Alteration of body representation in typical and atypical motor development.

Developmental coordination disorder (DCD) impacts the quality of life and ability to perform coordinated actions in 5% of school-aged children. The quality of body representations of individuals with DCD has been questioned, but never assessed. We hypothesize that children with DCD have imprecise body representations in the sensory and motor domains. Twenty neurotypical children, seventeen children with DCD (8-12 years old) and twenty neurotypical adults (25-45 years old) performed both sensory and motor body representation tasks: a limb identification and a limb movement task. We observed lower accuracy in the sensory task but not in the motor task. In both tasks, we observe a larger amplitude of errors, or synkinesis, in children with DCD than in neurotypical children. In neurotypical children, accuracy was lower than in neurotypical adults in the motor and sensory task, and the amplitude of sensory errors and synkinesis was higher than in neurotypical adults. Using a linear regression model, we showed that sensory accuracy is a good predictor of synkinesis production, and that synkinesis production is a good predictor of sensory accuracy, as can be expected by the perception-action loop. Results support the hypothesis of an imprecision of body representation in DCD. We suggest that this imprecision arises from noise in the body representation used at the level of internal models of action. Future studies may assess whether slower plasticity of body representations, initial imprecision, or both may account for this observation. At the clinical level, prevention strategies targeting body representation in early childhood are strategically important to limit such impairments. RESEARCH HIGHLIGHTS: Body representation is impaired in children with DCD and has a significant cost in terms of the accuracy of sensory identification of body parts and associated movements. Inaccuracies in the body representation measured in perception and in action (error amplitude and synkinesis) are related in both NT children and adults. In typical development, we provide evidence of a strong link between body schema and body image.

Evaluating the impact of virtual reality game training on upper limb motor performance in children and adolescents with developmental coordination disorder: a scoping review using the ICF framework.

OBJECTIVE: This scoping review aims to explore published literature testing Virtual Reality (VR) interventions for improving upper limb motor performance in children and adolescents with Developmental Coordination Disorder (DCD). Our primary focus was on the types of VR systems used and the measurement tools employed within the International Classification of Functioning, Disability and Health Children and Youth Version (ICF-CY) domains in these studies. METHODS: A comprehensive search of six electronic databases up to 11th January 2024 was conducted using predefined terms. Inclusion and exclusion criteria were applied to determine study eligibility, with two authors independently assessing titles, abstracts, and full-text articles. RESULTS: Out of 788 potential studies, 14 met the eligibility criteria. Studies predominantly utilized non-immersive VR (nVR) systems, for example, commercial platforms such as Nintendo Wii. Most interventions targeted general motor coordination or balance, with only four studies specifically focusing on upper limb motor performance. The Movement Assessment Battery for Children-2 was the predominant assessment tool. However, the use of game scores and trial durations raised concerns about the accuracy of assessments. The majority of studies reported no significant improvement in upper limb motor performance following VR interventions, though some noted improvements in specific tasks or overall outcomes. CONCLUSION: The findings suggest that, while nVR interventions are being explored for paediatric motor rehabilitation, their impact on enhancing upper limb motor performance in children with DCD is unclear. The variability in intervention designs, outcome measures, and the predominant focus on general motor skills rather than specific upper limb improvements highlight the need for more targeted research in this area. IMPACT: This review underscores the importance of developing precise and clinically relevant measurement tools in a broader range of VR technologies to optimize the use of VR in therapy for children with DCD. Future research should aim for more rigorous study designs and emerging immersive technologies to maximize therapeutic benefits.

Altered Inferior Parietal Functional Connectivity is Correlated with Praxis and Social Skill Performance in Children with Autism Spectrum Disorder.

Children with autism spectrum disorder (ASD) have difficulties perceiving and producing skilled gestures, or praxis. The inferior parietal lobule (IPL) is crucial to praxis acquisition and expression, yet how IPL connectivity contributes to autism-associated impairments in praxis as well as social-communicative skill remains unclear. Using resting-state functional magnetic resonance imaging, we applied independent component analysis to test how IPL connectivity relates to praxis and social-communicative skills in children with and without ASD. Across all children (with/without ASD), praxis positively correlated with connectivity of left posterior-IPL with the left dorsal premotor cortex and with the bilateral posterior/medial parietal cortex. Praxis also correlated with connectivity of right central-IPL connectivity with the left intraparietal sulcus and medial parietal lobe. Further, in children with ASD, poorer praxis and social-communicative skills both correlated with weaker right central-IPL connectivity with the left cerebellum, posterior cingulate, and right dorsal premotor cortex. Our findings suggest that IPL connectivity is linked to praxis development, that contributions arise bilaterally, and that right IPL connectivity is associated with impaired praxis and social-communicative skills in autism. The findings underscore the potential impact of IPL connectivity and impaired skill acquisition on the development of a range of social-communicative and motor functions during childhood, including autism-associated impairments.

Feasibility and Preliminary Effects of a 1-Week Vestibular Rehabilitation Day Camp in Children with Developmental Coordination Disorder.

AIM: This pilot study investigated the feasibility and preliminary effects of an intensive 1-week day camp program for children with Developmental Coordination Disorder (DCD) that focused on vestibular rehabilitation. METHODS: Ten participants (6-10 years) were assessed twice pre-intervention, post intervention, and at 8-week follow-up. Videonystagmography, Video Head Impulse Tests (vHIT), and Modified Emory Clinical Vestibular Chair Test (m-ECVCT) test were assessed at baseline. Outcomes measures were gaze stability (Dynamic Visual Acuity; DVA), functional gait (Functional Gait Assessment; FGA), balance (Sensory Organization Test), motor function (Bruininks-Oseretsky Test), and participation (Miller Function and Participation). RESULTS: No abnormal results were detected from the videonystagmography, vHIT and m-ECVCT. There was a 100% attendance rate at the camp and assessment sessions. FGA scores significantly improved following intervention and changes were maintained at follow-up. The number of children with abnormal DVA scores decreased from 3 to 1 to 0 between pre-intervention, post-intervention, and follow-up. There were no significant changes in any of the other outcomes following intervention. CONCLUSIONS: Intensive vestibular rehabilitation delivered in a day camp format is feasible and show positive preliminary effects on functional gait and dynamic visual acuity in children with DCD.

Unique deficit in embodied simulation in autism: An fMRI study comparing autism and developmental coordination disorder.

A deficit in pre-cognitively mirroring other people's actions and experiences may be related to the social impairments observed in autism spectrum disorder (ASD). However, it is unclear whether such embodied simulation deficits are unique to ASD or instead are related to motor impairment, which is commonly comorbid with ASD. Here we aim to disentangle how, neurologically, motor impairments contribute to simulation deficits and identify unique neural signatures of ASD. We compare children with ASD (N = 30) to children with Developmental Coordination Disorder (DCD; N = 23) as well as a typically developing group (N = 33) during fMRI tasks in which children observe, imitate, and mentalize about other people's actions. Results indicate a unique neural signature in ASD: during action observation, only the ASD group shows hypoactivity in a region important for simulation (inferior frontal gyrus, pars opercularis, IFGop). However, during a motor production task (imitation), the IFGop is hypoactive for both ASD and DCD groups. For all tasks, we find correlations across groups with motor ability, even after controlling for age, IQ, and social impairment. Conversely, across groups, mentalizing ability is correlated with activity in the dorsomedial prefrontal cortex when controlling for motor ability. These findings help identify the unique neurobiological basis of ASD for aspects of social processing. Furthermore, as no previous fMRI studies correlated brain activity with motor impairment in ASD, these findings help explain prior conflicting reports in these simulation networks.

Novel mRNA-Based Therapy Reduces Toxic Galactose Metabolites and Overcomes Galactose Sensitivity in a Mouse Model of Classic Galactosemia.

Classic galactosemia (CG) is a potentially lethal inborn error of galactose metabolism that results from deleterious mutations in the human galactose-1 phosphate uridylyltransferase (GALT) gene. Previously, we constructed a GalT-/- (GalT-deficient) mouse model that exhibits galactose sensitivity in the newborn mutant pups, reduced fertility in adult females, impaired motor functions, and growth restriction in both sexes. In this study, we tested whether restoration of hepatic GALT activity alone could decrease galactose-1 phosphate (gal-1P) and plasma galactose in the mouse model. The administration of different doses of mouse GalT (mGalT) mRNA resulted in a dose-dependent increase in mGalT protein expression and enzyme activity in the liver of GalT-deficient mice. Single intravenous (i.v.) dose of human GALT (hGALT) mRNA decreased gal-1P in mutant mouse liver and red blood cells (RBCs) within 24 h with low levels maintained for over a week. Repeated i.v. injections increased hepatic GalT expression, nearly normalized gal-1P levels in liver, and decreased gal-1P levels in RBCs and peripheral tissues throughout all doses. Moreover, repeated dosing reduced plasma galactose by 60% or more throughout all four doses. Additionally, a single intraperitoneal dose of hGALT mRNA overcame the galactose sensitivity and promoted the growth in a GalT-/- newborn pup.

The experiences of foundation doctors with dyspraxia: a phenomenological study.

Dyspraxia, otherwise known as Developmental Coordination Disorder (DCD), is a specific learning difficulty (SpLD). Its main difficulties manifest as problems with motor coordination, organisation, academic and social difficulties. There are now more students arriving at university with SpLDs, and, therefore, a similar rise may be expected within medical education. There has been no previous research focusing on dyspraxia in doctors. An interpretive phenomenological approach was used. Six UK foundation schools disseminated the announcements. Three participants took part in loosely structured telephone interviews regarding their experiences of undertaking medical school and foundation school with dyspraxia. These were transcribed verbatim and then thematically analysed. The themes could be split into two main categories: "Weakness and Coping Strategies" and "Perspectives of Dyspraxia". "Weakness" included: clumsiness, organisation and needing extra time. The participants focused on their "Coping Strategies" that included: Ensuring safety, adapted learning preferences and external support. "Perspectives of Dyspraxia" included: diagnosis, career choice, stigma, "normalisation" and the "difference view" or "medical deficit" view of dyspraxia. Doctors with dyspraxia often mask their difficulties through sophisticated coping strategies. These were determined and hardworking individuals who believe that their dyspraxia was a positive aspect of their identity, adopting a "difference view". They felt further education is needed about dyspraxia to change the perceived stigma. There is now a need for further research in this area.

Examining academic confidence and study support needs for university students with dyslexia and/or developmental coordination disorder.

Higher education providers are seeing a shift from externally funded support for students with specific learning difficulties (SpLD), to a need to develop more inclusive practices generally. However, the precise needs of students with different SpLD diagnoses is unknown. A total of 367 students in England and Wales (163 students with dyslexia, 50 students with developmental coordination disorder [DCD/"dyspraxia"], 62 students with dyslexia and DCD, and 92 non-SpLD students) completed an online questionnaire to determine: (a) how confident they are with their study-related capabilities, (b) the types of support they access, and (c) their views on current inclusive practices. Students with dyslexia and students with dyslexia/DCD reported lower confidence in their grades and studying than non-SpLD students, and accessed more technology-related support than students with DCD only. Examination accommodations supporting writing were common for all SpLD students. Inclusive practices were perceived positively, although different priorities were seen across groups. The findings demonstrate the complexities inherent in providing effective support for all students at university, with the varied profiles across and within SpLD groups suggesting that an individualized approach is necessary. Practical implications are discussed.

[Adolescent learning disability: are screening and management helpful?] / Dépistage et prise en charge des troubles de l'apprentissage chez l'adolescent.

Learning disabilities are frequently mentioned in adolescent consultations. But what exactly are they? How is the diagnosis made? What treatment should be offered to the teenager and his or her family to enable them to manage their difficulties as best they can?

Differential Song Deficits after Lentivirus-Mediated Knockdown of FoxP1, FoxP2, or FoxP4 in Area X of Juvenile Zebra Finches.

Mutations in the transcription factors FOXP1 and FOXP2 are associated with speech impairments. FOXP1 is additionally linked to cognitive deficits, as is FOXP4. These FoxP proteins are highly conserved in vertebrates and expressed in comparable brain regions, including the striatum. In male zebra finches, experimental manipulation of FoxP2 in Area X, a striatal song nucleus essential for vocal production learning, affects song development, adult song production, dendritic spine density, and dopamine-regulated synaptic transmission of striatal neurons. We previously showed that, in the majority of Area X neurons FoxP1, FoxP2, and FoxP4 are coexpressed, can dimerize and multimerize with each other and differentially regulate the expression of target genes. These findings raise the possibility that FoxP1, FoxP2, and FoxP4 (FoxP1/2/4) affect neural function differently and in turn vocal learning. To address this directly, we downregulated FoxP1 or FoxP4 in Area X of juvenile zebra finches and compared the resulting song phenotypes with the previously described inaccurate and incomplete song learning after FoxP2 knockdown. We found that experimental downregulation of FoxP1 and FoxP4 led to impaired song learning with partly similar features as those reported for FoxP2 knockdowns. However, there were also specific differences between the groups, leading us to suggest that specific features of the song are differentially impacted by developmental manipulations of FoxP1/2/4 expression in Area X.SIGNIFICANCE STATEMENT We compared the effects of experimentally reduced expression of the transcription factors FoxP1, FoxP2, and FoxP4 in a striatal song nucleus, Area X, on vocal production learning in juvenile male zebra finches. We show, for the first time, that these temporally and spatially precise manipulations of the three FoxPs affect spectral and temporal song features differentially. This is important because it raises the possibility that the different FoxPs control different aspects of vocal learning through combinatorial gene expression or by acting in different microcircuits within Area X. These results are consistent with the deleterious effects of human FOXP1 and FOXP2 mutations on speech and language and add FOXP4 as a possible candidate gene for vocal disorders.

Neocerebellar Crus I Abnormalities Associated with a Speech and Language Disorder Due to a Mutation in FOXP2.

Bilateral volume reduction in the caudate nucleus has been established as a prominent brain abnormality associated with a FOXP2 mutation in affected members of the 'KE family', who present with developmental orofacial and verbal dyspraxia in conjunction with pervasive language deficits. Despite the gene's early and prominent expression in the cerebellum and the evidence for reciprocal cerebellum-basal ganglia connectivity, very little is known about cerebellar abnormalities in affected KE members. Using cerebellum-specific voxel-based morphometry (VBM) and volumetry, we provide converging evidence from subsets of affected KE members scanned at three time points for grey matter (GM) volume reduction bilaterally in neocerebellar lobule VIIa Crus I compared with unaffected members and unrelated controls. We also show that right Crus I volume correlates with left and total caudate nucleus volumes in affected KE members, and that right and total Crus I volumes predict the performance of affected members in non-word repetition and non-verbal orofacial praxis. Crus I also shows bilateral hypo-activation in functional MRI in the affected KE members relative to controls during non-word repetition. The association of Crus I with key aspects of the behavioural phenotype of this FOXP2 point mutation is consistent with recent evidence of cerebellar involvement in complex motor sequencing. For the first time, specific cerebello-basal ganglia loops are implicated in the execution of complex oromotor sequences needed for human speech.

Monoallelic expression of the human FOXP2 speech gene.

The recent descriptions of widespread random monoallelic expression (RMAE) of genes distributed throughout the autosomal genome indicate that there are more genes subject to RMAE on autosomes than the number of genes on the X chromosome where X-inactivation dictates RMAE of X-linked genes. Several of the autosomal genes that undergo RMAE have independently been implicated in human Mendelian disorders. Thus, parsing the relationship between allele-specific expression of these genes and disease is of interest. Mutations in the human forkhead box P2 gene, FOXP2, cause developmental verbal dyspraxia with profound speech and language deficits. Here, we show that the human FOXP2 gene undergoes RMAE. Studying an individual with developmental verbal dyspraxia, we identify a deletion 3 Mb away from the FOXP2 gene, which impacts FOXP2 gene expression in cis. Together these data suggest the intriguing possibility that RMAE impacts the haploinsufficiency phenotypes observed for FOXP2 mutations.

[Update on developemental dyspraxia in children]. / Vignette diagnostique de l'étudiant. Le point sur la dyspraxie développementale chez l'enfant.

After having explained what is dyspraxia, we will briefly talk about narcissistic issues related to school term. Indeed, the defensive tools used by children to deal with learning disabilities are varied and not much specific, which will complicate the medical approach. Then we will describe the symptoms that are specific to search in the history and the first clinic appointment in cases of suspected dyspraxia. Finally, we will give details of how we must consider the exploration and the multidisciplinary taking over of the disorder.

Après avoir réexpliqué ce qu'est la dyspraxie, nous aborderons brièvement les enjeux narcissiques liés à la période scolaire. En effet, les moyens défensifs utilisés par les enfants pour faire face aux difficultés d'apprentissage sont variés et peu spécifiques, ce qui rendra la démarche médicale complexe. Nous décrirons ensuite les symptômes spécifiques à rechercher dans l'anamnèse et le premier entretien clinique en cas de suspicion de dyspraxie. Enfin, nous détaillerons la manière dont il faut envisager le bilan d'exploration et la prise en charge pluridisciplinaire du trouble.

Oculomotor Impairments in Developmental Dyspraxia.

Children with developmental dyspraxia (DD) express impairments in the acquisition of various motor skills and in the development of their social cognition abilities. Although the neural bases of this condition are not fully understood, they are thought to involve frontal cortical areas, subcortical structures, and the cerebellum. Although cerebellar dysfunction is typically difficult to assess and quantify using traditional neurophysiological methods, oculomotor analysis may provide insight into specific cerebellar patterns. The aim of the present study was to investigate, in dyspraxic and typically developing subjects, various oculomotor saccade tasks specifically designed to reveal frontal and cerebellar dysfunction. In addition to evidence supporting prefrontal dysfunction, our results revealed increased variability of saccade accuracy consistent with cerebellar impairments. Furthermore, we found that dyspraxic patients showed decreased velocities of non-visually guided saccades. A closer analysis revealed significant differences in saccade velocity profiles with slightly decreased maximum saccade velocities but markedly prolonged deceleration phases. We show that this pattern was not related to a decreased state of alertness but was suggestive of cerebellar dysfunction. However, the clear predominance of this pattern in non-visually guided saccades warrants alternative hypotheses. In light of previous experimental and anatomical studies, we propose that this unusual pattern may be a consequence of impaired connections between frontal areas and cerebellar oculomotor structures.

Expanding the phenotypic profile of Kleefstra syndrome: A female with low-average intelligence and childhood apraxia of speech.

Kleefstra syndrome (KS) is a rare neurogenetic disorder most commonly caused by deletion in the 9q34.3 chromosomal region and is associated with intellectual disabilities, severe speech delay, and motor planning deficits. To our knowledge, this is the first patient (PQ, a 6-year-old female) with a 9q34.3 deletion who has near normal intelligence, and developmental dyspraxia with childhood apraxia of speech (CAS). At 6, the Wechsler Preschool and Primary Intelligence testing (WPPSI-III) revealed a Verbal IQ of 81 and Performance IQ of 79. The Beery Buktenica Test of Visual Motor Integration, 5th Edition (VMI) indicated severe visual motor deficits: VMI = 51; Visual Perception = 48; Motor Coordination < 45. On the Receptive One Word Picture Vocabulary Test-R (ROWPVT-R), she had standard scores of 96 and 99 in contrast to an Expressive One Word Picture Vocabulary-R (EOWPVT-R) standard scores of 73 and 82, revealing a discrepancy in vocabulary domains on both evaluations. Preschool Language Scale-4 (PLS-4) on PQ's first evaluation reveals a significant difference between auditory comprehension and expressive communication with standard scores of 78 and 57, respectively, further supporting the presence of CAS. This patient's near normal intelligence expands the phenotypic profile as well as the prognosis associated with KS. The identification of CAS in this patient provides a novel explanation for the previously reported speech delay and expressive language disorder. Further research is warranted on the impact of CAS on intelligence and behavioral outcome in KS. Therapeutic and prognostic implications are discussed.

Gait dyspraxia as a clinical marker of cognitive decline in Down syndrome: A review of theory and proposed mechanisms.

Down syndrome (DS) is the most common genetic cause of intellectual disability in children. With aging, DS is associated with an increased risk for Alzheimer's disease (AD). The development of AD neuropathology in individuals with DS can result in further disturbances in cognition and behavior and may significantly exacerbate caregiver burden. Early detection may allow for appropriate preparation by caregivers. Recent literature suggests that declines in gait may serve as an early marker of AD-related cognitive disorders; however, this relationship has not been examined in individuals with DS. The theory regarding gait dyspraxia and cognitive decline in the general population is reviewed, and potential applications to the population with individuals with DS are highlighted. Challenges and benefits in the line of inquiry are discussed. In particular, it appears that gait declines in aging individuals with DS may be associated with known declines in frontoparietal gray matter, development of AD-related pathology, and white matter losses in tracts critical to motor control. These changes are also potentially related to the cognitive and functional changes often observed during the same chronological period as gait declines in adults with DS. Gait declines may be an early marker of cognitive change, related to the development of underlying AD-related pathology, in individuals with DS. Future investigations in this area may provide insight into the clinical changes associated with development of AD pathology in both the population with DS and the general population, enhancing efforts for optimal patient and caregiver support and propelling investigations regarding safety/quality of life interventions and disease-modifying interventions.

Telehealth delivery of Rapid Syllable Transitions (ReST) treatment for childhood apraxia of speech.

BACKGROUND: Rapid Syllable Transitions (ReST) treatment uses pseudo-word targets with varying lexical stress to target simultaneously articulation, prosodic accuracy and coarticulatory transitions in childhood apraxia of speech (CAS). The treatment is efficacious for the acquisition of imitated pseudo-words, and generalization of skill to untreated pseudo-words and real words. Despite the growing popularity of telehealth as a method of service delivery, there is no research into the efficacy of telehealth treatments for CAS. Telehealth service delivery is associated with compromised audio and visual signal transmission that may affect the efficacy of treatment. AIMS: To conduct a phase 1 efficacy study of telehealth delivery of ReST treatment for CAS, and to discuss the efficacy with reference to face-to-face ReST treatment. METHODS & PROCEDURES: Using a multiple baseline across participants design, five children aged 5-11 years with CAS received ReST treatment four times a week for 3 weeks via video conferencing with Adobe Connect. The children's ability to imitate new pseudo-words, generalize the skills to untreated pseudo-words and real word items, and maintain the skills following treatment were assessed. Both visual and statistical analyses were utilized. OUTCOMES & RESULTS: All five children significantly improved with their production of the imitated treated pseudo-word items and significantly generalized to similar untreated pseudo-words and real words. Additionally, two of the children showed significant generalization to imitated phrases with the treatment items. Four of the children maintained their treatment gains up to 4 months post-treatment. Telehealth delivery produced similar acquisition of pseudo-words and generalization to untreated behaviours as face-to-face delivery; however, in the 4 months following treatment, the children showed stable rather than improving speech skills. The intra- and inter-judge reliability was similar in telehealth delivery for face-to-face delivery. Caregivers and clinicians were satisfied with the telehealth treatment. CONCLUSIONS & IMPLICATIONS: This phase 1 study provides promising indications of the efficacy of ReST treatment when delivered four times per week via telehealth, and warrants further large-scale investigation.

Behavioral, Cognitive, and Motor Preparation Deficits in a Visual Cued Spatial Attention Task in Autism Spectrum Disorder.

Abnormalities in motor skills have been regarded as part of the symptomatology characterizing autism spectrum disorder (ASD). It has been estimated that 80 % of subjects with autism display "motor dyspraxia" or clumsiness that are not readily identified in a routine neurological examination. In this study we used behavioral measures, event-related potentials (ERP), and lateralized readiness potential (LRP) to study cognitive and motor preparation deficits contributing to the dyspraxia of autism. A modified Posner cueing task was used to analyze motor preparation abnormalities in children with autism and in typically developing children (N = 30/per group). In this task, subjects engage in preparing motor response based on a visual cue, and then execute a motor movement based on the subsequent imperative stimulus. The experimental conditions, such as the validity of the cue and the spatial location of the target stimuli were manipulated to influence motor response selection, preparation, and execution. Reaction time and accuracy benefited from validly cued targets in both groups, while main effects of target spatial position were more obvious in the autism group. The main ERP findings were prolonged and more negative early frontal potentials in the ASD in incongruent trials in both types of spatial location. The LRP amplitude was larger in incongruent trials and had stronger effect in the children with ASD. These effects were better expressed at the earlier stages of LRP, specifically those related to response selection, and showed difficulties at the cognitive phase of stimulus processing rather that at the motor execution stage. The LRP measures at different stages reflect the chronology of cognitive aspects of movement preparation and are sensitive to manipulations of cue correctness, thus representing very useful biomarker in autism dyspraxia research. Future studies may use more advance and diverse manipulations of movement preparation demands in testing more refined specifics of dyspraxia symptoms to investigate functional connectivity abnormalities underlying motor skills deficits in autism.

Neurodevelopmental attributes of joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type: Update and perspectives.

In the last decade, increasing attention has been devoted to the extra-articular and extra-cutaneous manifestations of joint hypermobility syndrome, also termed Ehlers-Danlos syndrome, hypermobility type (i.e., JHS/EDS-HT). Despite the fact that the current diagnostic criteria for both disorders remain focused on joint hypermobility, musculoskeletal pain and skin changes, medical practice and research have started investigating a wide spectrum of visceral, neurological and developmental complications, which represent major burdens for affected individuals. In particular, children with generalized joint hypermobility often present with various neurodevelopmental issues and can be referred for neurological consultation. It is common that investigations in these patients yield negative or inconsistent results, eventually leading to the exclusion of any structural neurological or muscle disorder. In the context of specialized clinics for connective tissue disorders, a clear relationship between generalized joint hypermobility and a characteristic neurodevelopmental profile affecting coordination is emerging. The clinical features of these patients tend to overlap with those of developmental coordination disorder and can be associated with learning and other disabilities. Physical and psychological consequences of these additional difficulties add to the chief manifestations of the pre-existing connective tissue disorder, affecting the well-being and development of children and their families. In this review, particular attention is devoted to the nature of the link between joint hypermobility, coordination difficulties and neurodevelopmental issues in children. Presumed pathogenesis and management issues are explored in order to attract more attention on this association and nurture future clinical research.

Neuropsychological profiles of patients with 2q37.3 deletion associated with developmental dyspraxia.

Patients with 2q37 deletions manifest brachydactyly mental retardation syndrome (BDMR). Recent advances in human molecular research have revealed that alterations in the histone deacetylase 4 gene (HDAC4) are responsible for the clinical manifestations of BDMR. Here, we report two male patients with 2q37.3 deletions. One of the patients showed a typical BDMR phenotype, and HDAC4 was included in the deletion region. HDAC4 was preserved in the other patient, and he showed a normal intelligence level with the delayed learning of complex motor skills. Detailed neuropsychological examinations revealed similar neuropsychological profiles in these two patients (visuo-spatial dyspraxia) that suggested developmental dyspraxia. These observations suggested that some other candidate genes for neuronal development exist in the telomeric region of HDAC4.