A complex chromosomal rearrangement involving chromosomes 2, 5, and X in autism spectrum disorder

Here, we describe a female patient with autism spectrum disorder and dysmorphic features that harbors a complex genetic alteration, involving a de novo balanced translocation t(2;X)(q11;q24), a 5q11 segmental trisomy and a maternally inherited isodisomy on chromosome 5. All the possibly damaging genetic effects of such alterations are discussed. In light of recent findings on ASD genetic causes, the hypothesis that all these alterations might be acting in orchestration and contributing to the phenotype is also considered. (C) 2012 Wiley Periodicals, Inc.

A comparison of three therapy methods for children with different types of developmental phonological disorder

Treatment case studies of three children whose speech was characterized by non-developmental errors are described. Three therapy methods were trialed with each child: phonological contrast; core vocabulary and PROMPT. The accuracy and intelligibility of the children's connected speech improved throughout: the course of the programme. Intervention that focused on teaching a rule about the contrastive use of phonemes was most successful for a child who consistently made non-developmental errors. Children making inconsistent errors received most benefit from the core vocabulary approach that markedly enhanced consistency of production. However, once consistency was established, one child benefited from phonological contrast therapy. While the results of the study should be interpreted with caution due to the small sample size and the cumulative effects of intervention, the findings suggest that different parts of a child's phonological and phonetic system may respond to various types of treatment approaches that target different aspects of speech production. The implication drawn is that just as no single treatment approach is appropriate for all children with disordered phonology, management of some children may involve selecting and sequencing a range of different approaches.

Postural control and movement performance during upper limb tasks in children with developmental co-ordination disorder (DCD)

At least 6% of primary school aged children present with DCD, where co-ordination is substantially below the normal range for the child’s age and intelligence. Motor skill difficulties negatively affect academic achievement, recreation and activities of daily living. Poor upper-limb co-ordination is a common difficulty for children with DCD. A possible cause of this problem is deviant muscle timing in proximal muscle groups, which results in poor postural and movement control. While studies have been published investigating postural control in response to external perturbations, detail about postural muscle activity during voluntary movement is limited even in children with normal motor development. No studies have investigated the relationship between muscle timing, resultant arm motion and upper-limb coordination deficits. Objectives: To investigate the relationship between functional difficulties with upper-limb motor skills and neuromuscular components of postural stability and coordination. Specifically, to investigate onset-timing of muscle activity, timing of arm movement, and resultant three-dimensional (3D) arm co-ordination during rapid, voluntary arm movement and to analyse differences arising due to the presence of DCD. This study is part of a larger research program investigating postural stability and control of upper limb movement in children. Design: A controlled, cross-sectional study of differences between children with and without DCD. Methods: This study included 50 children aged eight to 10 years (25 with DCD and 25 without DCD). Children participated in assessment of motor skills according to the Movement ABC Test and a laboratory study of rapid, voluntary arm movements. Parameters investigated included muscle activation timing of shoulder and trunk muscles (surface electromyography), arm movement timing (light sensor) and resultant 3D arm motion (Fastrak). Results: A MANOVA is being used to analyse between-group differences. Preliminary results indicate children with DCD demonstrate altered muscle timing during a rapid arm raise when compared with the control group of children. Conclusion: Differences in proximal muscle timing in children with DCD support the hypothesis that altered proximal muscle activity may contribute to poor proximal stability and consequently poor arm movement control. This has implications for clinical physiotherapy.

Rites of passage: Understanding participation of children with developmental coordination disorder

Children with developmental coordination disorder (DCD) experience difficulty participating in the typical activities of childhood and are known to have a more sedentary pattern of activities than their peers. Little research has been done to investigate the impact of these deficits on the lives of children with DCD and the importance of their participation in the typical activities of childhood. This qualitative study explored the impact of the disorder and the importance of participation for children with DCD from the perspective of the parent. Twelve in-depth interviews were conducted with parents of children with DCD who attended a university clinic specializing in using the Cognitive Orientation to daily Occupational Performance (COOP) approach, a cognitive-based intervention. Findings revealed that incompetence in everyday activities had serious negative effects for the children. Conversely, intervention that was focused on enablement at the activity and participation level had a significant positive impact on the children's quality of life. Emerging themes highlighted the notion that performance competency played an important role in being accepted by peers and being able to be part of the group. As well, parents reported that successful participation built confidence in their children and allowed them to try other new activities. The World Health Organization's International Classification of Functioning, Disability, and Health provides a unique framework for analyzing and understanding the impact of the physical disability on the lives of families with children with DCD. Results illustrate how intervention that focuses on enabling children to choose their own functional goals in the area of physical activity has important implications for enabling participation and building the social networks of children with DCD. (C) 2003 Elsevier B.V. All rights reserved.

Motor and functional skills of children with developmental coordination disorder: A pilot investigation of measurement issues

This paper reports on the motor and functional outcomes of 20 children with developmental coordination disorder (DCD) aged 4-8 years consecutively referred to a pediatric physiotherapy service. Children with a Movement ABC (M-ABC) score less than the 15th percentile, and with no concurrent medical, sensory, physical, intellectual or neurological impairments, were recruited. The Motor Assessment Outcomes Model (MAOM) [Coster and Haley, Infants and Young Children 4 (1992) 11] provided the theoretical base for measurement selection, and preliminary findings at the activities and participation levels of the model are reported in this article. Children with DCD performed at the lower end of the normal range on the Pea-body Developmental Motor Scales (fine motor total score) (M = 85.65, SD = 12.23). Performance on the Visual Motor Integration Test (VMI) standard scores was within the average range (M = 96.15, SD = 10.69). Videotaped observations of the children's writing and cutting indicated that 29% were left-handed and that a large proportion of all children (31%) utilized unusual pencil grasp patterns and immature prehension of scissors. Measurement at the participation level involved use of the Pictorial Scale of Perceived Competence and Social Acceptance (PCSA) and Pediatric Evaluation of Disability Inventory (PEDI). Overall, these young children rated themselves towards the more competent and accepted end of the PCSA over the dimensions of physical and cognitive competence and peer and maternal acceptance. The PEDI revealed generally average performance on social (M = 49.98, SD = 16.62) and mobility function (M = 54.71, SD = 3.99), however, self-care function was below the average range for age (M = 38.01, SD = 12.19). The utility of the MAOM as a framework for comprehensive measurement of functional and motor outcomes of DCD in young children is discussed. (C) 2003 Elsevier B.V. All rights reserved.

Developmental changes in lateralized inhibition of symmetric movements in children with and without Developmental Coordination Disorder.

The present study investigates developmental changes in selective inhibition of symmetric movements with a lateralized switching task from bimanual to unimanual tapping in typically developing (TD) children and with Developmental Coordination Disorder (DCD) from 7 to 10 years old. Twelve right-handed TD children and twelve gender-matched children with DCD and probable DCD produce a motor switching task in which they have (1) to synchronize with the beat of an auditory metronome to produce bimanual symmetrical tapping and (2) to selectively inhibit their left finger's tapping while continuing their right finger's tapping and conversely. We assess (1) the development of the capacity to inhibit the stopping finger (number of supplementary taps after the stopping instruction) and (2) the development of the capacity to maintain the continuing finger (changes in the mean tempo and its variability for the continuing finger's tapping) and (3) the evolution of performance through trials. Results indicate that (1) TD children present an age-related increase in the capacity to inhibit and to maintain the left finger's tapping, (2) DCD exhibits persistent difficulties to inhibit the left finger's tapping, and (3) both groups improve their capacity to inhibit the left finger's movements through trials. In conclusion, the lateralized switching task provides a simple and fine tool to reveal differences in selective inhibition of symmetric movements in TD children and children with DCD. More theoretically, the specific improvement in selective inhibition of the left finger suggests a progressive development of inter-hemispheric communication during typical development that is absent or delayed in children with DCD.

Similarities and dissimilarities between the Movement ABC-2 and the Zurich Neuromotor Assessment in children with suspected developmental coordination disorder.

An established tool for the assessment of motor performance in children with developmental coordination disorder (DCD) is the Movement-ABC-2 (M-ABC-2). The Zurich Neuromotor Assessment (ZNA) is also widely used for the evaluation of children's motor performance, but has not been compared with the M-ABC-2. Fifty-one children (39 males) between 5 and 7 years of age with suspected DCD were assessed using the M-ABC-2 and the ZNA. Rank correlations between scores of different test components were calculated. The structure of the tests was explored using canonical-correlation analysis. The correlation between total scores of the two motor tests was reasonable (0.66; p<0.001). However, ZNA scores were generally lower than those of M-ABC-2, due to poor performance in the fine motor adaptive component and increased contralateral associated movements (CAM). The canonical-correlation analysis revealed that ZNA measures components like pure motor skills and CAM that are not represented in the M-ABC-2. Furthermore, there was also no equivalent for the aiming and catching items of the M-ABC-2 in ZNA. The two tests measure different motor characteristics in children with suspected DCD and, thus, can be used complementary for the diagnosis of the disorder.

Autistic spectrum disorder: evaluating a possible contributing or causal role of epilepsy.

The onset of epilepsy in brain systems involved in social communication and/or recognition of emotions can occasionally be the cause of autistic symptoms or may aggravate preexisting autistic symptoms. Knowing that cognitive and/or behavioral abnormalities can be the presenting and sometimes the only symptom of an epileptic disorder or can even be caused by paroxysmal EEG abnormalities without recognized seizures, the possibility that this may apply to autism has given rise to much debate. Epilepsy and/or epileptic EEG abnormalities are frequently associated with autistic disorders in children but this does not necessarily imply that they are the cause; great caution needs to be exercised before drawing any such conclusions. So far, there is no evidence that typical autism can be attributed to an epileptic disorder, even in those children with a history of regression after normal early development. Nevertheless, there are several early epilepsies (late infantile spasms, partial complex epilepsies, epilepsies with CSWS, early forms of Landau-Kleffner syndrome) and with different etiologies (tuberous sclerosis is an important model of these situations) in which a direct relationship between epilepsy and some features of autism may be suspected. In young children who primarily have language regression (and who may have autistic features) without evident cause, and in whom paroxysmal focal EEG abnormalities are also found, the possible direct role of epilepsy can only be evaluated in longitudinal studies.

Genetic removal of tri-unsaturated fatty acids suppresses developmental and molecular phenotypes of an Arabidopsis tocopherol-deficient mutant. Whole-body mapping of malondialdehyde pools in a complex eukaryote.

Malondialdehyde (MDA) is a small, ubiquitous, and potentially toxic aldehyde that is produced in vivo by lipid oxidation and that is able to affect gene expression. Tocopherol deficiency in the vitamin E2 mutant vte2-1 of Arabidopsis thaliana leads to massive lipid oxidation and MDA accumulation shortly after germination. MDA accumulation correlates with a strong visual phenotype (growth reduction, cotyledon bleaching) and aberrant GST1 (glutathione S-transferase 1) expression. We suppressed MDA accumulation in the vte2-1 background by genetically removing tri-unsaturated fatty acids. The resulting quadruple mutant, fad3-2 fad7-2 fad8 vte2-1, did not display the visual phenotype or the aberrant GST1 expression observed in vte2-1. Moreover, cotyledon bleaching in vte2-1 was chemically phenocopied by treatment of wild-type plants with MDA. These data suggest that products of tri-unsaturated fatty acid oxidation underlie the vte2-1 seedling phenotype, including cellular toxicity and gene regulation properties. Generation of the quadruple mutant facilitated the development of an in situ fluorescence assay based on the formation of adducts of MDA with 2-thiobarbituric acid at 37 degrees C. Specificity was verified by measuring pentafluorophenylhydrazine derivatives of MDA and by liquid chromatography analysis of MDA-2-thiobarbituric acid adducts. Potentially applicable to other organisms, this method allowed the localization of MDA pools throughout the body of Arabidopsis and revealed an undiscovered pool of the compound unlikely to be derived from trienoic fatty acids in the vicinity of the root tip quiescent center.

Mutations in NDUFB11, Encoding a Complex I Component of the Mitochondrial Respiratory Chain, Cause Microphthalmia with Linear Skin Defects Syndrome.

Microphthalmia with linear skin defects (MLS) syndrome is an X-linked male-lethal disorder also known as MIDAS (microphthalmia, dermal aplasia, and sclerocornea). Additional clinical features include neurological and cardiac abnormalities. MLS syndrome is genetically heterogeneous given that heterozygous mutations in HCCS or COX7B have been identified in MLS-affected females. Both genes encode proteins involved in the structure and function of complexes III and IV, which form the terminal segment of the mitochondrial respiratory chain (MRC). However, not all individuals with MLS syndrome carry a mutation in either HCCS or COX7B. The majority of MLS-affected females have severe skewing of X chromosome inactivation, suggesting that mutations in HCCS, COX7B, and other as-yet-unidentified X-linked gene(s) cause selective loss of cells in which the mutated X chromosome is active. By applying whole-exome sequencing and filtering for X-chromosomal variants, we identified a de novo nonsense mutation in NDUFB11 (Xp11.23) in one female individual and a heterozygous 1-bp deletion in a second individual, her asymptomatic mother, and an affected aborted fetus of the subject's mother. NDUFB11 encodes one of 30 poorly characterized supernumerary subunits of NADH:ubiquinone oxidoreductase, known as complex I (cI), the first and largest enzyme of the MRC. By shRNA-mediated NDUFB11 knockdown in HeLa cells, we demonstrate that NDUFB11 is essential for cI assembly and activity as well as cell growth and survival. These results demonstrate that X-linked genetic defects leading to the complete inactivation of complex I, III, or IV underlie MLS syndrome. Our data reveal an unexpected role of cI dysfunction in a developmental phenotype, further underscoring the existence of a group of mitochondrial diseases associated with neurocutaneous manifestations.

An international investigation on the validity of the CSAPPA scale in screening for developmental coordination disorder /

The main objective of the present investigation was to continue the research initiated by Hay and colleagues (2004) in examining the efficacy of the Children's Self-Perceptions of Adequacy in and Predilection for Physical Activity (CSAPPA) scale as a proxy for the short form of the Bruininks-Oseretsky Test of Motor Proficiency (BOTMP-SF) in screening for Developmental Coordination Disorder (DCD) in children. To better appreciate DCD knowledge outside Canada, the measurements of this investigation were expanded in Greece. A translated Greek CSAPP A scale and the BOTMP-SF were administered for the first time in Greek children. A second objective was to investigate the relationship between DCD and various risk factors of coronary artery disease (CAD) in Canadian and Greek children. A sample of 591 (Ms=322; Fs=269) Canadian and 392 (Ms=211; Fs=181) Greek children, aged 9 to 13 years, consented to the BOTMP-SF, CSAPP A Scale, participation in physical activity questionnaire, Leger 20-meter Multistage Shuttle Run test, and body fat using bioelectric impedance. Prevalence of DCD in Canada and Greece was 8% and 19%, respectively. Significant agreement (p

Physical activity of children with developmental coordination disorder in the presence of attention deficit hyperactivity disorder : does gender matter?

Baerg, S., Cairney, J., Hay, J., Rempel, L. and Faught, B.E. (2009). Physical Activity of Children with Developmental Coordination Disorder in the Presence of Attention Deficit Hyperactivity Disorder: Does Gender Matter? Brock University, St. Catharines, Ontario, CANADA. Children with Developmental Coordination Disorder (DCD) have difficulties in motor coordination. Attention-deficit hyperactive disorder (ADHD) is considered the condition most co-morbid with DCD at approximately 50%. Children with DCD are generally less physically active (PA) than their peers, while children with ADHD are often considered more physically active. It is not known if the physical activity patterns of children with DCD-ADHD resemble those of children with primarily DCD or that of their healthy peers. The primary objective of this research was to contrast physical activity patterns between children with DCD, DCD-ADHD, and healthy controls. Since boys are generally reported as more physically active than girls, a secondary objective was to determine if gender moderated the association between groups and physical activity. A sample of males (n=66) and females (n=44) were recruited from the Physical Health Activity Study Team (PHAST) longitudinal study. The Movement Assessment Battery for Children (2nd Ed.) was used to identify probable cases of DCD, and Connor's Revised Parent Rating Scale- Short Version to identify ADHD. Subjects (mean age=12.8±.4 yrs) were allocated to three groups; DCD (n=32), DCD-ADHD (n=30) and control (n=48). Physical activity was monitored for seven days with the Actical® accelerometer (activity count, step count and energy expenditure). Children completed the Participation Questionnaire (PQ) during the in-school session of data collection for the PHAST study. Height, weight and body mass index (BMI) were also determined. Analysis of variance showed significant group differences for activity count (F(2,56)=5.36, p=.007) and PQ (F(2,44 )=6. 71, p=.003) in males, while a significant group difference for step count (F(2,37)=3.55, p=.04) was found in females. Post hoc comparison tests (Tukey) identified significantly lower PQ and activity count between males with OCD and controls (p=.004) and males with DCD-ADHD and controls (p=.003). Conversely, females with DCD-ADHD had significantly more step counts than their controls (p=.01). Analysis of covariance demonstrated a gender by DCD groups negative interaction for males (activity count) (F(2,92):;:3.11, p=.049) and a positive interaction for females (step count) (F(1,92)=4.92, p=.009). Hyperactivity in females with DCD-ADHD appears to contribute to more physical activity, whereas DCD may contribute to decreased activity in males with DCD and DCDADHD. Further research is needed to examine gender differences in physical activity within the context of DCD and ADHD.

The role of physical activity and perceived adequacy on cardiorespiratory fitness in children with developmental coordination disorder

Evidence suggests that children with developmental coordination disorder (DCD) have lower levels of cardiorespiratory fitness (CRF) compared to children without the condition. However, these studies were restricted to field-based methods in order to predict V02 peak in the determination of CRF. Such field tests have been criticised for their ability to provide a valid prediction of V02 peak and vulnerability to psychological aspects in children with DCD, such as low perceived adequacy toward physical activity. Moreover, the contribution of physical activity to the variance in V02 peak between the two groups is unknown. The purpose of our study was to determine the mediating role of physical activity and perceived adequacy towards physical activity on V02 peak in children with significant motor impairments. This prospective case-control design involved 122 (age 12-13 years) children with significant motor impairments (n=61) and healthy matched controls (n=61) based on age, gender and school location. Participants had been previously assessed for motor proficiency and classified as a probable DCD (p-DCD) or healthy control using the movement ABC test. V02 peak was measured by a progressive exercise test on a cycle ergometer. Perceived adequacy was measured using a 7 -item subscale from Children's Selfperception of Adequacy and Predilection for Physical Activity scale. Physical activity was monitored for seven days with the Actical® accelerometer. Children with p-DCD had significantly lower V02 peak (48.76±7.2 ml/ffm/min; p:50.05) compared to controls (53.12±8.2 ml/ffm/min), even after correcting for fat free mass. Regression analysis demonstrated that perceived adequacy and physical activity were significant mediators in the relationship between p-DCD and V02 peak. In conclusion, using a stringent laboratory assessment, the results of the current study verify the findings of earlier studies, adding low CRF to the list of health consequences associated with DCD. It seems that when testing for CRF in this population, there is a need to consider the psychological barriers associated with their condition. Moreover, strategies to increase physical activity in children with DCD may result in improvement in their CRF.