Medical Specialties Commons^™

Eight Years After An International Workshop On Myotonic Dystrophy Patient Registries: Case Study Of A Global Collaboration For A Rare Disease., Libby Wood, Guillaume Bassez, Corinne Bleyenheuft, Craig Campbell, Louise Cossette, Aura Cecilia Jimenez-Moreno, Yi Dai, Hugh Dawkins, Jorge Alberto Diaz Manera, Celine Dogan, Rasha El Sherif, Barbara Fossati, Caroline Graham, James Hilbert, Kristinia Kastreva, En Kimura, Lawrence Korngut, Anna Kostera-Pruszczyk, Christopher Lindberg, Bjorn Lindvall, Elizabeth Luebbe, Anna Lusakowska, Radim Mazanec, Giovani Meola, Liannna Orlando, Masanori P Takahashi, Stojan Peric, Jack Puymirat, Vidosava Rakocevic-Stojanovic, Miriam Rodrigues, Richard Roxburgh, Benedikt Schoser, Sonia Segovia, Andriy Shatillo, Simone Thiele, Ivailo Tournev, Baziel Van Engelen, Stanislav Vohanka, Hanns Lochmüller

Paediatrics Publications

Background

Myotonic Dystrophy is the most common form of muscular dystrophy in adults, affecting an estimated 10 per 100,000 people. It is a multisystemic disorder affecting multiple generations with increasing severity. There are currently no licenced therapies to reverse, slow down or cure its symptoms. In 2009 TREAT-NMD (a global alliance with the mission of improving trial readiness for neuromuscular diseases) and the Marigold Foundation held a workshop of key opinion leaders to agree a minimal dataset for patient registries in myotonic dystrophy. Eight years after this workshop, we surveyed 22 registries collecting information on myotonic dystrophy patients to assess …

A Qualitative Examination Of Women's Self-Presentation And Social Physique Anxiety During Injury Rehabilitation, Molly V. Driediger, Craig R. Hall, Carly D. Mckay

Paediatrics Publications

No abstract provided.

App21 Transgenic Rats Develop Age-Dependent Cognitive Impairment And Microglia Accumulation Within White Matter Tracts., Nina Weishaupt, Qingfan Liu, Sheojung Shin, Ramandeep Singh, Yuksel Agca, Cansu Agca, Vladimir Hachinski, Shawn Narain Whitehead

Paediatrics Publications

Background

Most of the animal models commonly used for preclinical research into Alzheimer's disease (AD) largely fail to address the pathophysiology, including the impact of known risk factors, of the widely diagnosed sporadic form of the disease. Here, we use a transgenic rat (APP21) that does not develop AD-like pathology spontaneously with age, but does develop pathology following vascular stress. To further the potential of this novel rat model as a much-needed pre-clinical animal model of sporadic AD, we characterize APP21 transgenic rats behaviorally and histologically up to 19 months of age.

Methods

The open field test was used as …

Low Agreement Between Modified-Schwartz And Ckd-Epi Egfr In Young Adults: A Retrospective Longitudinal Cohort Study., Michael Webster-Clark, Byron Jaeger, Yi Zhong, Guido Filler, Ana Alvarez-Elias, Nora Franceschini, Maria E Díaz-González De Ferris

Paediatrics Publications

Background

While there is a great deal of research updating methods for estimating renal function, many of these methods are being developed in either adults with CKD or younger children. Currently, there is limited understanding of the agreement between the modified new bedside Schwartz estimated glomerular filtration rate (eGFR) formula and the adult CKD-EPI formula in adolescents and young adults (AYAs) with chronic kidney disease (CKD) measured longitudinally.

Methods

Longitudinal cohort study of 242 patients (10-30 years) with CKD, followed retrospectively in a single tertiary centre as they transitioned from the paediatric- to adult-focused settings. The study population came from …

Magnetic Resonance Imaging In The Diagnosis Of White Matter Signal Abnormalities., Ravi Datar, Asuri Narayan Prasad, Keng Yeow Tay, Charles Anthony Rupar, Pavlo Ohorodnyk, Michael Miller, Chitra Prasad

Paediatrics Publications

Background White matter abnormalities (WMAs) pose a diagnostic challenge when trying to establish etiologic diagnoses. During childhood and adult years, genetic disorders, metabolic disorders and acquired conditions are included in differential diagnoses. To assist clinicians and radiologists, a structured algorithm using cranial magnetic resonance imaging (MRI) has been recommended to aid in establishing working diagnoses that facilitate appropriate biochemical and genetic investigations. This retrospective pilot study investigated the validity and diagnostic utility of this algorithm when applied to white matter signal abnormalities (WMSAs) reported on imaging studies of patients seen in our clinics. Methods The MRI algorithm was applied to …

Physical Activity Self-Management Interventions For Adults With Spinal Cord Injury: Part 2 – Exploring The Generalizability Of Findings From Research To Practice, Shauna M. Burke, Jennifer R. Tomasone, Natalie V. Scime, Jasmin K. Ma, Samantha M. Harden, Dalton L. Wolfe

Paediatrics Publications

Despite the benefits associated with regular participation in physical activity, individuals with spinal cord injury (SCI) remain insufficiently active. The ability to self-manage participation may increase physical activity levels, but only if self-management interventions can be implemented in the ‘real world’. The purpose of this review was to examine the degree to which authors of published studies of LTPA self-management interventions for individuals with SCI have reported on factors that could increase the likelihood of translating this research into practice. A systematic search of five databases was conducted, yielding 33 eligible studies representing 31 interventions. Each intervention was assessed using …

Physical Activity Self-Management Interventions For Adults With Spinal Cord Injury: Part 1–A Systematic Review Of The Use And Effectiveness Of Behavior Change Techniques, Jennifer R. Tomasone, Stephanie M. Flood, Jasmin K. Ma, Natalie V. Scime, Shauna M. Burke, Lindsay Sleeth, Stephanie Marrocco

Paediatrics Publications

Objectives: To determine which behavior change techniques (BCTs) have been used within leisure time physical activity (LTPA) self-management interventions for persons with spinal cord injury (SCI), and which BCTs were effective for improving LTPA behavior and/or its antecedents. Design: Systematic review informed by the PRISMA guidelines. Methods: A comprehensive literature search was conducted using five databases. Study characteristics were extracted from included articles and intervention descriptions were coded using the BCT Taxonomy V.1. Effectiveness and maintenance of BCTs as well as the level of behavior change theory use in the design of interventions were examined within experimental studies. Results: Thirty-one …

Non-Canonical Functions Of The Rb Protein In Cancer, Frederick A. Dick, David W. Goodrich, Julien Sage, Nicholas J. Dyson

Paediatrics Publications

The canonical model of RB-mediated tumour suppression developed over the past 30 years is based on the regulation of E2F transcription factors to restrict cell cycle progression. Several additional functions have been proposed for RB, on the basis of which a non-canonical RB pathway can be described. Mechanistically, the non-canonical RB pathway promotes histone modification and regulates chromosome structure in a manner distinct from cell cycle regulation. These functions have implications for chemotherapy response and resistance to targeted anticancer agents. This Opinion offers a framework to guide future studies of RB in basic and clinical research.

Encouraging Kids To Hop, Skip, And Jump: Emphasizing The Need For Higher-Intensity Physical Activity In Childcare, Molly Driediger, Leigh M. Vanderloo, Stephanie Truelove, Brianne A. Bruijns, Patricia Tucker

Paediatrics Publications

No abstract provided.

Methadone For Analgesia In Children With Life-Limiting Illness: Experience From A Tertiary Children's Health Service., Christine Mott, Amrita Sarpal, Krista Moss, Anthony Herbert

Paediatrics Publications

Methadone has the potential to assist in the management of pain in children with life-limiting illness, but its use is limited by its complex pharmacokinetic profile and limited research on its use in children. This is a retrospective review of the use of methadone as an analgesic in 16 children with life-limiting illness. Efficacy, dosing and side effect profile were analysed. Fifteen (94%) patients had improvements in their analgesia with minimal observed adverse effects. Patients were either rapidly converted from a prior opioid in one change or received methadone as an adjunct medication. Conversions were calculated using ratios frequently in …

Inactivation Of Hepatic Atrx In Atrx Foxg1cre Mice Prevents Reversal Of Aging‐Like Phenotypes By Thyroxine, Megan E Rowland, Yan Jiang, Frank Beier, Nathalie G Bérubé

Paediatrics Publications

ATRX is an ATP‐dependent chromatin remodeler required for the maintenance of genomic integrity. We previously reported that conditional Atrx ablation in the mouse embryonic forebrain and anterior pituitary using the Foxg1cre driver causes reduced health and lifespan. In these mice, premature aging‐like phenotypes were accompanied by low circulating levels of insulin‐like growth factor 1 (IGF‐1) and thyroxine (T4), hormones that maintain stem cell pools and normal metabolic profiles, respectively. Based on emerging evidence that T4 stimulates expression of IGF‐1 in pre‐pubertal mice, we tested whether T4 supplementation in Atrx Foxg1cre mice could restore IGF‐1 levels and ameliorate premature aging‐like phenotypes. …

Measuring Performance On The Healthcare Access And Quality Index For 195 Countries And Territories And Selected Subnational Locations: A Systematic Analysis From The Global Burden Of Disease Study 2016, Gbd 2016 Healthcare Access And Quality Collaborators

Paediatrics Publications

BACKGROUND: A key component of achieving universal health coverage is ensuring that all populations have access to quality health care. Examining where gains have occurred or progress has faltered across and within countries is crucial to guiding decisions and strategies for future improvement. We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) to assess personal health-care access and quality with the Healthcare Access and Quality (HAQ) Index for 195 countries and territories, as well as subnational locations in seven countries, from 1990 to 2016.

METHODS: Drawing from established methods and updated estimates from GBD …

Chronic Kidney Disease Stage Affects Small, Dense Low-Density Lipoprotein But Not Glycated Low-Density Lipoprotein In Younger Chronic Kidney Disease Patients: A Cross-Sectional Study., Guido Filler, Sepideh Taheri, Christopher Mcintyre, Connor Smith, Lakshmimathy Subramanian, Gerhard Fusch, Christoph Fusch

Paediatrics Publications

Background

Small, dense low-density lipoprotein (sd-LDL) and glycated LDL (g-LDL) have been associated with cardiovascular disease (CVD) in chronic kidney disease (CKD) in patients >60 years of age. Since young adult and paediatric patients have shorter exposure to Framingham-type risk factors, our study aims to determine whether younger CKD patients exhibit the same sd-LDL and g-LDL pattern.

Methods

After ethics board approval, this cross-sectional study was conducted at two universities with 44 patients (mean ± standard deviation age 12.6 ± 4.9, range 2-24 years) with CKD stage of 1-5. Laboratory parameters studied were Cystatin C (CysC), CysC estimated glomerular filtration …

Evaluation Of Primary Caregivers' Perceptions On Home Trampoline Use, Supriya Singh, Kamary Coriolano, Jacob Davidson, Megan Cashin, Timothy Carey, Debra Bartley

Paediatrics Publications

Trampolines are widely used by children, but trampoline injuries can be severe and may require hospital care or even surgery. This pilot study examined the effectiveness of an educational intervention on caregivers' perceptions of trampoline use and safety for their children. Primary caregivers were recruited from the orthopedic clinic at the Children's Hospital at our institution in 2015. Caregivers were asked to complete a survey at two time points, initially in clinic and one week post educational intervention. The educational intervention was a pamphlet outlining trampoline safety data. Data analysis occurred in 2016. From the 100 primary caregivers recruited, 39 …

Stable Expression Of Α1-Antitrypsin Portland In Mda-Mb-231 Cells Increased Mt1-Mmp And Mmp-9 Levels, But Reduced Tumour Progression., J.A. Wilson, C.A. Muir, C. L. Evered, M. A. Cepeda, S. Damjanovski

Paediatrics Publications

The membrane bound matrix metalloproteinase MT1-MMP plays roles in modulating cell movement, independent of its abilities to remodel the extracellular matrix. Unlike many MMPs, MT1-MMP is activated in the Golgi prior to secretion by a pro-protein convertase, primarily furin. Regulation of the activation of pro-MT1-MMP has been methodically investigated, as altering the level of the active protein has broad implications in both activating other proMMPs, including pro-MMP-2, and many subsequent remodelling events. Our previous work in MCF-7 cells has demonstrated that modest, and not extremely high, levels of active MT1-MMP manifests into altered cell morphology and movement. At this low …

Hiv-1 Tat Expression And Sulphamethoxazole Hydroxylamine Mediated Oxidative Stress Alter The Disulfide Proteome In Jurkat T Cells, Kemi Adeyanju, John R. Bend, Michael J. Rieder, Gregory A. Dekaban

Paediatrics Publications

Background

Adverse drug reactions (ADRs) are a significant problem for HIV patients, with the risk of developing ADRs increasing as the infection progresses to AIDS. However, the pathophysiology underlying ADRs remains unknown. Sulphamethoxazole (SMX) via its active metabolite SMX-hydroxlyamine, when used prophylactically for pneumocystis pneumonia in HIV-positive individuals, is responsible for a high incidence of ADRs. We previously demonstrated that the HIV infection and, more specifically, that the HIV-1 Tat protein can exacerbate SMX-HA-mediated ADRs. In the current study, Jurkat T cell lines expressing Tat and its deletion mutants were used to determine the effect of Tat on the thiol …

Genomic Dna Methylation-Derived Algorithm Enables Accurate Detection Of Malignant Prostate Tissues, Erfan Aref-Eshghi, Laila C Schenkel, Peter Ainsworth, Hanxin Lin, David I Rodenhiser, Jean-Claude Cutz, Bekim Sadikovic

Paediatrics Publications

Introduction

The current methodology involving diagnosis of prostate cancer (PCa) relies on the pathology examination of prostate needle biopsies, a method with high false negative rates partly due to temporospatial, molecular, and morphological heterogeneity of prostate adenocarcinoma. It is postulated that molecular markers have a potential to assign diagnosis to a considerable portion of undetected prostate tumors. This study examines the genome-wide DNA methylation changes in PCa in search of genomic markers for the development of a diagnostic algorithm for PCa screening.

Methods

Archival PCa and normal tissues were assessed using genomic DNA methylation arrays. Differentially methylated sites and regions …

An International Delphi Survey For The Definition Of The Variables For The Development Of New Classification Criteria For Periodic Fever Aphtous Stomatitis Pharingitis Cervical Adenitis (Pfapa)., Federica Vanoni, Silvia Federici, Jordi Antón, Karyl S Barron, Paul Brogan, Fabrizio De Benedetti, Fatma Dedeoglu, Erkan Demirkaya, Veronique Hentgen, Tilmann Kallinich, Ronald Laxer, Ricardo Russo, Natasa Toplak, Yosef Uziel, Alberto Martini, Nicolino Ruperto, Marco Gattorno, Michael Hofer

Paediatrics Publications

Background

Diagnosis of Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) is currently based on a set of criteria proposed in 1999 modified from Marshall's criteria. Nevertheless no validated evidence based set of classification criteria for PFAPA has been established so far. The aim of this study was to identify candidate classification criteria PFAPA syndrome using international consensus formation through a Delphi questionnaire survey.

Methods

A first open-ended questionnaire was sent to adult and pediatric clinicians/researchers, asking to identify the variables thought most likely to be helpful and relevant for the diagnosis of PFAPA. In a second survey, respondents …

Medical Decision-Making In Paediatrics: Infancy To Adolescence, Kevin W. Coughlin

Paediatrics Publications

Medical decision-making in the paediatric population is complicated by the wide variation in physical and psychological development that occurs as children progress from infancy to adolescence. Parents and legal guardians are the de facto decision-makers in early infancy, but thereafter, the roles of parents/ legal guardians and paediatric patients become ever more complex. Health care providers (HCPs), while not decision-makers per se, have a significant role in medical decision-making throughout childhood. This statement outlines the ethical principles of medical decision-making for HCPs involved in caring for paediatric patients. This revision focuses on individual decision-making in the context of the patient–provider …

Does Specialist Physician Supply Affect Pediatric Asthma Health Outcomes?, Guido Filler, Tom Kovesi, Erik Bourdon, Sarah Ann Jones, Laurentiu Givelichian, Cheryl Rockman-Greenberg, Jason Gilliland, Marion Williams, Elaine Orrbine, Bruno Piedboeuf

Paediatrics Publications

Background

Pediatrician and pediatric subspecialist density varies substantially among the various Canadian provinces, as well as among various states in the US. It is unknown whether this variability impacts health outcomes. To study this knowledge gap, we evaluated pediatric asthma admission rates within the 2 Canadian provinces of Manitoba and Saskatchewan, which have similarly sized pediatric populations and substantially different physician densities.

Methods

This was a retrospective cross-sectional cohort study. Health regions defined by the provincial governments, have, in turn, been classified into "peer groups" by Statistics Canada, on the basis of common socio-economic characteristics and socio-demographic determinants of health. …

Treating Pediatric Neuromuscular Disorders: The Future Is Now, James J Dowling, Hernan D Gonorazky, Ronald D Cohn, Craig Campbell

Paediatrics Publications

Pediatric neuromuscular diseases encompass all disorders with onset in childhood and where the primary area of pathology is in the peripheral nervous system. These conditions are largely genetic in etiology, and only those with a genetic underpinning will be presented in this review. This includes disorders of the anterior horn cell (e.g., spinal muscular atrophy), peripheral nerve (e.g., Charcot-Marie-Tooth disease), the neuromuscular junction (e.g., congenital myasthenic syndrome), and the muscle (myopathies and muscular dystrophies). Historically, pediatric neuromuscular disorders have uniformly been considered to be without treatment possibilities and to have dire prognoses. This perception has gradually changed, starting in part …

The Turkish Version Of The Juvenile Arthritis Multidimensional Assessment Report (Jamar), Erkan Demirkaya, Seza Ozen, Betul Sozeri, Nuray Aktay Ayaz, Ozgur Kasapcopur, Erbil Unsal, Balahan Bora Makay, Kenan Barut, Berna Eren Fidanci, Dogan Simsek, Mustafa Cakan, Alessandro Consolaro, Francesca Bovis, Nicolino Ruperto

Paediatrics Publications

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Turkish language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to …

Circulatory Insufficiency And Hypotension Related To The Ductus Arteriosus In Neonates, Danielle R Rios, Soume Bhattacharya, Philip T Levy, Patrick J Mcnamara

Paediatrics Publications

The biological role of the ductus arteriosus (DA) in neonates varies from an innocent bystander role during normal postnatal transition, to a supportive role when there is compromise to either systemic or pulmonary blood flow, to a pathological state in the presence of hemodynamically significant systemic to pulmonary shunts, as occurs in low birth weight infants. Among a wide array of clinical manifestations arising due to the ductal entity, systemic circulatory insufficiency and hypotension are of significant concern as they are particularly challenging to manage. An understanding of the physiologic interplay between the DA and the circulatory system is the …

Treatment-Related Mortality In Newly Diagnosed Pediatric Cancer: A Population-Based Analysis., Paul Gibson, Jason D Pole, Tanya Lazor, Donna Johnston, Carol Portwine, Mariana Silva, Sarah Alexander, Lillian Sung

Paediatrics Publications

Using a previously developed reliable and valid treatment-related mortality (TRM) definition, our objective was to describe the proportion of children newly diagnosed with cancer experiencing TRM and to identify risk factors for TRM in a population-based cohort. We included children with cancerincluded, 179 had TRM, 478 died of progressive disease, and 4522 were still alive. At 5 years, the cumulative incidence of TRM among the entire cohort was 3.9% (95% confidence interval (CI) 3.3-4.5%). When compared to brain tumor patients, leukemia and lymphoma patients had a significantly higher risk of TRM (hazard ratio (HR) 2.5, 95% CI: 1.6-4.0; P < 0.0001). Infants were at significantly higher risk of TRM across diagnostic groups. Other factors associated with higher risks of TRM were metastatic disease (P < 0.0001), diagnosis prior to 1 January 2008 (P = 0.001), hematopoietic stem cell transplantation (HSCT) (P < 0.0001), and relapse (P < 0.0001). The 5-year cumulative incidence of TRM was 3.9% among newly diagnosed children with cancer. Infants were at higher risk of TRM across diagnostic groups. Other risk factors for TRM were leukemia or lymphoma, metastatic disease, earlier diagnosis year, HSCT, and relapse. Future work should further refine prognostic factors by specific cancer diagnosis to best understand when and how to intervene to improve outcomes.

Treatment-Related Mortality In Newly Diagnosed Pediatric Cancer: A Population-Based Analysis, Paul Gibson, Jason D Pole, Tanya Lazor, Donna Johnston, Carol Portwine, Mariana Silva, Sarah Alexander, Lillian Sung

Paediatrics Publications

Using a previously developed reliable and valid treatment-related mortality (TRM) definition, our objective was to describe the proportion of children newly diagnosed with cancer experiencing TRM and to identify risk factors for TRM in a population-based cohort. We included children with cancerincluded, 179 had TRM, 478 died of progressive disease, and 4522 were still alive. At 5 years, the cumulative incidence of TRM among the entire cohort was 3.9% (95% confidence interval (CI) 3.3-4.5%). When compared to brain tumor patients, leukemia and lymphoma patients had a significantly higher risk of TRM (hazard ratio (HR) 2.5, 95% CI: 1.6-4.0; P < 0.0001). Infants were at significantly higher risk of TRM across diagnostic groups. Other factors associated with higher risks of TRM were metastatic disease (P < 0.0001), diagnosis prior to 1 January 2008 (P = 0.001), hematopoietic stem cell transplantation (HSCT) (P < 0.0001), and relapse (P < 0.0001). The 5-year cumulative incidence of TRM was 3.9% among newly diagnosed children with cancer. Infants were at higher risk of TRM across diagnostic groups. Other risk factors for TRM were leukemia or lymphoma, metastatic disease, earlier diagnosis year, HSCT, and relapse. Future work should further refine prognostic factors by specific cancer diagnosis to best understand when and how to intervene to improve outcomes.

Nusinersen Versus Sham Control In Later-Onset Spinal Muscular Atrophy., Eugenio Mercuri, Basil T Darras, Claudia A Chiriboga, John W Day, Craig Campbell, Anne M Connolly, Susan T Iannaccone, Janbernd Kirschner, Nancy L Kuntz, Kayoko Saito, Perry B Shieh, Már Tulinius, Elena S Mazzone, Jacqueline Montes, Kathie M Bishop, Qingqing Yang, Richard Foster, Sarah Gheuens, C Frank Bennett, Wildon Farwell, Eugene Schneider, Darryl C De Vivo, Richard S Finkel

Paediatrics Publications

BACKGROUND: Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 ( SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA).

METHODS: We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2:1 ratio, to undergo intrathecal administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274. The primary end point was …

Nusinersen Versus Sham Control In Later-Onset Spinal Muscular Atrophy, Eugenio Mercuri, Basil T Darras, Claudia A Chiriboga, John W Day, Craig Campbell, Anne M Connolly, Susan T Iannaccone, Janbernd Kirschner, Nancy L Kuntz, Kayoko Saito, Perry B Shieh, Már Tulinius, Elena S Mazzone, Jacqueline Montes, Kathie M Bishop, Qingqing Yang, Richard Foster, Sarah Gheuens, C Frank Bennett, Wildon Farwell, Eugene Schneider, Darryl C De Vivo, Richard S Finkel

Paediatrics Publications

Background

Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 ( SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA).

Methods

We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2:1 ratio, to undergo intrathecal administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274. The primary end point was …

Peripheral Blood Epi-Signature Of Claes-Jensen Syndrome Enables Sensitive And Specific Identification Of Patients And Healthy Carriers With Pathogenic Mutations In Kdm5c, Laila C Schenkel, Erfan Aref-Eshghi, Cindy Skinner, Peter Ainsworth, Hanxin Lin, Guillaume Paré, David I Rodenhiser, Charles Schwartz, Bekim Sadikovic

Paediatrics Publications

Background

Claes-Jensen syndrome is an X-linked inherited intellectual disability caused by mutations in the

Results

Genome-wide DNA methylation analysis of 7 male patients affected with Claes-Jensen syndrome and 56 age- and sex-matched controls identified a specific DNA methylation defect (epi-signature) in the peripheral blood of these patients, including 1769 individual CpGs and 9 genomic regions. Six healthy female carriers showed less pronounced but distinctive changes in the same regions enabling their differentiation from both patients and controls. Highly specific computational model using the most significant methylation changes demonstrated 100% accuracy in differentiating patients, carriers, and controls in the training cohort, …

Eculizumab Dosing In Infants, M Kobrzynski, B Wile, S S Huang, G Filler

Paediatrics Publications

Eculizumab is the therapy of choice for patients with atypical hemolytic uremic syndrome (aHUS). Dosing recommendations stem from two trials: one retrospective trial (19 children and 5 infants) and one prospective trial (22 patients and 5 infants). This case report highlights the need for more precise dosing recommendations in children, particularly in infants, and for smaller vials of the medication to facilitate more precise dosing. Such changes would ensure that adverse events are minimized and that the children with aHUS who are treated with eculizumab experience an optimal clinical response.

Pura Syndrome: Clinical Delineation And Genotype-Phenotype Study In 32 Individuals With Review Of Published Literature, Margot R F Reijnders, Robert Janowski, Mohsan Alvi, Jay E Self, Ton J Van Essen, Maaike Vreeburg, Rob P W Rouhl, Servi J C Stevens, Alexander P A Stegmann, Jolanda Schieving, Rolph Pfundt, Katinke Van Dijk, Eric Smeets, Connie T R M Stumpel, Levinus A Bok, Jan Maarten Cobben, Marc Engelen, Sahar Mansour, Margo Whiteford, Kate E Chandler, Sofia Douzgou, Nicola S Cooper, Ene-Choo Tan, Roger Foo, Angeline H M Lai, Julia Rankin, Andrew Green, Tuula Lönnqvist, Pirjo Isohanni, Shelley Williams, Ilene Ruhoy, Karen S Carvalho, James J Dowling, Dorit L Lev, Katalin Sterbova, Petra Lassuthova, Jana Neupauerová, Jeff L Waugh, Sotirios Keros, Jill Clayton-Smith, Sarah F Smithson, Han G Brunner, Ceciel Van Hoeckel, Mel Anderson, Virginia E Clowes, Victoria Mok Siu, The Ddd Study, Paulo Selber, Richard J Leventer, Christoffer Nellaker, Dierk Niessing, David Hunt, Diana Baralle

Paediatrics Publications

BACKGROUND: De novo mutations in

OBJECTIVES: To delineate the clinical spectrum of PURA syndrome and study genotype-phenotype correlations.

METHODS: Diagnostic or research-based exome or Sanger sequencing was performed in individuals with ID. We systematically collected clinical and mutation data on newly ascertained PURA syndrome individuals, evaluated data of previously reported individuals and performed a computational analysis of photographs. We classified mutations based on predicted effect using 3D in silico models of crystal structures of

RESULTS: We report mutations in

CONCLUSION: We delineate the clinical spectrum of PURA syndrome with the identification of 32 additional individuals. The identification of one individual …