Développement des fonctions exécutives et des théories de l'esprit chez l'enfant ayant une cardiopathie congénitale cyanogène opérée en période néonatale

L objectif général de cette thèse est d explorer le développement des fonctions exécutives (FE) et des théories de l esprit (TdE) chez l enfant ayant une cardiopathie congénitale cyanogène (CCC) et ceci à une période clé dans la construction de ces capacités de haut niveau et dans leurs relations fonctionnelles réciproques. L étude des enfants ayant une CCC et présentant un risque d hypoxie circonscrit à la période néonatale permet d explorer la vulnérabilité précoce des capacités neurocognitives à maturation tardive comme les FE et les TdE. En adoptant une approche longitudinale et transversale, nos objectifs visent à (1) déterminer la trajectoire développementale des FE (inhibition, mémoire de travail et flexibilité cognitive) et spécifier la nature et le degré de leurs dysfonctionnements (2) caractériser le développement des capacités méta-représentationnelles et évaluer le rôle prédictif des différentes composantes exécutives dans les TdE de premier et deuxième ordre, (3) explorer la généralisation des dysfonctionnements aux TdE avec un contenu mental affectif, (4) déterminer les facteurs de risque neurologique néonataux associés aux déficits exécutifs et en TdE, (5) évaluer la contribution des dysfonctionnements exécutifs, des variables médicales et démographiques sur la prévalence de prise en charge de ces enfants. Une cohorte de 45 enfants nés avec une CCC opérés à coeur ouvert en période néonatale et un groupe d enfants sains ont été évalués à un âge moyen de 5 ans (T1) puis ont été à nouveau testés pendant deux années consécutives (T2 et T3). Nos résultats ont mis en évidence un profil de dysfonctionnement hétérogène selon l âge et le domaine cognitif. Ainsi, naitre avec une CCC altère la progression développementale des FE et des TdE avec toutefois une normalisation pour les composantes ayant une émergence plus précoce. Les liens prédictifs observés entre les niveaux initiaux des FE et le développement ultérieur des TdE reflètent des mécanismes de construction typiques mais néanmoins décalés dans le temps. Enfin, le diagnostic prénatal de la CCC, qui a un rôle neuroprotecteur face au risque de cyanose néonatale, est également associé à un meilleur pronostic des FE et des TdE. Ce travail de thèse offre des résultats pionniers dans la compréhension de l impact des vulnérabilités neurologiques néonatales sur la dynamique développementale de fonctions neurocognitives complexes.The general aim of this doctoral dissertation is to explore the development of executive functions (EF) and theory of mind (ToM) in school-aged children with a cyanotic congenital heart disease (CHD) at a key developmental period of progression and functional interactions between these higher order functions . The study of children born with a cyanotic CHD and exposed to a hypoxic risk limited to the neonatal period allows to explore the early vulnerability of late developing neurocognitive functions such as EF and ToM. We used a longitudinal and cross-sectional approach in order to: (1) determine the developmental trajectory of EF (inhibition, working memory and cognitive flexibility) and specify their nature and degree of impairment, (2) characterize the development of meta-representational abilities as well as EFs predictive roles in first- and second-order ToM, (3) evaluate the potential generalization of dysfunction to ToM with an affective component, (4) determine neonatal neurological risk factors associated to EF and ToM impairments, (5) evaluate the impact of executive impairments and medical and demographic variables on the early use of remediation services in these children. A cohort of 45 children born with a cyanotic CHD who underwent neonatal open-heart surgery and a group of comparison children were evaluated at a mean age of 5 years (T1) and then followed-up for two consecutive years (T2 and T3). Our results showed a heterogeneous pattern of dysfunction depending on age and specific domains. Cyanotic CHD affects the dynamics of development for these functions even though the earliest developing abilities tend to normalize. Predictive relations observed between early EF and later ToM suggest typical developmental mechanisms though chronologically delayed. Finally, prenatal diagnosis of the cyanotic CHD, known to play a neuroprotective role for cyanosis management is also associated to a better prognosis for EF and ToM outcomes. This work offers pioneer results on the comprehension of the impact of neonatal neurological vulnerabilities on the developmental dynamics of complex neurocognitive abilities.PARIS5-Bibliotheque electronique (751069902) / SudocSudocFranceF

Consensus-based care recommendations for congenital and childhood-onset myotonic dystrophy type 1

Purpose of reviewMyotonic dystrophy type 1 is a multisystemic disorder caused by a noncoding triplet repeat. The age of onset is variable across the lifespan, but in its most severe form, the symptoms appear at birth (congenital myotonic dystrophy) or in the pediatric age range (childhood-onset myotonic dystrophy). These children have a range of disabilities that reduce the lifespan and cause significant morbidity. Currently, there are no agreed upon recommendations for caring for these children.Recent findingsThe Myotonic Dystrophy Foundation recruited 11 international clinicians who are experienced with congenital and childhood-onset myotonic dystrophy to create consensus-based care recommendations. The experts used a 2-step methodology using elements of the single text procedure and nominal group technique. Completion of this process has led to the development of clinical care recommendations for this population.SummaryChildren with myotonic dystrophy often require monitoring and interventions to improve the lifespan and quality of life. The resulting recommendations are intended to standardize and improve the care of children with myotonic dystrophy

Reading and spelling impairments in children and adolescents with infantile myotonic dystrophy

Abstract This study investigated reading and spelling difficulties in subjects with the juvenile form of myotonic dystrophy (MD). Twenty-three consecutive patients with juvenile MD who were referred to a special clinic were assessed for reading and spelling skills (phonological processing, word identification, narrative comprehension (two tasks), information seeking in a document (TV schedule), and spelling). Reading impairments were frequent (63-84% of the subjects being below the level of literacy depending on the tasks), even in subjects without mental retardation (22-66%) despite normal word identification scores. All but two subjects had spelling difficulties. The severity of these learning difficulties was correlated with longer mutation size and maternal transmission, but could not be related to phonological deficit, suggesting that other brain dysfunction might be involved (e.g., attention, working memory, naming speed, executive function). Children with the juvenile form of MD should systematically be assessed for reading and spelling problems, and correlations with basic cognitive functioning explored.

Psychiatric and cognitive phenotype in children and adolescents with myotonic dystrophy

Myotonic dystrophy type 1 (DM1) is the most frequent inherited neuromuscular disorder. The juvenile form has been associated with cognitive and psychiatric dysfunction, but the phenotype remains unclear. We reviewed the literature to examine the psychiatric phenotype of juvenile DM1 and performed an admixture analysis of the IQ distribution of our own patients, as we hypothesised a bimodal distribution. Two-thirds of the patients had at least one DSM-IV diagnosis, mainly attention deficit/ hyperactivity disorder and anxiety disorder. Two-thirds had learning disabilities comorbid with mental retardation on one hand, but also attention deficit, low cognitive speed and visual spatial impairment on the other. IQ showed a bi-modal distribution and was associated with parental transmission. The psychiatric phenotype in juvenile DM1 is complex. We distinguished two different phenotypic subtypes: one group characterised by mental retardation, severe developmental delay and maternal transmission; and another group characterised by borderline full scale IQ, subnormal development and paternal transmission

Consensus-based care recommendations for adults with myotonic dystrophy type 1

Purpose of review Myotonic dystrophy type 1 (DM1) is a severe, progressive genetic disease that affects between 1 in 3,000 and 8,000 individuals globally. No evidence-based guideline exists to inform the care of these patients, and most do not have access to multidisciplinary care centers staffed by experienced professionals, creating a clinical care deficit. Recent findings The Myotonic Dystrophy Foundation (MDF) recruited 66 international clinicians experienced in DM1 patient care to develop consensus-based care recommendations. MDF created a 2-step methodology for the project using elements of the Single Text Procedure and the Nominal Group Technique. The process generated a 4-page Quick Reference Guide and a comprehensive, 55-page document that provides clinical care recommendations for 19 discrete body systems and/or care considerations. Summary The resulting recommendations are intended to help standardize and elevate care for this patient population and reduce variability in clinical trial and study environments. Described as “one of the more variable diseases found in medicine,” myotonic dystrophy type 1 (DM1) is an autosomal dominant, triplet-repeat expansion disorder that affects somewhere between 1:3,000 and 1:8,000 individuals worldwide.1 There is a modest association between increased repeat expansion and disease severity, as evidenced by the average age of onset and overall morbidity of the condition. An expansion of over 35 repeats typically indicates an unstable and expanding mutation. An expansion of 50 repeats or higher is consistent with a diagnosis of DM1. DM1 is a multisystem and heterogeneous disease characterized by distal weakness, atrophy, and myotonia, as well as symptoms in the heart, brain, gastrointestinal tract, endocrine, and respiratory systems. Symptoms may occur at any age. The severity of the condition varies widely among affected individuals, even among members of the same family. Comprehensive evidence-based guidelines do not currently exist to guide the treatment of DM1 patients. As a result, the international patient community reports varied levels of care and care quality, and difficulty accessing care adequate to manage their symptoms, unless they have access to multidisciplinary neuromuscular clinics. Consensus-based care recommendations can help standardize and improve the quality of care received by DM1 patients and assist clinicians who may not be familiar with the significant variability, range of symptoms, and severity of the disease. Care recommendations can also improve the landscape for clinical trial success by eliminating some of the inconsistencies in patient care to allow more accurate understanding of the benefit of potential therapies

Annoncer une maladie génétique à l'enfant. Désir de savoir, besoin de comprendre

International audienceL’annonce du diagnostic à l’enfant reste un problème complexe sur lequel il n’existe pas de consensus. Lorsqu’il n’y pas de traitement curatif ou préventif, il est difficile pour les parents et pour les médecins de parler avec l’enfant de sa maladie et de son origine génétique. Un des enjeux fondamentaux de l’annonce à l’enfant est de l’accompagner dans sa quête de savoir et dans une mise en sens de ce qui lui arrive. Les questions que l’enfant peut se poser sur sa maladie logent au plus profond de la pulsion épistémologique qui détermine pour beaucoup l’attitude que l’enfant aura face au savoir et aux apprentissages futurs. Son envie de savoir et de comprendre ne devrait pas être étouffée par une volonté de lui épargner quelques supposées souffrances, qu’une parole pourrait, au contraire, libérer. Dans l’annonce à l’enfant, il ne s’agit pas d’informer l’enfant à tout prix, mais de pouvoir établir un dialogue avec lui, rythmé par ses interrogations

Attribution of false belief in French children: Décalages between tasks and cultural differences.

Theory of Mind (ToM) is usually considered a universal cognitive skill that children progressively master in very similar patterns of age-related changes (Wellman, Cross & Watson, 2001). However, developmental trajectories can be modulated by specific experiential factors and differences could exist in the timing of first acquisitions and in the mastering of different components of ToM. Preliminary data suggested that French children, like children in other countries (e.g., China, Japan, Italy; Liu et al, 2008; Lecce & Hughes, 2010), succeed false belief tasks later than English-speaking children as reported in published literature. Moreover, we also found a decalage between performances in Unexpected Content (UC) and Change of Location (CL) FB tasks, the former being succeeded earlier than the latter. The study reported here aimed to check the validity of these preliminary results, controlling more precisely the instructions and the order of presentation of the two tasks. 160 children, 5 to 8 years, were included in this study, with the order of tasks counterbalanced equally among them. The preliminary results were confirmed. Rate of success on the UC FB task correspondedto that obtained with English-speaking children, while success in CL FB task lagged behind. The discussion will bear on the decalage between the tasks and on the significance of these cultural differences

Attribution of false belief in French children: Décalages between tasks and cultural differences.

Theory of Mind (ToM) is usually considered a universal cognitive skill that children progressively master in very similar patterns of age-related changes (Wellman, Cross & Watson, 2001). However, developmental trajectories can be modulated by specific experiential factors and differences could exist in the timing of first acquisitions and in the mastering of different components of ToM. Preliminary data suggested that French children, like children in other countries (e.g., China, Japan, Italy; Liu et al, 2008; Lecce & Hughes, 2010), succeed false belief tasks later than English-speaking children as reported in published literature. Moreover, we also found a decalage between performances in Unexpected Content (UC) and Change of Location (CL) FB tasks, the former being succeeded earlier than the latter. The study reported here aimed to check the validity of these preliminary results, controlling more precisely the instructions and the order of presentation of the two tasks. 160 children, 5 to 8 years, were included in this study, with the order of tasks counterbalanced equally among them. The preliminary results were confirmed. Rate of success on the UC FB task correspondedto that obtained with English-speaking children, while success in CL FB task lagged behind. The discussion will bear on the decalage between the tasks and on the significance of these cultural differences

Use of Early Remedial Services in Children with Transposition of the Great Arteries

International audienceObjectives To characterize the prevalence of use of early remedial services and its associated demographic, medical, and cognitive factors in children aged 4-6 years with corrected transposition of the great arteries (TGA). Study design This was a prospective study of neurocognitive outcomes after TGA. Children underwent formal neu-ropsychological testing including general intelligence and a comprehensive battery of executive functions (EF) including motor and interference control, short-term memory, and working memory as well as cognitive flexibility. Parental reports on the children's behavior and EF were also evaluated. Demographic factors and preoperative, intraoperative, and postoperative factors as well as cognitive factors were examined according to the current use of remediation. Results Forty-five patients (67% male) and their parents participated in this study. Twenty-four (53%) patients were receiving remedial services. Male sex, a postnatal diagnosis of TGA, and a longer postoperative intensive care unit stay were significantly associated with use of remediation. Children receiving remediation had lower EF scores, had more severe EF deficits as observed by formal testing, and were rated as having more behavioral daily life difficulties. However, in the group without remediation, 13 children (43%) also displayed EF deficits rated as moderate to severe. Conclusions Demographic and medical factors could help identify children at higher risk for neurocognitive delays