ABSTRACT
Down syndrome is one of the most common conditions encountered in the genetics clinic. Due to improvements in healthcare, educational opportunities, and community inclusion over the past 30 years, the life expectancy and quality of life for individuals with Down syndrome have significantly improved. As prenatal screening and diagnostic techniques have become more enhanced and widely available, genetic counselors can expect to frequently provide information and support following a new diagnosis of Down syndrome. This guideline was written for genetic counselors and other healthcare providers regarding the communication of a diagnosis of Down syndrome to ensure that families are consistently given up-to-date and balanced information about the condition, delivered in a supportive and respectful manner.
Subject(s)
Down Syndrome/diagnosis , Genetic Counseling , Prenatal Diagnosis , Down Syndrome/physiopathology , Humans , Quality of Life , WorkforceABSTRACT
OBJECTIVES: To determine the prevalence of iron deficiency (ID) and iron deficiency anemia (IDA) in a sample of children with Down syndrome (DS) and to evaluate the effect of macrocytosis on the diagnosis of ID/IDA in these children. STUDY DESIGN: Children with DS ≥ 12 months of age who were followed at the Duke University Medical Center Comprehensive DS Clinic from December 2004 to March 2007 were screened for ID/IDA with a complete blood count, reticulocyte count, iron panel, and erythrocytic protoporphyrins. RESULTS: A total of 114 children were enrolled, with a median age of 4.7 years. ID was identified in 12 subjects (10%), and IDA was identified in 3 subjects (3%). ID/IDA would not have been accurately diagnosed in 13 of 15 subjects (86%) if red blood cell (RBC) indices alone had been used for screening. Abnormal RBC indices with low transferrin saturation were 100% sensitive for ID/ IDA screening. CONCLUSIONS: Prevalence of ID/IDA in children with DS was comparable with that in the general pediatric population. Macrocytosis had implications for screening of ID/IDA with only RBC indices. We suggest ID/IDA screening in DS children be done with a laboratory panel at least including complete blood count, reticulocyte count, transferrin saturation, and serum ferritin.
Subject(s)
Anemia, Iron-Deficiency/epidemiology , Anemia, Iron-Deficiency/etiology , Down Syndrome/complications , Iron Deficiencies , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Prevalence , Prospective Studies , Young AdultABSTRACT
Individuals with Down syndrome (DS) exhibit a cholinergic deficiency similar to that found in Alzheimer's disease. Cholinesterase inhibitors, used to treat Alzheimer's disease, may improve cognitive function in individuals with DS. This is the first investigation of the safety and efficacy of rivastigmine (an acetyl and butyryl cholinesterase inhibitor) on specific cognitive domains in pediatric DS. Eleven subjects with DS (ages 10-17 years) were treated with a liquid formulation of rivastigmine. Four subjects experienced no adverse events (AEs). Seven subjects reported AEs that were mild, transient and consistent with adverse events typically noted with cholinesterase inhibitors. Significant improvements were found in overall adaptive function (Vineland Adaptive Behavior Scales and Clinician's Interview-Based Impression of Change), attention (Leiter Attention Sustained tests A and B), memory (NEPSY: Narrative and Immediate Memory for Names subtests) and language (Test of Verbal Expression and Reasoning and Clinical Evaluation of Language Fundamentals-Preschool) domains. Improved language performance was found across all functional levels. These results underscore the need for larger, controlled studies employing a carefully constructed test battery capable of measuring the full scope of performance across multiple domains and a wide range of functional levels.
Subject(s)
Cholinesterase Inhibitors/therapeutic use , Down Syndrome/drug therapy , Phenylcarbamates/therapeutic use , Adaptation, Psychological/drug effects , Adolescent , Attention/drug effects , Child , Cholinesterase Inhibitors/administration & dosage , Cholinesterase Inhibitors/adverse effects , Down Syndrome/psychology , Female , Humans , Language , Male , Memory/drug effects , Patient Compliance , Phenylcarbamates/administration & dosage , Phenylcarbamates/adverse effects , Rivastigmine , Verbal Behavior/drug effectsABSTRACT
Over a 10-year period in a Down syndrome Clinic, 11 children and adolescents were encountered with a history of new-onset (8) or worsening (3) autistic characteristics. Ten of the 11 (91%) had cognitive decline to a dementia-like state and 9 of the 11 (82%) new-onset insomnia. The mean age at which symptoms developed was 11.4 years (standard deviation = 3.6 years; range 5-14 years), an older age than usual for autistic regression in Down syndrome. Ten of 11 cases (91%) had elevated ("positive") thyroperoxidase antibody titers compared to only 5 of 21 (23%) age-matched control subjects with Down syndrome (P < .001). At follow-up at a mean age of 20.7 years (standard deviation = 3.9 years), 8 of the 11 (73%) were at least somewhat better. Down syndrome disintegrative disorder seems an appropriate name for this newly recognized clinical association, which may be due to autoimmunity.
Subject(s)
Dementia/etiology , Developmental Disabilities/etiology , Down Syndrome/complications , Regression, Psychology , Sleep Initiation and Maintenance Disorders/etiology , Adolescent , Child , Child, Preschool , Cognition Disorders , Female , Follow-Up Studies , Humans , Male , Thyroid Gland/immunology , Thyroid Gland/pathologyABSTRACT
Following the completion of a 20-week, open-label study of the safety and efficacy of liquid rivastigmine for adolescents with Down syndrome, 5 of the 10 adolescents in the clinical trial continued long-term rivastigmine therapy and 5 did not. After an average period of 38 months, all 10 subjects returned for a follow-up assessment to determine the safety and efficacy of long-term rivastigmine use. Rivastigmine was well tolerated and overall health appeared to be unaffected by long-term rivastigmine use. Performance change on cognitive and language measures administered at the termination of the open-label clinical trial was compared between the two groups. No between-group difference in median performance change across the long-term period was found, suggesting that the long-term use of rivastigmine does not improve cognitive and language performance. However, two subjects demonstrated remarkable improvement in adaptive function over the long-term period. Both subjects had received long-term rivastigmine therapy. The discussion addresses the challenge of assessing cognitive change in clinical trials using adolescents with Down syndrome as subjects and the use of group versus individual data to evaluate the relevance of medication effects.
Subject(s)
Cognition/drug effects , Down Syndrome/drug therapy , Neuroprotective Agents/therapeutic use , Phenylcarbamates/therapeutic use , Adolescent , Follow-Up Studies , Humans , Language Disorders/drug therapy , Language Disorders/etiology , Language Tests , Male , Neuroprotective Agents/adverse effects , Phenylcarbamates/adverse effects , Rivastigmine , Time FactorsABSTRACT
There is growing evidence to support the use of early central cholinergic enhancement to improve cognitive functioning in individuals with Down syndrome (DS). This report summarizes preliminary safety and cognitive efficacy data for seven children (8-13 years) with DS who participated in a 22-week, open-label trial of donepezil hydrochloride. Donepezil was dosed once daily at 2.5 mg and, based on tolerability, increased to 5 mg/day. Safety assessments were conducted at Week 1 (baseline), Week 8 (2.5 mg donepezil), Week 16 (5 mg) and Week 22 (after the donepezil had been discontinued). Measures of cognitive function were administered at each visit, encompassing the following domains: memory; attention; mood; and adaptive functioning. Donepezil was well tolerated at the 2.5 and 5 mg doses. The side effects were mild, transient, and consistent with the adverse events noted with cholinesterase inhibitors. Some children showed improvement on measures of memory (NEPSY Memory for Names and Narrative Memory) and sustained attention to tasks (Conners' Parent Rating Scales), although increased irritability and/or assertiveness were noted in some patients. Overall, this clinical report series adds to our initial findings of language gains in children with DS treated with donepezil. It also supports the need for larger, double-blind studies of the safety and efficacy of donepezil and other cholinesterase inhibitors for children with DS.
Subject(s)
Cholinesterase Inhibitors/therapeutic use , Cognition/drug effects , Down Syndrome/drug therapy , Indans/therapeutic use , Piperidines/therapeutic use , Adolescent , Child , Cholinesterase Inhibitors/administration & dosage , Cholinesterase Inhibitors/adverse effects , Donepezil , Down Syndrome/diagnosis , Drug Administration Schedule , Female , Humans , Indans/administration & dosage , Indans/adverse effects , Male , Piperidines/administration & dosage , Piperidines/adverse effects , Treatment OutcomeABSTRACT
Clinical and translational research play a key role in the transition of basic research discoveries to effective therapies. In Down syndrome (DS), these research approaches are not well utilized or developed to test new therapies to improve cognitive and/or adaptive function in this population. This article reviews the history of clinical trial research in children with DS from a cognitive research perspective and discusses important issues relevant to the conduct of well designed clinical trials for this population. Specific issues addressed include: funding, study design, study medication, subject recruitment and retention, safety, and efficacy challenges. The Duke Down Syndrome Research Team's program of clinical research of cholinesterase inhibitors for individuals with DS serves as the model application for the identified research principles. It is hoped that this article will raise awareness of the unmet need for clinical research in the cognitive and adaptive function of individuals with DS, especially children with DS.
Subject(s)
Cognition , Down Syndrome/psychology , Child , Clinical Protocols , Clinical Trials as Topic/methods , Cognition Disorders/drug therapy , Cognition Disorders/etiology , Cognition Disorders/psychology , Down Syndrome/complications , Down Syndrome/drug therapy , Humans , Nootropic Agents/therapeutic use , Patient Selection , Research DesignABSTRACT
Los autores de este reciente trabajo describen un complejo cuadro que aparece raramente en el síndrome de Down, para el que proponen el término 'trastorno desintegrativo en el síndrome de Down'. Se caracterizaría en esencia por la aparición de: 1) una regresión de tipo autista en un niño con síndrome de Down que hasta entonces había tenido un desarrollo conductual y lingüístico normales, dentro de su síndrome, 2) declive cognitivo hacia un estado de demencia, 3) insomnio, 4) aparición a edades mayores de las que suelen ocurrir en la típica regresión autista del síndrome de Down, 5) quizá, signos de autoinmunidad tiroidea. El llamado trastorno desintegrativo infantil forma parte de un grupo más amplio denominado: 'Trastornos generalizados del desarrollo' (DSM-IV R). Se caracteriza por el desarrollo de autismo y de deterioro cognitivo en un niño hasta entonces normal, y que aparece a una edad superior a la que suele aparecer en la típica regresión autista. Para hacer este diagnóstico, debe haber pasado por lo menos 2 años con un desarrollo normal, apareciendo después la regresión autista; esta regresión debe ocurrir antes de los 10 años de edad y no debe ser explicada por ningún otro diagnóstico en ese niño. Como tal, el trastorno desintegrativo es una enfermedad rara. Lo que se presenta en este trabajo es un análisis de 11 casos observados en una Clínica especializada en el síndrome de Down (Duke University Medical Center, Durham, USA) a lo largo de 10 años (2002-2012), cuya descripción se aproxima al diagnóstico antes definido como trastorno desintegrativo infantil, pero con unas características propias que inducen a los autores a proponer una nueva entidad patológica que definen como trastorno desintegrativo en el (o propio del) síndrome de Down. Para entrar en este diagnóstico, los pacientes tenían que presentar regresión autista de acuerdo con los requisitos diagnósticos de DSM-IV R, y tener una edad superior a la que se considera propia de la regresión autista en el síndrome de Down (5 años o más). En todos los casos se pidió a los padres una historia del declive cognitivo hacia un estado del tipo de la demencia (desarrollo cognitivo, desarrollo del lenguaje, desarrollo de motricidad gruesa; desarrollo de habilidades de la vida cotidiana). Se les pidió los registros escolares y muestras del trabajo escolar antes y después del inicio del declive cognitivo, para comprobar el deterioro del niño. También se les pidió la historia del insomnio. En una segunda y posteriores visitas se les volvió a pedir historias detalladas del declive cognitivo y de nuevos síntomas autistas, para confirmar lo ya informado. Seles realizaron pruebas de seropositividad a la tiroperoxidasa (AU)
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