ABSTRACT
BACKGROUND: Leg stereotypy syndrome (LSS) is a very common, yet underrecognized condition. The pathophysiology of the condition is not well understood. OBJECTIVE: To evaluate and describe the visual kinematic characteristics of the repetitive leg movements in individuals with LSS. METHODS: In this study, we identified and videotaped individuals diagnosed with LSS at the Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine, Houston, Texas between 2000 and 2023. Only patients with LSS and without any co-morbidities were included in the study. Their medical records were carefully reviewed, and the demographic and clinical data were entered into a database. Video recordings of the repetitive leg movements were then analyzed using TremAn software. RESULTS: We identified 14 individuals with LSS who were videotaped at our center. The videos of the 5 cases were too brief and therefore not suitable for TremAn quantitative analysis. The remaining 9 individuals exhibited regular rhythmic oscillations of the legs. Among these, two individuals displayed rhythmic movements only in video segments where their legs were in crossed positions. The other 7 individuals had regular rhythmic oscillations, always with the toes resting on the floor with the heels raised. Frequency analysis showed values between 4.5 and 6.5 Hz, fairly consistent with a variance below 0.5 Hz in individual cases. The oscillation frequency changed from 5.7 Hz to 2.7 Hz while standing. CONCLUSION: In this study, 6 of 9 individuals with LSS showed 4.5-6.5 Hz regular rhythmic leg movements. Studies involving a larger LSS population with additional electrophysiological evaluations are needed to obtain further insights into this common movement disorder.
Subject(s)
Leg , Stereotypic Movement Disorder , Humans , Male , Female , Middle Aged , Aged , Stereotypic Movement Disorder/physiopathology , Stereotypic Movement Disorder/diagnosis , Leg/physiopathology , Video Recording , Biomechanical Phenomena/physiology , AdultABSTRACT
Practitioners need validated strategies for teaching children with significant multiple disabilities (e.g., cognitive, motor, and sensory disability) to use tangible symbols for expressive communication. This single-case experimental design study replicated the positive effect of an adapted protocol for teaching Phase 1 of the Picture Exchange Communication System (PECS) using tangible symbols and extended it to a younger group (4-7 years old) of learners with multiple disabilities. It also tested the effect of an adapted protocol for Phase 2 of PECS to incorporate use of a single switch speech-generating device to gain the attention of an adult communication partner. Two of three students who reached mastery in Phase 1 also reached mastery in Phase 2 and may have generalized requesting behavior from the interventionist (i.e., researchers) to their classroom teacher. Results add to the growing evidence base that shows that the adapted PECS Phase 1 procedures are a promising practice for learners with multiple disabilities, including sensory impairment, and provide preliminary evidence for a more efficient and effective approach to adapting PECS Phase 2 than previously studied for this group of learners. Directions for future research and recommendations for practice are provided.
Subject(s)
Communication Aids for Disabled , Communication Disorders/rehabilitation , Developmental Disabilities/rehabilitation , Speech , Child , Child, Preschool , Communication Disorders/physiopathology , Cytomegalovirus Infections/congenital , Cytomegalovirus Infections/physiopathology , Developmental Disabilities/physiopathology , Female , Hearing Loss/physiopathology , Humans , Hydrocephalus/physiopathology , Lennox Gastaut Syndrome/physiopathology , Male , Stereotypic Movement Disorder/physiopathology , Vision Disorders/physiopathologyABSTRACT
BACKGROUND: Transient neurological symptoms (TNS) are frequent in patients with subdural hematomas (SDH) and many will receive a diagnosis of epilepsy despite a negative workup. OBJECTIVE: To explore if patients with TNS and a negative epilepsy workup (cases) evolved differently than those with a positive EEG (controls), which would suggest the existence of alternative etiologies for TNS. METHODS: We performed a single-center, retrospective, case-control study of patients with TNS post-SDH. The demographics and clinical and semiological features of cases and controls were compared. The outcome and response to antiepileptic drugs were also assessed and a scoring system developed to predict negative EEG. RESULTS: Fifty-nine patients with SDH-associated TNS were included (39 cases and 20 controls). Demographic characteristics were comparable in both groups. Dysphasia and prolonged episodes were associated with a negative EEG. Clonic movements, impaired awareness, positive symptomatology, complete response to antiepileptic drugs, and mortality were associated with a positive EEG. Using semiological variables, we created a scoring system with a 96.6% sensitivity and 100% specificity in predicting case group patients. The differences observed between both groups support the existence of an alternative etiology to seizures in our case group. We propose the term NESIS (NonEpileptic, Stereotypical, and Intermittent Symptoms) to refer to this subgroup and hypothesize that TNS in these patients might result from cortical spreading depolarization. CONCLUSION: We describe NESIS as a syndrome experienced by SDH patients with specific prognostic and therapeutic implications. Independent validation of this new entity is now required.
Subject(s)
Hematoma, Subdural/diagnosis , Hematoma, Subdural/physiopathology , Seizures/diagnosis , Seizures/physiopathology , Stereotypic Movement Disorder/diagnosis , Stereotypic Movement Disorder/physiopathology , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Electroencephalography/methods , Female , Hematoma, Subdural/epidemiology , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Seizures/epidemiology , Stereotypic Movement Disorder/epidemiology , Young AdultABSTRACT
Autism spectrum disorder (ASD) is characterized by the expression of restricted repetitive behaviors (RRBs) and impairments in social recognition and communication. Epidemiological studies demonstrate males are three times more likely than females to be affected. Although this is the case, more recent studies suggest females may be underrepresented in these numbers due to standard clinical measures of RRBs and social behaviors. In addition, many studies examining mouse models of ASD exclude females due to the sex disparity in diagnoses. The present study examined how female and male BTBR Tâ¯+â¯Itpr3tf /J (BTBR) compare to control C57BL/6J mice on tests of RRBs (probabilistic reversal learning, repetitive grooming, spontaneous alternation, and marble burying) and social behaviors (three chambered social approach task). Utilizing a spatial reversal learning test with 80/20 probabilistic feedback, in which ASD individuals have exhibited deficits, we find that female BTBR mice do not show the same impairment found in male BTBR mice. Interestingly, control female C57BL/6J mice required more trials to reach criterion. Female BTBR mice expressed comparable rates of repetitive grooming, marble burying and spontaneous alternation compared to female C57BL/6J mice. Male BTBR mice expressed higher rates of grooming behavior and locomotor activity compared to male C57BL/6J mice, as found in previous studies. Similarly, male BTBR mice showed a reduction in both measures of social approach compared to controls. Both male and female BTBR mice showed a reduction in sniff time for the stranger mouse compared to controls. Together these findings demonstrate how female BTBR mice do not display the RRB profile expressed by male BTBR mice. Testing of repetitive behaviors in ASD needs to better reflect the sex differences in how RRBs manifest in females compared to their extensively researched male counterparts.
Subject(s)
Autism Spectrum Disorder/physiopathology , Sex Factors , Stereotypic Movement Disorder/physiopathology , Animals , Autism Spectrum Disorder/metabolism , Cognition , Disease Models, Animal , Female , Grooming/physiology , Locomotion , Male , Mice , Mice, Inbred C57BL , Motor Activity , Reversal Learning , Social BehaviorABSTRACT
Research examining restricted and repetitive patterns of behavior or interests (RRB) in autism spectrum disorder (ASD) has increased our understanding of its contribution to diagnosis and its role in development. Advances in our knowledge of RRB are hindered by the inconsistencies in how RRB is measured. The present study examined the factor structure of the Repetitive Behavior Scale-Revised (RBS-R) in a sample of 350 children with ASD ages 2-9. Confirmatory factor analysis designed for items with categorical response types was implemented to examine six proposed structural models. The five-factor model demonstrated the most parsimonious fit based on common overall fit indices that was further supported by examination of local model fit indicators, though, the four- and six-factor models evidenced adequate-to-good fit as well. Examination of RRB factor score approaches indicated only minor differences between summed item subscale scores and extracted factor scores with regard to associations with diagnostic measures. All RRB subtypes demonstrated significant associations with cognitive functioning and adaptive behavior. Implications for future research validating the RBS-R as a more extensive clinical measure of RRB in ASD are discussed. Autism Res 2019, 12: 1399-1410. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Repetitive behaviors are one of the two main symptoms of autism spectrum disorder (ASD). To better understand the role of repetitive behaviors, we must establish effective ways of measuring them. This study assessed the measurement qualities of the Repetitive Behavior Scale-Revised (RBS-R) in a sample of 350 children with ASD ages 2-9. We found that the RBS-R measures multiple types of repetitive behaviors and that these behaviors are related to thinking ability and independence.
Subject(s)
Autism Spectrum Disorder/complications , Autism Spectrum Disorder/physiopathology , Psychometrics/methods , Stereotypic Movement Disorder/complications , Stereotypic Movement Disorder/physiopathology , Autism Spectrum Disorder/psychology , Child , Child, Preschool , Factor Analysis, Statistical , Female , Humans , Male , Stereotypic Movement Disorder/psychologyABSTRACT
BACKGROUND: Rett syndrome (RTT) is a severe neurodevelopmental disorder mainly affecting females. One of the main clinical manifestations is hand stereotypies, which is presumed to based on dysfunction rather than on structural impairment. Reflex interictal discharge precipitated by tapping-lips in electroencephalogram (EEG) is a rare phenomenon among RTT. CASE PRESENTATION: We firstly reported a case of RTT concerning interictal reflex discharge precipitated by tapping- lips. The child, female, 5 years old, presented with a significant regression in motor development and language skills. She almost always tapped the lips with the right hand and stopped only when was interrupted. Her EEG results displayed extensive low amplitude fast wave could be elicited by lightly and slowly- rhythm tapping lips and multifocal bilateral discharges could be precipitated by relatively stronger and quicker rhythm action. It was when the movement stopped that corresponding discharges immediately disappeared. Besides, the reflex discharges were not precipitated by tapping- lips using observer's hand at the certain tempo and intensity. The hand stereotypies did not respond to antiepileptic drugs. CONCLUSIONS: Tapping- lips may be a somatosensory stimulation to precipitate interictal discharges in RTT, which may provide another idea to enrich the insight on hand stereotypies of RTT.
Subject(s)
Motor Activity/physiology , Rett Syndrome/physiopathology , Stereotypic Movement Disorder/physiopathology , Child, Preschool , Electroencephalography , Female , Hand , Humans , LipABSTRACT
Children with autism spectrum disorder (ASD) reportedly suffer from sleep problems at a higher rate than typically developing (TD) children. Several previous studies have reported differences in sleep indices (e.g., sleep latency) in children with ASD. However, no previous studies have focused specifically on the time course of body movements. In the present study, we investigated the time course of body movements in young TD children and young children with ASD as well as the relationship between body movements during night and social ability. Seventeen TD children and 17 children with ASD participated in this study (5 to 8 years old). We used an accelerometer attached to the waist to record movements during night and measured the average time course of body movements for 3 nights. Our results demonstrated that the rate of body movement 2 to 3 hours after the onset of body stillness was higher in children with ASD than in TD children. In addition, the higher rate of body movement at 0.5 to 1 hour after the onset of body stillness was associated with a lower social ability in the children with ASD. Our results suggested that the time course of body movements is an objective behavioural index for young children with ASD.
Subject(s)
Accelerometry/methods , Autism Spectrum Disorder/physiopathology , Stereotypic Movement Disorder/physiopathology , Accelerometry/instrumentation , Autism Spectrum Disorder/complications , Autism Spectrum Disorder/diagnosis , Case-Control Studies , Child , Child, Preschool , Female , Humans , Male , Pilot Projects , Sleep/physiology , Stereotypic Movement Disorder/complications , Stereotypic Movement Disorder/diagnosisABSTRACT
AIM: Different neuropsychological dysfunctions have been described in children with primary Stereotypic Movement Disorder (SMD), mainly attention or motor coordination problems. Up to now with no study has evaluated psychomotor functions in preschoolers primary SMD. The aim of this observational study was to gather information on the motor profiles of SMD patients in this age range in comparison with typically developing children. PATIENTS AND METHODS: Twenty-six children (four girls) aged 36 to 76 months (mean= 53 ±10) with primary SMD were assessed by a structured evaluation including the Movement Assessment Battery for Children-Second Edition (MABC-2), the Beery-Buktenica Developmental test of Visual-Motor Integration (VMI), the Repetitive Behaviour Scale-Revised (RBS-R), the Motor Severity Stereotypy Scale (MSSS), and the Child Behaviour Checklist (CBCL). The diagnoses of Intellectual Disability or Autism Spectrum Disorder were exclusion criteria from the study. A comparison group of twenty-seven (four girls) typically developing children without stereotypies aged 36 to 59 months (mean= 48 ±7) was also examined. RESULTS: The MABC-2 total score was lower than 15th percentile in fifteen children with SMD (58%); the worst performances were observed in Balance and Manual Dexterity subtests. The motor coordination score of VMI was lower than 15th percentile in ten children (38%). The majority of the children with low scores at MABC-2 also had low scores at the motor coordination subscale of VMI. MABC-2 standard scores of the clinical group were significantly lower than those of controls on MABC-2 Total, Balance, and Ball Skills subtests. CONCLUSION: The finding of widespread dysfunction of gross and fine motor abilities in preschoolers with primary SMD seems to delineate a peculiar phenotype and could provide new approaches to the management of this neurodevelopment disorder.
Subject(s)
Child Development , Motor Skills/physiology , Stereotypic Movement Disorder/physiopathology , Case-Control Studies , Child Behavior , Child, Preschool , Female , Humans , MaleABSTRACT
Abnormal repetitive behaviors (ARBs) are a prominent symptom of numerous human brain disorders and are commonly seen in rodent models as well. While rodent studies of ARBs continue to dominate the field, mounting evidence suggests that zebrafish (Danio rerio) also display ARB-like phenotypes and may therefore be a novel model organism for ARB research. In addition to clear practical research advantages as a model species, zebrafish share high genetic and physiological homology to humans and rodents, including multiple ARB-related genes and robust behaviors relevant to ARB. Here, we discuss a wide spectrum of stereotypic repetitive behaviors in zebrafish, data on their genetic and pharmacological modulation, and the overall translational relevance of fish ARBs to modeling human brain disorders. Overall, the zebrafish is rapidly emerging as a new promising model to study ARBs and their underlying mechanisms.
Subject(s)
Behavior, Animal/physiology , Cognitive Dysfunction/physiopathology , Disease Models, Animal , Executive Function/physiology , Neurodevelopmental Disorders/physiopathology , Obsessive-Compulsive Disorder/physiopathology , Stereotypic Movement Disorder/physiopathology , Zebrafish/physiology , Animals , Cognitive Dysfunction/genetics , Humans , Neurodevelopmental Disorders/genetics , Obsessive-Compulsive Disorder/genetics , Stereotypic Movement Disorder/geneticsABSTRACT
Autism spectrum disorder (ASD) and Williams syndrome (WS) share psychopathology relating to sensory processing and repetitive behaviors. The relationships between the sensory features and repetitive behaviors in both disorders, and the mechanisms underlying these relationships are not well understood. The aim of this study was to examine the relationships between sensory processing, repetitive behaviors, anxiety, and intolerance of uncertainty in children with ASD and those with WS to better understand the complexity of psychopathology in these disorders. Parents of 19 children with ASD and 16 children with WS, aged between 4 and 9 years, were asked to complete questionnaires assessing their children's sensory experiences, anxiety symptoms, severity and frequency of repetitive behaviors, and level of intolerance of uncertainty. Serial mediation analysis was performed. Direct significant relationships between sensory features and repetitive behaviors were found only for the ASD group. The relationship between sensory processing difficulties and repetitive behaviors was mediated via intolerance of uncertainty in WS. The findings support the value of considering the complexity of the mechanisms underlying the relationship between sensory processing and repetitive behaviors across neurodevelopmental disorders and the mechanisms underlying these aspects of psychopathology in these groups. Understanding these relationships will shed light on some of the most challenging and intractable characteristics of both conditions and inform suitable interventions to improve quality of life for individuals with either ASD or WS. Autism Research 2019, 12: 759-765. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In autism spectrum disorder (ASD) and Williams syndrome (WS) difficulties processing the sensory aspects of the environment, repetitive behaviors and high levels of anxiety co-occur, but the relationships between these features are not well understood. This study found that sensory difficulties were directly associated with repetitive behaviors in children with ASD, but not WS, and in WS this relationship was mediated by intolerance of uncertainty. The findings support the value of considering the complexity of the mechanisms underlying the relationship between sensory processing and repetitive behaviors across neurodevelopmental disorders.
Subject(s)
Anxiety Disorders/physiopathology , Autism Spectrum Disorder/physiopathology , Sensation Disorders/physiopathology , Stereotypic Movement Disorder/physiopathology , Williams Syndrome/physiopathology , Anxiety Disorders/complications , Anxiety Disorders/psychology , Autism Spectrum Disorder/complications , Autism Spectrum Disorder/psychology , Child , Child, Preschool , Female , Humans , Male , Parents , Quality of Life , Sensation Disorders/complications , Sensation Disorders/psychology , Stereotypic Movement Disorder/complications , Stereotypic Movement Disorder/psychology , Surveys and Questionnaires , Uncertainty , Williams Syndrome/complications , Williams Syndrome/psychologyABSTRACT
Tics and stereotypies are the most common pathological repetitive complex motor behaviors occurring during the neurodevelopmental period. Although they may appear transiently during development without acquiring a pathological status, when they become chronic they may be distressing, socially impairing, or even, in the case of malignant tics, potentially physically harmful. Despite a certain similarity in their phenomenology, physicians should be able to distinguish them for their different variability over time, topographical distribution, association with sensory manifestations, and relationship with environmental triggers. The complex phenomenology of tics and stereotypies is constantly enriched by the characterization of novel variants, e.g. tics triggered by auditory stimuli in association with misophonia and stereotypies associated with intense imagery activity. Their pathophysiology remains partially elusive, but both animal model and brain imaging studies confirm the involvement of all the three major loops (sensorimotor, associative and limbic) within the cortico-basal ganglia circuitry. From a management perspective, the greatest advances witnessed in the last decade involve the diffusion of behavioral strategies (e.g. habit reversal training or response interruption and redirection), including the development of protocols for telehealth on online training in order to optimise access. In the context of severe tics, e.g. in refractory Tourette syndrome, there is increasing experience with deep brain stimulation of the intralaminar thalamic nuclei or the globus pallidus internus, although more research is needed to fine tune target choice and stimulation setting definition.
Subject(s)
Autism Spectrum Disorder/physiopathology , Stereotypic Movement Disorder/physiopathology , Tic Disorders/physiopathology , Autism Spectrum Disorder/diagnosis , Autism Spectrum Disorder/therapy , Humans , Stereotypic Movement Disorder/diagnosis , Stereotypic Movement Disorder/therapy , Tic Disorders/diagnosis , Tic Disorders/therapyABSTRACT
One of the core diagnostic features of autism spectrum disorder (ASD) is engagement in stereotypical motor movements, although the etiology of this repetitive behavior is unknown. Since the 1960s, it has been hypothesized that stereotypical motor movements serve a homeostatic regulation function, and thereby a putative coupling mechanism to cardiovascular arousal. However, to date, surprisingly few reports explicitly assess cardio-somatic coupling and stereotypical motor movements. The present exploratory study investigates coupling of stereotypical body rocking and hand flapping to heart rate and heart rate variability (HRV) in a convenience sample (n = 10) of children and young adults with moderate to profound ASD. Motor movements were recorded via video and three-axis accelerometry, and simultaneous electrocardiographic signals were obtained to determine cardiovascular indices at or around the onset of naturalistically occurring stereotypy. Analysis of the heart rate revealed both repetitive body rocking and hand flapping in particular were found to associate with a strikingly similar cardiovascular pattern of acceleration and deceleration unrelated to physical demands associated with the movements themselves. Furthermore, neither type of stereotypical movement provoked directional change in heart rate variability. The implications of these results and opportunities for future research are discussed.
Subject(s)
Autism Spectrum Disorder/physiopathology , Heart Rate/physiology , Motor Activity/physiology , Stereotyped Behavior/physiology , Stereotypic Movement Disorder/physiopathology , Accelerometry , Adolescent , Autism Spectrum Disorder/psychology , Electrocardiography , Female , Hand/physiopathology , Humans , Male , Stereotypic Movement Disorder/psychology , Young AdultABSTRACT
INTRODUCTION: Although focal motor seizures may resemble one or more movement disorders their phenomenology and prevalence remain uncertain. METHODS: To examine the extent to which focal motor seizures can present with a phenomenology fulfilling diagnostic criteria for movement disorders, 100 consecutive patients with focal motor seizures were rated by movement disorders experts, epileptologists, and general neurologists. RESULTS: A focal motor seizure phenomenologically manifested as a defined movement disorder in 29% of the patients from a consecutive video-EEG documented cohort as per consensus among experts: myoclonus and dystonia (10 and 9 cases, respectively) were the most common movement disorders, followed by chorea (4), stereotypies (3) myoclonus-dystonia (2), and tremor (1). CONCLUSIONS: Movement disorders and focal motor epilepsy share overlapping movement phenomenology.
Subject(s)
Chorea/physiopathology , Dystonia/physiopathology , Epilepsy, Partial, Motor/physiopathology , Movement Disorders/physiopathology , Myoclonus/physiopathology , Stereotypic Movement Disorder/physiopathology , Tremor/physiopathology , Adolescent , Adult , Aged , Aged, 80 and over , Chorea/etiology , Cohort Studies , Dystonia/etiology , Electroencephalography , Epilepsy, Partial, Motor/complications , Female , Humans , Male , Middle Aged , Movement Disorders/etiology , Myoclonus/etiology , Stereotypic Movement Disorder/etiology , Tremor/etiology , Young AdultABSTRACT
Pathogenic disruptions to the activity-dependent neuroprotector homeobox (ADNP) gene are among the most common heterozygous genetic mutations associated with autism spectrum disorders (ASDs). Individuals with ADNP disruptions share a constellation of medical and psychiatric features, including ASD, intellectual disability (ID), dysmorphic features, and hypotonia. However, the profile of ASD symptoms associated with ADNP may differ from that of individuals with another ASD-associated single gene disruption or with ASD without a known genetic cause. The current study examined the ASD phenotype in a sample of representative youth with ADNP disruptions. Participants (N = 116, ages 4-22 years) included a cohort with ADNP mutations (n = 11) and three comparison groups with either a mutation to CHD8 (n = 11), a mutation to another ASD-associated gene (other mutation; n = 53), or ASD with no known genetic etiology (idiopathic ASD; n = 41). As expected, individuals with ADNP disruptions had higher rates of ID but less severe social affect symptoms compared to the CHD8 and Idiopathic ASD groups. In addition, verbal intelligence explained more variance in social impairment in the ADNP group compared to CHD8, other mutation, and idiopathic ASD comparison groups. Restricted and repetitive behaviors in the ADNP group were characterized by high levels of stereotyped motor behaviors, whereas the idiopathic ASD group showed high levels of restricted interests. Taken together, these results underscore the role of ADNP in cognitive functioning and suggest that social impairments in ADNP syndrome are consistent with severity of verbal deficits. Autism Res 2018, 11: 1300-1310. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Disruptions to the ADNP gene (i.e., ADNP syndrome) have been associated with autism spectrum disorder (ASD). This article describes intellectual disability, mild social difficulties, and severe repetitive motor movements in a group of 11 youth with ADNP Syndrome. We found lower rates of ASD than previously reported. Verbal skills explained individual variability in social impairment. This pattern suggests that the ADNP gene is primarily associated with learning and memory, and level of social difficulties is consistent with level of verbal impairment.
Subject(s)
Autism Spectrum Disorder/physiopathology , Homeodomain Proteins/genetics , Intellectual Disability/complications , Nerve Tissue Proteins/genetics , Phenotype , Social Communication Disorder/complications , Stereotypic Movement Disorder/complications , Adolescent , Adult , Child , Child, Preschool , Cohort Studies , Female , Humans , Intellectual Disability/genetics , Intellectual Disability/physiopathology , Male , Social Communication Disorder/genetics , Social Communication Disorder/physiopathology , Stereotypic Movement Disorder/genetics , Stereotypic Movement Disorder/physiopathology , Syndrome , Young AdultABSTRACT
The aim of the present study was to assess whether the nature of the main autistic features (i.e., social communication problems and repetitive and restrictive patterns) are better conceptualized as dimensional or categorical in a school population. The study was based on the teacher ratings of two different age groups: 2,585 children between the ages of 10 and 12 (Primary Education; PE) and 2,502 children between the ages of 3 and 5 (Nursery Education; NE) from 60 mainstream schools. The analyses were based on Factor Mixture Analysis, a novel approach that combines dimensional and categorical features and prevents spurious latent classes from appearing. The results provided evidence of the dimensionality of autism spectrum symptoms in a school age population. The distribution of the symptoms was strongly and positively skewed but continuous; and the prevalence of high-risk symptoms for autism spectrum disorders (ASD) and social-pragmatic communication disorder (SCD) was 7.55% of NE children and 8.74% in PE. A categorical separation between SCD and ASD was not supported by our sample. In view of the results, it is necessary to establish clear cut points for detecting and diagnosing autism and to develop specific and reliable tools capable of assessing symptom severity and functional consequences in children with ASD. Autism Res 2018, 11: 979-988. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The results of the present study suggest that the distribution of autism spectrum symptoms are continuous and dimensional among school-aged children and thus support the need to establish clear cut-off points for detecting and diagnosing autism. In our sample, the prevalence of high-risk symptoms for autism spectrum disorders and social-pragmatic communication disorder was around 8%.
Subject(s)
Autism Spectrum Disorder/complications , Autism Spectrum Disorder/physiopathology , Social Communication Disorder/complications , Social Communication Disorder/diagnosis , Stereotypic Movement Disorder/complications , Stereotypic Movement Disorder/diagnosis , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Male , School Teachers , Severity of Illness Index , Social Communication Disorder/physiopathology , Spain , Stereotypic Movement Disorder/physiopathologyABSTRACT
Disrupted-in-schizophrenia 1 (Disc1) is a key molecular driver for the biology of mental diseases. In order to investigate its role in brain function, we previously generated mice lacking exons 2 and 3 of Disc1 on a C57BL/6J genetic background (Disc1Δ2-3/Δ2-3 mice), which have a deficiency of the full-length Disc1 protein. In the present study, we examined the role of Disc1 in cognitive function using a touchscreen-based visual discrimination (VD) task in which mice had to discriminate 1 of 2 stimuli simultaneously displayed on the screen and received a liquid reward. Disc1Δ2-3/Δ2-3 mice showed impaired performance in the VD task, and this was mainly attributed to the perseverative response being significantly stronger than that in wild-type (WT) mice. Furthermore, the numbers of marbles buried in the marble burying test and nestlets shredded in the nestlet shredding test by Disc1Δ2-3/Δ2-3 mice were significantly higher than those by WT mice, suggesting perseverative/compulsive behaviors by Disc1Δ2-3/Δ2-3 mice. A treatment with clozapine ameliorated behavioral deficits in the VD and marble burying tasks. c-Fos expression was significantly stronger in the dorsomedial striatum (DMS), but not the dorsolateral striatum (DLS) after the first VD session in Disc1Δ2-3/Δ2-3 mice than in WT mice. The treatment of mice that had previously expressed hM3Dq in the DMS with clozapine-N-oxide (CNO) impaired performance in the VD task. These results suggest that cognitive impairments accompanied by perseverative/compulsive behaviors in Disc1Δ2-3/Δ2-3 mice are associated with hyperactivity of the DMS.
Subject(s)
Compulsive Behavior/physiopathology , Nerve Tissue Proteins/metabolism , Stereotypic Movement Disorder/physiopathology , Animals , Behavior, Animal/physiology , Clozapine , Cognition , Cognitive Dysfunction/genetics , Disease Models, Animal , Exons , Mice , Mice, Inbred C57BL , Mice, Knockout , Nerve Tissue Proteins/genetics , Photic StimulationABSTRACT
The Xq28 duplication involving the MECP2 gene (MECP2 duplication) has been mainly described in male patients with severe developmental delay (DD) associated with spasticity, stereotypic movements and recurrent infections. Nevertheless, only a few series have been published. We aimed to better describe the phenotype of this condition, with a focus on morphological and neurological features. Through a national collaborative study, we report a large French series of 59 affected males with interstitial MECP2 duplication. Most of the patients (93%) shared similar facial features, which evolved with age (midface hypoplasia, narrow and prominent nasal bridge, thick lower lip, large prominent ears), thick hair, livedo of the limbs, tapered fingers, small feet and vasomotor troubles. Early hypotonia and global DD were constant, with 21% of patients unable to walk. In patients able to stand, lower limbs weakness and spasticity led to a singular standing habitus: flexion of the knees, broad-based stance with pseudo-ataxic gait. Scoliosis was frequent (53%), such as divergent strabismus (76%) and hypermetropia (54%), stereotypic movements (89%), without obvious social withdrawal and decreased pain sensitivity (78%). Most of the patients did not develop expressive language, 35% saying few words. Epilepsy was frequent (59%), with a mean onset around 7.4 years of age, and often (62%) drug-resistant. Other medical issues were frequent: constipation (78%), and recurrent infections (89%), mainly lung. We delineate the clinical phenotype of MECP2 duplication syndrome in a large series of 59 males. Pulmonary hypertension appeared as a cause of early death in these patients, advocating its screening early in life.
Subject(s)
Exotropia/genetics , Hypertension, Pulmonary/genetics , Intellectual Disability/genetics , Mental Retardation, X-Linked/genetics , Methyl-CpG-Binding Protein 2/genetics , Adolescent , Adult , Child , Child, Preschool , Chromosomes, Human, X/genetics , Developmental Disabilities/complications , Developmental Disabilities/genetics , Developmental Disabilities/physiopathology , Epilepsy/complications , Epilepsy/genetics , Epilepsy/physiopathology , Exotropia/complications , Exotropia/physiopathology , France/epidemiology , Humans , Hyperopia/complications , Hyperopia/genetics , Hyperopia/physiopathology , Hypertension, Pulmonary/complications , Hypertension, Pulmonary/physiopathology , Infant , Intellectual Disability/complications , Intellectual Disability/physiopathology , Male , Mental Retardation, X-Linked/complications , Mental Retardation, X-Linked/physiopathology , Pedigree , Phenotype , Somatosensory Disorders/genetics , Somatosensory Disorders/physiopathology , Stereotypic Movement Disorder/complications , Stereotypic Movement Disorder/genetics , Stereotypic Movement Disorder/physiopathology , Young AdultSubject(s)
Catatonia/physiopathology , Echolalia/physiopathology , Stereotyped Behavior/physiology , Stereotypic Movement Disorder/physiopathology , Verbal Behavior/physiology , Animals , Catatonia/complications , Catatonia/diagnosis , Echolalia/etiology , Humans , Stereotypic Movement Disorder/etiology , Stereotypic Movement Disorder/metabolismABSTRACT
BACKGROUND: Catatonia-like presentations in people with autism have been increasingly recognised within research and diagnostic guidelines. The recently developed Attenuated Behaviour Questionnaire has identified that attenuated behaviour [autistic catatonia] is very prevalent in people with autism spectrum disorders (ASDs) and associated with repetitive behaviour. In the current study, we investigated attenuated behaviour within two genetic syndromes associated with ASD and examined ASD and repetitive behaviour as longitudinal predictors of attenuated behaviour. METHOD: The Attenuated Behaviour Questionnaire was completed by parents/carers of 33 individuals with Cornelia de Lange syndrome (CdLS) and 69 with fragile X syndrome (FXS). Information collected from the same informants 4 years previously was utilised to examine ASD and repetitive behaviour as predictors of later attenuated behaviour, controlling for age, gender and ability. RESULTS: Catatonia-like attenuated behaviour was reported for individuals with CdLS (30.3%) and FXS (11.6%). Slowed movement was more prevalent in people with CdLS. No other phenotypic differences were observed. Across the two groups, repetitive behaviour predicted the presence of attenuated behaviour 4 years later, after controlling for age, gender and ability. CONCLUSIONS: Attenuated behaviour can be identified in individuals with CdLS and FXS and may have an effect on both adaptive behaviour and quality of life. Repetitive behaviours predicted subsequent risk within both groups and should be assessed by services as part of a pro-active strategy of support.