Stacey A Bélanger’s research while affiliated with Université de Montréal and other places

The SET domain containing 2, histone lysine methyltransferase encoded by SETD2 is a dual‐function methyltransferase for histones and microtubules and plays an important role for transcriptional regulation, genomic stability, and cytoskeletal functions. Specifically, SETD2 is associated with trimethylation of histone H3 at lysine 36 (H3K36me3) and methylation of α‐tubulin at lysine 40. Heterozygous loss of function and missense variants have previously been described with Luscan‐Lumish syndrome (LLS), which is characterized by overgrowth, neurodevelopmental features, and absence of overt congenital anomalies. We have identified 15 individuals with de novo variants in codon 1740 of SETD2 whose features differ from those with LLS. Group 1 consists of 12 individuals with heterozygous variant c.5218C>T p.(Arg1740Trp) and Group 2 consists of 3 individuals with heterozygous variant c.5219G>A p.(Arg1740Gln). The phenotype of Group 1 includes microcephaly, profound intellectual disability, congenital anomalies affecting several organ systems, and similar facial features. Individuals in Group 2 had moderate to severe intellectual disability, low normal head circumference, and absence of additional major congenital anomalies. While LLS is likely due to loss of function of SETD2, the clinical features seen in individuals with variants affecting codon 1740 are more severe suggesting an alternative mechanism, such as gain of function, effects on epigenetic regulation, or posttranslational modification of the cytoskeleton. Our report is a prime example of different mutations in the same gene causing diverging phenotypes and the features observed in Group 1 suggest a new clinically recognizable syndrome uniquely associated with the heterozygous variant c.5218C>T p.(Arg1740Trp) in SETD2.

Objective: Primary care practitioners determine access to care for many preschool children with mental health (MH) problems. This study examined rates of mental health (MH) problem identification in preschoolers within primary healthcare settings, related service use, and MH status at follow-up. The findings may inform evidence-based policy and practice development for preschool MH. Method: For this systematic review, MEDLINE®, EMBASE®, PsycInfo®, and ERIC ® were searched from inception to March 7, 2018 for reports in which a screening measure was used to identify MH problems in children aged 24-72 months, seen in primary and community health care settings. Meta-analyses, using random effects models to provide pooled estimates, were used when three or more studies examined identification rates. Findings on service use and persistence of disorders are summarized. Results: Thirty-five publications representing 21 studies met the inclusion criteria. MH problems were identified in 17.6% of preschoolers (95% Confidence Interval (CI): 11.1-24.1), Q = 4.9, p > 0.1 by primary/community healthcare practitioners. Psychiatric diagnoses were identified in 18.4% of preschoolers (95% CI: 12.3 - 24.4), Q= 1.6, p > 0.1. Based on three studies, parents of 67-72% of identified children received advice and 26-42% received specialist referrals. In the subset of studies examining persistence of MH disorders, 25-67% of identified children had MH disorders after one to three years. Conclusion: While the identification rate by primary/community practitioners is similar to the diagnostic rate, these may not consistently be the same children. Substantial variability in management and outcomes indicate need for more rigorous evaluation of primary care services for this population.

Attention-deficit hyperactivity disorder (ADHD) is a chronic neurodevelopmental disorder. Three position statements have been developed by the Canadian Paediatric Society, following systematic literature reviews. Statement objectives are to: • 1) Summarize the current clinical evidence regarding ADHD, • 2) Establish a standard for ADHD care, and • 3) Assist Canadian clinicians in making well-informed, evidence-based decisions to enhance care of children and youth with this condition. Specific topics reviewed in Part 2, which focuses on treatment, include: evidence and context for a range of clinical approaches, combining behavioural and pharmacological interventions to address impairment more effectively, the role of parent and teacher (or other caregiver) training, the use of stimulant and nonstimulant medications, with effects and risks, and dosing and monitoring protocols. Treatment recommendations are based on current guidelines, evidence from the literature, and expert consensus.

Le trouble de déficit de l’attention/hyperactivité (TDAH) est un trouble neurodéveloppemental chronique. La Société canadienne de pédiatrie a préparé trois documents de principes après avoir effectué des analyses bibliographiques systématiques. Leurs objectifs s’établissent comme suit : • 1) Résumer les données probantes cliniques à jour sur le TDAH. • 2) Établir une norme pour les soins du TDAH. • 3) Aider les cliniciens canadiens à prendre des décisions éclairées et fondées sur des données probantes pour rehausser la qualité des soins aux enfants et aux adolescents qui présentent cette affection. Les thèmes abordés dans la partie 1, qui est axée sur le diagnostic, incluent la prévalence, la génétique, la physiopathologie, le diagnostic différentiel, ainsi que les troubles psychiatriques et les troubles du développement comorbides. En plus des recherches dans les bases de données, les auteurs ont analysé les directives les plus récentes de l’American Academy of Pediatrics, de l’American Academy of Child and Adolescent Psychiatry, du National Institute for Health and Clinical Excellence, du Scottish Intercollegiate Guidelines Network et de l’Eunethydis European ADHD Guidelines Group. Puisque le TDAH est un trouble hétérogène, son évaluation médicale complète devrait toujours inclure une anamnèse fouillée, un examen physique et une évaluation approfondie du diagnostic différentiel et des comorbidités connexes. Les auteurs proposent des recommandations précises sur la récolte d’information, les tests à effectuer et les orientations vers divers services.

Attention-deficit hyperactivity disorder (ADHD) is a chronic neurodevelopmental disorder. Three position statements have been developed by the Canadian Paediatric Society, following systematic literature reviews. Statement objectives are to: • 1) Summarize the current clinical evidence regarding ADHD, • 2) Establish a standard for ADHD care, and • 3) Assist Canadian clinicians in making well-informed, evidence-based decisions to enhance care of children and youth with this condition. Specific topics reviewed in Part 1, which focuses on diagnosis, include: prevalence, genetics, pathophysiology, differential diagnosis and comorbid psychiatric disorders and developmental disorders. In addition to database searches, the most recent guidelines of the American Academy of Pediatrics, the American Academy of Child and Adolescent Psychiatry, the National Institute for Health and Clinical Excellence, the Scottish Intercollegiate Guidelines Network, and the Eunethydis European ADHD Guidelines Group, were reviewed. Because ADHD is a heterogeneous disorder, comprehensive medical assessment for ADHD should always include a complete history, a physical examination, and a thorough consideration of differential diagnosis and related comorbidities. Specific recommendations for information gathering, testing, and referral are offered.

Le trouble de déficit de l’attention/hyperactivité (TDAH) est un trouble neurodéveloppemental chronique. La Société canadienne de pédiatrie a préparé trois documents de principes après avoir effectué des analyses bibliographiques systématiques. Leurs objectifs s’établissent comme suit : • 1) Résumer les données probantes cliniques à jour sur le TDAH. • 2) Établir une norme pour les soins du TDAH. • 3) Aider les cliniciens canadiens à prendre des décisions éclairées et fondées sur des données probantes pour rehausser la qualité des soins aux enfants et aux adolescents qui présentent cette affection. La partie 2, axée sur le traitement, porte sur les données probantes et le contexte entourant diverses approches cliniques, la combinaison des interventions comportementales et pharmacologiques pour assurer un traitement plus efficace, le rôle de la formation des parents et des enseignants (ou des autres personnes qui s’occupent de l’enfant), le recours aux stimulants et aux non-stimulants, leurs effets et leurs risques, leur posologie et les protocoles de surveillance. Les recommandations thérapeutiques reposent sur les lignes directrices à jour, les données probantes tirées de publications scientifiques et le consensus d’experts.

Le trouble de déficit de l’attention/hyperactivité (TDAH) est un trouble neurodéveloppemental chronique. La Société canadienne de pédiatrie a préparé trois documents de principes après avoir effectué des analyses bibliographiques systématiques. Leurs objectifs s’établissent comme suit : • 1) Résumer les données probantes cliniques à jour sur le TDAH. • 2) Établir une norme pour les soins du TDAH. • 3) Aider les cliniciens canadiens à prendre des décisions éclairées et fondées sur des données probantes pour rehausser la qualité des soins aux enfants et aux adolescents qui présentent cette affection. Les sujets abordés dans la partie 3, qui porte sur l’association avec le trouble du spectre de l’autisme (TSA), le handicap intellectuel (HI) et la prématurité, incluent les difficultés liées à l’évaluation dia- gnostique, les présentations courantes, le rôle de la génétique et le traitement, y compris les avantages de l’activité physique. Les recommandations reposent sur les lignes directrices à jour, les données probantes tirées des publications scientifiques et le consensus d’experts.

Attention-deficit hyperactivity disorder (ADHD) is a chronic neurodevelopmental disorder. Three position statements have been developed by the Canadian Paediatric Society, following systematic literature reviews. Statement objectives are to: • 1) Summarize the current clinical evidence regarding ADHD, • 2) Establish a standard for ADHD care, and • 3) Assist Canadian clinicians in making well-informed, evidence-based decisions to enhance care of children and youth with this condition. Specific topics reviewed in Part 3, which focuses on associated autism spectrum disorder, intellectual disability, and prematurity, include the challenges of diagnostic assessment, common presentations, the role of genetics, and treatment, including the benefits of physical activity. Recommendations are based on current guidelines, evidence from the literature, and expert consensus.

Global developmental delay (GDD) and intellectual disability (ID) are common concerns in the paediatric setting. Etiologies of both conditions are highly heterogeneous. The American Academy of Pediatrics, the American Academy of Neurology and the British Columbia-based Treatable Intellectual Disability Endeavor (TIDE) protocol have each proposed multitiered investigations of GDD/ID to guide physicians toward an understanding of etiology that optimizes therapeutic yield. This statement provides a framework for the clinical investigation of GDD/ID in children, along with an updated protocol for Canadian physicians to follow in the etiological investigation of GDD/ID. The revised protocol is based on current knowledge and existing guidelines. Key elements of investigation include formal vision and hearing testing, chromosomal microarray, Fragile-X DNA testing and first-tier testing for treatable inborn errors of metabolism. Brain imaging is recommended in the presence of specific neurological findings.

Le retard global du développement (RGD) et le handicap intellectuel (HI) font partie des problèmes courants en milieu pédiatrique. Leur étiologie est très hétérogène. L’American Academy of Pediatrics, l’American Academy of Neurology et le protocole Treatable Intellectual Disability Endeavor (TIDE) de la Colombie-Britannique préconisent des explorations du RGD et du HI en plusieurs étapes, afin d’orienter les médecins vers une recherche étiologique qui optimise le rendement thérapeutique. Le présent document de principes propose un cadre pour l’exploration clinique du RGD et du HI chez les enfants, de même qu’une mise à jour du protocole d’exploration étiologique que peuvent suivre les médecins canadiens. Le protocole révisé repose sur les connaissances à jour et les lignes directrices en place. Les principaux éléments de l’exploration comprennent des tests de la vision et de l’ouïe en bonne et due forme, l’analyse chromosomique sur micropuce, le test d’ADN du gène de l’X fragile et les tests de niveau 1 de dépistage des erreurs innées du métabolisme traitables. En cas de manifestations neurologiques particulières, l’imagerie cérébrale est recommandée.