the relationship between social avoidance and emotion-potentiated startle, a probe of amygdala activation, in children and adolescents with FXS, developmental disability without FXS (DD), and typical development. Individuals with FXS or DD demonstrated significantly reduced potentiation to fearful faces than a typically developing control group (p < .05). However, among individuals with FXS, social avoidance correlated positively with fearful-face potentiation (p < .05). This suggests that general intellectual disability blunts amygdalar response, but differential amygdala responsiveness to social stimuli contributes to phenotypic variability among individuals with FXS.     

Visual Attention and Autistic Behavior in Infants with Fragile X Syndrome

Aberrant attention is a core feature of fragile X syndrome (FXS), however, little is known regarding the developmental trajectory and underlying physiological processes of attention deficits in FXS. Atypical visual attention is an early emerging and robust indictor of autism in idiopathic (non-FXS) autism. Using a biobehavioral approach with gaze direction and heart activity, we examined visual attention in infants with FXS at 9, 12, and 18?months of age with a cross-sectional comparison to 12-month-old typically developing infants. Analyses revealed lower HR variability, shallower HR decelerations, and prolonged look durations in 12-month old infants with FXS compared to typical controls. Look duration and increased latency to disengage attention were correlated with severity of autistic behavior but not mental age.     

Social Approach and Autistic Behavior in Children with Fragile X Syndrome

Social avoidance is a core phenotypic characteristic of fragile X syndrome (FXS) that has critical cognitive and social consequences. However, no study has examined modulation of multiple social avoidant behaviors in children with FXS. In the current study, we introduce the Social Approach Scale (SAS), an observation scale that includes physical movement, facial expression, and eye contact approach behaviors collected across multiple time points. Our findings suggested that social approach behaviors in children with FXS were affected by age, gender, setting, and time spent with an examiner. Selected social approach behaviors were related to autistic behavior. Increased eye contact over the course of a research assessment, in particular, was found to be a strong predictor of lower autistic behavior.     

Brief Report: Linguistic Mazes and Perseverations in School-Age Boys with Fragile X Syndrome and Autism Spectrum Disorder and Relationships with Maternal Maze Use

Journal of Autism and Developmental Disorders - Autism spectrum disorder (ASD) and fragile X syndrome (FXS) are neurodevelopmental disorders with overlapping pragmatic language impairments. Prior...     

Arousal Modulation in Females with Fragile X or Turner Syndrome

The present study was carried out to examine physiological arousal modulation (heart activity and skin conductance, across baseline and cognitive tasks, in females with fragile X or Turner syndrome and a comparison group of females with neither syndrome. Relative to the comparison group, for whom a greater increase in skin conductance was associated with poor arithmetic performance and less risk taking behavior, females with fragile X displayed a minimal increase in heart activity that was nevertheless associated with poor performance on mental arithmetic. In contrast, no arousal–cognitive performance relationship emerged for the group with Turner syndrome. Taken together, our findings suggest that distinct profiles of arousal modulation might be associated with cognitive deficits in these syndrome populations.     

Emotion Recognition and Visual-Scan Paths in Fragile X Syndrome

This study investigated emotion recognition abilities and visual scanning of emotional faces in 16 Fragile X syndrome (FXS) individuals compared to 16 chronological-age and 16 mental-age matched controls. The relationships between emotion recognition, visual scan-paths and symptoms of social anxiety, schizotypy and autism were also explored. Results indicated that, compared to both control groups, the FXS group displayed specific emotion recognition deficits for angry and neutral (but not happy or fearful) facial expressions. Despite these evident emotion recognition deficits, the visual scanning of emotional faces was found to be at developmentally appropriate levels in the FXS group. Significant relationships were also observed between visual scan-paths, emotion recognition performance and symptomology in the FXS group.