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1.
Codas ; 31(4): e20180177, 2019 Aug 22.
Artigo em Português, Inglês | MEDLINE | ID: mdl-31460569

RESUMO

PURPOSE: This study aimed to present findings on language, behavior, and neurodevelopment in a girl diagnosed with Angelman Syndrome, evaluated when she was three and eight years old. METHODS: The following evaluation instruments were used: Observation of Communication Behavior, Early Language Milestone (ELM) Scale, and Denver Developmental Screening Test, 2nd edition (DDST-II). RESULTS: In this case report, presence of AS phenotype signals such as wide mouth and wide-spaced teeth, tongue thrusting, strabismus, up slanting palpebral fissures, and sialorrhea are verified. Expressive and receptive deficits were verified in the language assessment, with the absence of orality and loss of comprehension with very similar performances in both evaluations. The ELM and DDST-II tests indicated severe impairment of all abilities evaluated at both three and eight years of age. Performance was quite similar in both evaluations in all areas of child development. Little progress was observed over time despite the great therapeutic and educational investment. CONCLUSION: The presence of a complex scenario such as AS demands high complexity clinical needs, a situation that is worsened due to scarcity of therapeutic resources that could minimize the harmful impacts of AS and culminate in increased quality of life for the AS population and their families.


Assuntos
Síndrome de Angelman/reabilitação , Transtornos do Neurodesenvolvimento/reabilitação , Síndrome de Angelman/diagnóstico , Síndrome de Angelman/psicologia , Criança , Desenvolvimento Infantil , Comunicação , Feminino , Humanos , Desenvolvimento da Linguagem , Testes de Linguagem , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/psicologia , Testes Neuropsicológicos , Desempenho Psicomotor
2.
Nat Neurosci ; 22(8): 1235-1247, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31235931

RESUMO

Mutations affecting the gene encoding the ubiquitin ligase UBE3A cause Angelman syndrome. Although most studies focus on the synaptic function of UBE3A, we show that UBE3A is highly enriched in the nucleus of mouse and human neurons. We found that the two major isoforms of UBE3A exhibit highly distinct nuclear versus cytoplasmic subcellular localization. Both isoforms undergo nuclear import through direct binding to PSMD4 (also known as S5A or RPN10), but the amino terminus of the cytoplasmic isoform prevents nuclear retention. Mice lacking the nuclear UBE3A isoform recapitulate the behavioral and electrophysiological phenotypes of Ube3am-/p+ mice, whereas mice harboring a targeted deletion of the cytosolic isoform are unaffected. Finally, we identified Angelman syndrome-associated UBE3A missense mutations that interfere with either nuclear targeting or nuclear retention of UBE3A. Taken together, our findings elucidate the mechanisms underlying the subcellular localization of UBE3A, and indicate that the nuclear UBE3A isoform is the most critical for the pathophysiology of Angelman syndrome.


Assuntos
Síndrome de Angelman/genética , Síndrome de Angelman/psicologia , Comportamento Animal , Ubiquitina-Proteína Ligases/genética , Animais , Proteínas de Transporte/metabolismo , Núcleo Celular/enzimologia , Núcleo Celular/genética , Citosol/enzimologia , Fenômenos Eletrofisiológicos/genética , Feminino , Humanos , Isoenzimas/genética , Masculino , Camundongos , Camundongos Knockout , Mutação de Sentido Incorreto/genética , Comportamento de Nidação , Neurônios/enzimologia , Desempenho Psicomotor , Natação/psicologia , Dedos de Zinco
3.
Dev Neurorehabil ; 22(8): 516-526, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31116614

RESUMO

Purpose: This study was designed to assess memory, imitation of motor actions and motor performance by 12 children (age range 40-151 months) with Angelman syndrome (AS), a rare neurogenetic disorder associated with learning and memory impairments. Methods: Children's functioning was assessed at several time points over a 3-month period. Results: Memory and motor performance tests had acceptable test-retest and inter-rater reliability whereas the motor imitation test did not. Children were able to recall action sequences after a 24-h delay. Memory and motor performance scores were correlated with children's chronological age and raw scores on subdomains of the Vineland-II. Conclusions: These behavioral tests require further development and evaluation but may show promise to accompany standardized assessments that are currently in use with children with AS.


Assuntos
Síndrome de Angelman/diagnóstico , Comportamento Imitativo , Memória , Destreza Motora , Síndrome de Angelman/psicologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Testes Neuropsicológicos/normas , Reprodutibilidade dos Testes
4.
Dev Med Child Neurol ; 61(11): 1266-1274, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31074506

RESUMO

AIM: A scoping review was conducted to examine and evaluate empirical data on the communication profile of Angelman syndrome beyond the described dissociation between receptive language and speech. METHOD: Three databases (PsycINFO, Embase, and Web of Science) were searched to retrieve articles investigating communication in Angelman syndrome. Seventeen articles investigating the broader communication profile were found; their methodology was evaluated against quality criteria. RESULTS: Despite the absence of speech, individuals with Angelman syndrome have a wide repertoire of non-verbal communicative behaviours, mainly characterized by gestures, although advanced forms such as symbolic communication are used by some individuals. The use of communicative forms differs between the genetic aetiologies of Angelman syndrome; individuals with non-deletion aetiologies typically have greater communicative abilities. INTERPRETATION: The broader communication profile of Angelman syndrome is characterized by diverse and multimodal abilities, including some use of symbolic forms of communication that appears atypical given the absence of speech. This is suggestive of a probable dissociation between speech and other expressive forms of communication, indicating an isolated speech production impairment. This highlights a need in this population for alternative communication and specific input from services tailored to support the nuances of the communication profile of Angelman syndrome. WHAT THIS PAPER ADDS: Although absent speech is near universal, a diverse profile of other communicative abilities has been reported. Parental reporting has been predominantly used to assess the communication profile of Angelman syndrome. Literature that investigates the specificities and possible dissociations in such a communication profile is limited.


Assuntos
Síndrome de Angelman/psicologia , Comunicação , Síndrome de Angelman/epidemiologia , Humanos , Comunicação não Verbal , Fala
5.
J Autism Dev Disord ; 49(4): 1717-1726, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30542941

RESUMO

Children with neurogenetic syndromes (NGS) experience comorbid challenging behaviors and psychopathology. We examined challenging behaviors in 86 toddlers and preschoolers across three NGS [Angelman syndrome (AS), Prader-Willi syndrome (PWS), and Williams syndrome (WS)] and 43 low-risk controls (LRC), using the Child Behavior Checklist for Ages 1½-5. Challenging behavior profiles differed across NGS, with generally elevated behaviors in AS and WS, but not PWS, relative to LRC. Withdrawn and autism spectrum symptoms were particularly elevated in AS. Although several profiles were similar to those previously reported in older children and adults, we also observed inconsistencies that suggest non-linear developmental patterns of challenging behaviors. These findings underscore the importance of characterizing early challenging behaviors to inform atypical phenotypic development and targeted intervention.


Assuntos
Síndrome de Angelman/psicologia , Transtornos do Comportamento Infantil/psicologia , Síndrome de Prader-Willi/psicologia , Síndrome de Williams/psicologia , Síndrome de Angelman/diagnóstico , Síndrome de Angelman/epidemiologia , Transtornos do Comportamento Infantil/diagnóstico , Transtornos do Comportamento Infantil/epidemiologia , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Síndrome de Prader-Willi/diagnóstico , Síndrome de Prader-Willi/epidemiologia , Relatório de Pesquisa , Síndrome de Williams/diagnóstico , Síndrome de Williams/epidemiologia
6.
Neuropharmacology ; 144: 337-344, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30408487

RESUMO

NSI-189 Phosphate, (4-benzylpiperazin-1-yl)-[2-(3-methyl-butylamino)pyridin-3-yl] methanone is a new chemical entity under development for the treatment of MDD, based upon preclinical data demonstrating stimulation of neurogenesis of human hippocampus-derived neural stem cells in vitro and in mouse hippocampus in vivo. Previous studies have examined the tolerability and efficacy of NSI-189 for treating major depressive disorder (MDD). NSI-189 has shown significant potential as a treatment for MDD, with concurrent improvement of a cognition scale in a small double-blind, placebo-controlled study. The current study evaluated its possible application for the treatment of Angelman Syndrome. Incubation of acute hippocampal slices from wild-type mice with NSI-189 resulted in a time- and dose-dependent increase in the magnitude of long-term potentiation (LTP) elicited by theta burst stimulation (TBS). The same protocol enhanced TBS-induced LTP in acute hippocampal slices from AS mice. A short treatment with daily injections of NSI-189 in AS mice reversed impairments in cognitive and motor functions, while it slightly enhanced performance of WT mice. The effects of NSI-189 on synaptic plasticity and cognitive functions were associated with activation of the TrkB and Akt pathways. These results suggest that NSI-189 could represent a potential treatment for AS patients.


Assuntos
Aminopiridinas/farmacologia , Síndrome de Angelman/tratamento farmacológico , Fármacos do Sistema Nervoso Central/farmacologia , Cognição/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Potenciação de Longa Duração/efeitos dos fármacos , Piperazinas/farmacologia , Síndrome de Angelman/fisiopatologia , Síndrome de Angelman/psicologia , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Hipocampo/fisiopatologia , Masculino , Camundongos Transgênicos , Atividade Motora/efeitos dos fármacos , Técnicas de Cultura de Tecidos
7.
Brain Cogn ; 128: 73-79, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30471990

RESUMO

The combination of intellectual, communicative, and motor deficits limit the use of standardized behavioral assessments of cognition in individuals with Angelman syndrome (AS). The current study is the first to objectively evaluate learning and memory in AS using auditory event-related potentials (ERP) during passive exposure to spoken stimuli. Fifteen nonverbal individuals with the deletion subtype of AS (age 4-45 years) completed the auditory incidental memory paradigm. Auditory ERPs were recorded in response to a sequence of unfamiliar nonwords, in which one randomly selected stimulus was repeated multiple times and the rest were presented once. Larger parietal responses within 200-500 ms for the repeated nonword compared to novel distracters were associated with caregiver reports of more adaptive communication skills. These findings demonstrate good tolerability of ERP procedures (94% success rate) and indicate that persons with AS can acquire new information following repeated auditory exposure, even in the absence of explicit memorization instructions. Strong associations between the caregiver reports of adaptive functioning and neural indices of auditory learning and memory support the utility of brain-based measures for objectively evaluating higher-order information processing in nonverbal persons with neurodevelopmental disorders.


Assuntos
Síndrome de Angelman/psicologia , Cognição/fisiologia , Potenciais Evocados Auditivos/fisiologia , Aprendizagem/fisiologia , Memória/fisiologia , Adolescente , Adulto , Síndrome de Angelman/fisiopatologia , Encéfalo/fisiopatologia , Criança , Pré-Escolar , Eletroencefalografia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
Mol Autism ; 9: 47, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30220990

RESUMO

Background: Angelman syndrome (AS) is a neurodevelopmental disorder caused by mutations affecting UBE3A function. AS is characterized by intellectual disability, impaired motor coordination, epilepsy, and behavioral abnormalities including autism spectrum disorder features. The development of treatments for AS heavily relies on the ability to test the efficacy of drugs in mouse models that show reliable, and preferably clinically relevant, phenotypes. We previously described a number of behavioral paradigms that assess phenotypes in the domains of motor performance, repetitive behavior, anxiety, and seizure susceptibility. Here, we set out to evaluate the robustness of these phenotypes when tested in a standardized test battery. We then used this behavioral test battery to assess the efficacy of minocycline and levodopa, which were recently tested in clinical trials of AS. Methods: We combined data of eight independent experiments involving 111 Ube3a mice and 120 wild-type littermate control mice. Using a meta-analysis, we determined the statistical power of the subtests and the effect of putative confounding factors, such as the effect of sex and of animal weight on rotarod performance. We further assessed the robustness of these phenotypes by comparing Ube3a mutants in different genetic backgrounds and by comparing the behavioral phenotypes of independently derived Ube3a-mutant lines. In addition, we investigated if the test battery allowed re-testing the same animals, which would allow a within-subject testing design. Results: We find that the test battery is robust across different Ube3a-mutant lines, but confirm and extend earlier studies that several phenotypes are very sensitive to genetic background. We further found that the audiogenic seizure susceptibility phenotype is fully reversible upon pharmacological treatment and highly suitable for dose-finding studies. In agreement with the clinical trial results, we found that minocycline and levodopa treatment of Ube3a mice did not show any sign of improved performance in our test battery. Conclusions: Our study provides a useful tool for preclinical drug testing to identify treatments for Angelman syndrome. Since the phenotypes are observed in several independently derived Ube3a lines, the test battery can also be employed to investigate the effect of specific Ube3a mutations on these phenotypes.


Assuntos
Síndrome de Angelman/genética , Síndrome de Angelman/psicologia , Escala de Avaliação Comportamental , Ubiquitina-Proteína Ligases/genética , Animais , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Levodopa/farmacologia , Masculino , Camundongos Mutantes , Minociclina/farmacologia , Mutação , Fenótipo
9.
Am J Intellect Dev Disabil ; 123(3): 241-253, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29671635

RESUMO

It is well documented that mothers of children with challenging behavior (CB) experience elevated levels of stress and that this persists over time, but less is known about the experience of mothers of children with rare genetic syndromes. This article describes 2 studies, 1 cross-sectional and 1 longitudinal, comparing well-being in mothers of children with Angelman, Cornelia de Lange and Cri du Chat syndrome who have either shown chronic CB ( n = 18) or low/no CB ( n = 26) in the preceding 7 years. The presence of chronic, long-term CB increased maternal stress but not depression or anxiety, and did not influence positive well-being. Stress relating specifically to their child's genetic syndrome reduced with age, highlighting the need for further exploration in this area.


Assuntos
Síndrome de Angelman , Ansiedade/psicologia , Síndrome do Miado do Gato , Síndrome de Lange , Depressão/psicologia , Saúde Mental , Mães/psicologia , Comportamento Problema , Estresse Psicológico/psicologia , Atividades Cotidianas , Adolescente , Adulto , Síndrome de Angelman/fisiopatologia , Síndrome de Angelman/psicologia , Estudos de Casos e Controles , Criança , Síndrome do Miado do Gato/fisiopatologia , Síndrome do Miado do Gato/psicologia , Estudos Transversais , Síndrome de Lange/fisiopatologia , Síndrome de Lange/psicologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Comportamento Problema/psicologia , Doenças Raras , Adulto Jovem
10.
J Neurosci ; 38(11): 2671-2682, 2018 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-29431654

RESUMO

Angelman syndrome (AS), a neurodevelopmental disorder associated with intellectual disability, is caused by loss of maternal allele expression of UBE3A in neurons. Mouse models of AS faithfully recapitulate disease phenotypes across multiple domains, including behavior. Yet in AS, there has been only limited study of behaviors encoded by the prefrontal cortex, a region broadly involved in executive function and cognition. Because cognitive impairment is a core feature of AS, it is critical to develop behavioral readouts of prefrontal circuit function in AS mouse models. One such readout is behavioral extinction, which has been well described mechanistically and relies upon prefrontal circuits in rodents. Here we report exaggerated operant extinction in male AS model mice, concomitant with enhanced excitability in medial prefrontal neurons from male and female AS model mice. Abnormal behavior was specific to operant extinction, as two other prefrontally dependent tasks (cued fear extinction and visuospatial discrimination) were largely normal in AS model mice. Inducible deletion of Ube3a during adulthood was not sufficient to drive abnormal extinction, supporting the hypothesis that there is an early critical period for development of cognitive phenotypes in AS. This work represents the first formal experimental analysis of prefrontal circuit function in AS, and identifies operant extinction as a useful experimental paradigm for modeling cognitive aspects of AS in mice.SIGNIFICANCE STATEMENT Prefrontal cortex encodes "high-level" cognitive processes. Thus, understanding prefrontal function is critical in neurodevelopmental disorders where cognitive impairment is highly penetrant. Angelman syndrome is a neurodevelopmental disorder associated with speech and motor impairments, an outwardly happy demeanor, and intellectual disability. We describe a behavioral phenotype in a mouse model of Angelman syndrome and related abnormalities in prefrontal cortex function. We hypothesize that robust and reliable prefrontally encoded behavior may be used to model cognitive impairments in Angelman syndrome.


Assuntos
Síndrome de Angelman/psicologia , Condicionamento Operante , Extinção Psicológica , Córtex Pré-Frontal/fisiopatologia , Síndrome de Angelman/fisiopatologia , Animais , Cognição , Transtornos Cognitivos/genética , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Sinais (Psicologia) , Função Executiva , Deleção de Genes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Técnicas de Patch-Clamp , Fenótipo , Ubiquitina-Proteína Ligases/genética
11.
Am J Med Genet A ; 176(5): 1099-1107, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28944563

RESUMO

Treatment for Angelman syndrome (AS) is currently limited to symptomatic interventions. A mouse model of AS has reduced calcium/calmodulin-dependent kinase II activity due to excessive phosphorylation of specific threonine residues, leading to diminished long-term potentiation. In a rat model of Parkinson disease, levodopa reduced phosphorylation of various proteins, including calcium/calmodulin-dependent kinase II. Further studies demonstrated that AS mice treated with levodopa performed better on rotarod testing than untreated AS mice. We conducted a multi-center double-blind randomized placebo-controlled 1-year trial of levodopa / carbidopa with either 10 or 15 mg/kg/day of levodopa in children with AS. The outcome of this intervention was assessed using either the Bayley Scales of Infant Development or the Mullen Scales of Early Learning, as well as the Vineland Adaptive Behavior Scales, and the Aberrant Behavior Checklist. Of the 78 participants enrolled, 67 participants received study medication (33 on levodopa, 34 on placebo), and 55 participants (29 on levodopa, 26 on placebo) completed the 1-year study. There were no clinically or statistically significant changes in any of the outcome measures over a 1-year period comparing the levodopa and placebo groups. The number of adverse events reported, including the more serious adverse events, was similar in both groups, but none were related to treatment with levodopa. Our data demonstrate that levodopa is well-tolerated by children with AS. However, in the doses used in this study, it failed to improve their neurodevelopment or behavioral outcome.


Assuntos
Síndrome de Angelman/tratamento farmacológico , Levodopa/uso terapêutico , Síndrome de Angelman/diagnóstico , Síndrome de Angelman/fisiopatologia , Síndrome de Angelman/psicologia , Animais , Biomarcadores , Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Modelos Animais de Doenças , Humanos , Levodopa/administração & dosagem , Potenciação de Longa Duração , Camundongos , Testes Neuropsicológicos , Resultado do Tratamento
12.
J Appl Res Intellect Disabil ; 31(1): e49-e58, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27990716

RESUMO

BACKGROUND: Angelman syndrome is a rare disorder in which most individuals do not develop speech. Testing of communication ability using traditional neuropsychological measures reveals a performance level at or near the floor of the instrument resulting in an inability to detect change when experimental therapeutics are applied. METHODS: Nine individuals, with molecularly confirmed AS, ranging in age from 34 to 126 months, and a single healthy control child (age 16 months) were audio and video-recorded while interacting with a licensed speech-language pathologist in an attempt to elicit vocalization and non-verbal communication. Thirty-minute audio recordings were transcribed and categorized per the Stark Assessment of Early Vocal Development-Revised and a phonetic inventory was created. Using video recordings, gestures were classified by function, either behavioral regulation or social interaction and further categorized as deictic or representational (i.e., behavioral regulation) and joint attention or shared engagement (i.e., social interaction). RESULTS: The range of vocalizations produced by the children with AS was characteristic of children between 0-6 months and none of the children with AS used advanced forms of vocalizations. The mean frequency of reflexive vocalizations, control of phonation and expansion far exceeded the number of uses of canonical syllables, consistant with the characteristics of children around 12 months of age. Most vocalizations were either laughter or isolated vowels, only three children with AS produced consonant-vowel combinations. Children with AS tended to use central and low vowels with few producing high vowels, suggesting the presence of childhood apraxia of speech. CONCLUSION: Our results show the utilization of video-recorded behavioral observations provides a feasible and reliable alternative for quantification of communication ability in this patient population and may be employed during future clinical studies of potential therapeutics.


Assuntos
Síndrome de Angelman/psicologia , Comunicação , Fala/fisiologia , Criança , Pré-Escolar , Feminino , Gestos , Humanos , Lactente , Masculino
13.
Inf. psiquiátr ; (229): 41-51, jul.-sept. 2017. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-168000

RESUMO

Se presenta la visión de 62 familias españolas que viven con una persona con Síndrome de Angelman. Mayoritariamente son menores de edad con importantes problemas de comunicación, autonomía, control motor y conducta. Reciben mucha más atención profesional en los ámbitos de comunicación y control motor que en los de conducta y autonomía. El desarrollo de modelos de atención en estas dos áreas es prioritaria. La epilepsia y los problemas de sueño también son muy prevalentes y son atendidos en el ámbito sanitario. Según avanzan en edad un mayor porcentaje de niños son escolarizados en centros de educación especial. Más de un tercio de las personas habían sido diagnosticadas con confirmación genética en el primer año y dos tercios antes de los dos años. El asesoramiento tras el diagnóstico es una clara área de mejora


The view of 62 Spanish families that share their lives with someone with Angelman syndrome is presented. They are mostly under 18 and present problems in communication, motor control, behavior and functional independence. They get much more professional help in communication and motor control than in the areas of social behavior and functionality. The development of models of support in these two areas is a priority. Epilepsy and sleep problems are also very prevalent and are dealt with within the health system. The older the children are the higher the probability of receiving education in a special school. More than one third of the sample got genetic diagnosis within the first year of life and more than two thirds within the second. Follow-up and counseling after diagnosis is missing in many cases; in order to provide comprehensive support this needs to be improved


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Síndrome de Angelman/psicologia , Família/psicologia , Síndrome de Angelman/epidemiologia , Comunicação em Saúde/métodos , Fala/fisiologia , Espanha/epidemiologia , Síndrome de Angelman/reabilitação , Inquéritos e Questionários , Análise de Dados/métodos
14.
Res Dev Disabil ; 69: 105-115, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28844022

RESUMO

Angelman syndrome is a rare genetic syndrome, in which sleep disturbances are reported for 20-80% of individuals (Williams et al., 2006). This interview study delineated parental perceptions of sleep problems experienced by children with Angelman syndrome and the impact on parental sleep quality, health and wellbeing. The nature of desired interventions was also explored. Semi-structured interviews were completed with parents of 50 children, aged 16 months-15 years with Angelman syndrome who experienced current or historic sleep problems; predominantly night waking and settling problems. Parents were concerned by the impact of their child's sleep quality upon their own ability to function during the day. The importance of considering parental experiences was evidenced by variability in coping e.g. despite the persistence of sleep problems 20% of parents did not feel the need for any additional support. Amongst a range of types of further support desired, 27% cited further support with a behavioural intervention, and information about the trajectory of sleep problems in Angelman syndrome (18%). The results suggest that behavioural interventions supporting both children and parents in improving their sleep quality and well-being, and longitudinal research into sleep problems should be prioritised.


Assuntos
Síndrome de Angelman , Controle Comportamental/métodos , Efeitos Psicossociais da Doença , Pais/psicologia , Qualidade de Vida , Higiene do Sono , Sonambulismo , Adaptação Psicológica , Adolescente , Adulto , Síndrome de Angelman/psicologia , Síndrome de Angelman/terapia , Criança , Pré-Escolar , Saúde da Família , Feminino , Humanos , Lactente , Masculino , Percepção Social , Sonambulismo/psicologia , Sonambulismo/terapia , Reino Unido
15.
Arch Pediatr ; 24(8): 757-765, 2017 Aug.
Artigo em Francês | MEDLINE | ID: mdl-28668215

RESUMO

Social cognitive impairments may largely contribute to reduced social skills and adaptive problems in individuals with microdeletion syndromes associated with behavioral and psychiatric phenotypes. Understanding the role of social information processing deficits in the emergence of psychotic disorders is a crucial challenge in the management of these patients. Each neurogenetic disorder is characterized by a specific social cognition phenotype. Clarifying the social ability profile of each population may help adjust patient care according to their key strengths and weaknesses. The main objective of this article is to review the social cognitive skills of various neurogenetic disorders and shed light on the specific mechanisms that may underlie these skills in each syndrome. After detailing the different processes unified under the generic term "social cognition", we present these processes in the most frequent microdeletion syndromes presenting with social interaction deficits: 22q11.2 deletion syndrome, Angelman syndrome, fragile X syndrome, Klinefelter syndrome, Prader-Willi syndrome, Rett syndrome, Smith-Magenis syndrome, Turner syndrome, and Williams syndrome. Finally, we highlight future approaches that may have a significant influence on the development of adapted therapeutic interventions, such as cognitive remediation therapies. The importance of connecting neurocognitive and social cognition remediations is also emphasized.


Assuntos
Cognição , Relações Interpessoais , Transtornos Mentais/psicologia , Fenótipo , Síndrome de Angelman/psicologia , Criança , Transtornos Cognitivos/psicologia , Síndrome de DiGeorge/psicologia , Síndrome do Cromossomo X Frágil/psicologia , Humanos , Deficiência Intelectual/psicologia , Síndrome de Klinefelter/psicologia , Transtornos Mentais/diagnóstico , Transtornos Mentais/genética , Transtornos Mentais/terapia , Síndrome de Prader-Willi/psicologia , Síndrome de Rett/psicologia , Síndrome de Smith-Magenis/psicologia , Síndrome de Turner/psicologia , Síndrome de Williams/psicologia
16.
Eur J Pediatr ; 176(2): 225-232, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28000035

RESUMO

Angelman syndrome (AS) is a congenital syndrome with a prevalence of 1:15,000. Individuals with AS often have severe intellectual disability, typical dysmorphic signs, and behavioral problems. The aim of the study was to investigate the rate of incontinence and associated psychological problems in children and adults with AS. Ninety children (4-18 years) and 54 adults (18-31 years) with AS were recruited through a parent support group (55.6% male, mean age 15.1 years). The Parental Questionnaire: Enuresis/Urinary Incontinence, the Incontinence Questionnaire-Pediatric Lower Urinary Tract Symptoms (ICIQ-CLUTS), as well as the Developmental Behaviour Checklist for parents (DBC-P) or for adults (DBC-A) were filled out by parents or caregivers. 85.6% of individuals with AS were affected by at least one subtype of incontinence (82.7% nocturnal enuresis (NE), 64.7% daytime urinary incontinence (DUI), and 57.1% fecal incontinence (FI)). 52.5% of the children and 32.6% of adults reached a clinically relevant DBC score. Incontinence was not associated with behavioral problems. NE and DUI were associated with genotype and epilepsy. CONCLUSION: Children with AS have high rates of incontinence. Many adults are still affected by NE, DUI, or even FI. Screening, assessment, and treatment of incontinence in individuals with AS are recommended. What is Known: • Incontinence in persons with Angelman syndrome (AS) is associated with younger age, lower level of adaptive functioning, and epilepsy. What is New: • Children and teens with AS are at special risk for incontinence, but older persons are also affected. • Comorbid epilepsy is significantly associated not only with nocturnal enuresis (NE) but also with daytime urinary incontinence (DUI). Underlying genotype is significantly associated with incontinence.


Assuntos
Síndrome de Angelman/complicações , Enurese Diurna/epidemiologia , Incontinência Fecal/epidemiologia , Enurese Noturna/epidemiologia , Adolescente , Fatores Etários , Síndrome de Angelman/psicologia , Criança , Pré-Escolar , Enurese Diurna/diagnóstico , Epilepsia/complicações , Epilepsia/epidemiologia , Incontinência Fecal/diagnóstico , Feminino , Humanos , Incidência , Deficiência Intelectual/epidemiologia , Masculino , Enurese Noturna/diagnóstico , Pais , Índice de Gravidade de Doença , Transtornos do Sono-Vigília/epidemiologia , Estatísticas não Paramétricas , Inquéritos e Questionários , Adulto Jovem
17.
Neuropharmacology ; 116: 142-150, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27986596

RESUMO

Angelman syndrome (AS) is a rare neurogenetic disorder characterized by severe developmental delay, motor impairments, and epilepsy. GABAergic dysfunction is believed to contribute to many of the phenotypic deficits seen in AS. We hypothesized that restoration of inhibitory tone mediated by extrasynaptic GABAA receptors could provide therapeutic benefit. Here, we report that ganaxolone, a synthetic neurosteroid that acts as a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors, was anxiolytic, anticonvulsant, and improved motor deficits in the Ube3a-deficient mouse model of AS when administered by implanted mini-pump for 3 days or 4 weeks. Treatment for 4 weeks also led to recovery of spatial working memory and hippocampal synaptic plasticity deficits. This study demonstrates that ganaxolone ameliorates many of the behavioral abnormalities in the adult AS mouse, and tolerance did not occur to the therapeutic effects of the drug. The results support clinical studies to investigate ganaxolone as a symptomatic treatment for AS.


Assuntos
Síndrome de Angelman/tratamento farmacológico , Anticonvulsivantes/farmacologia , Pregnanolona/análogos & derivados , Convulsões/tratamento farmacológico , Síndrome de Angelman/fisiopatologia , Síndrome de Angelman/psicologia , Animais , Ansiolíticos/farmacologia , Ansiedade/tratamento farmacológico , Ansiedade/fisiopatologia , Modelos Animais de Doenças , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/fisiopatologia , Potenciação de Longa Duração/efeitos dos fármacos , Potenciação de Longa Duração/fisiologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Memória de Curto Prazo/efeitos dos fármacos , Memória de Curto Prazo/fisiologia , Camundongos Knockout , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Pentilenotetrazol , Pregnanolona/farmacologia , Receptores de GABA-A/metabolismo , Convulsões/fisiopatologia , Convulsões/psicologia , Memória Espacial/efeitos dos fármacos , Memória Espacial/fisiologia , Técnicas de Cultura de Tecidos , Ubiquitina-Proteína Ligases/deficiência , Ubiquitina-Proteína Ligases/genética
18.
Am J Intellect Dev Disabil ; 121(6): 465-486, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27802104

RESUMO

Few comparative studies have evaluated the heterogeneity of sociability across a range of neurodevelopmental disorders. The Sociability Questionnaire for People with Intellectual Disability (SQID) was completed by caregivers of individuals with Cornelia de Lange (n = 98), Angelman (n = 66), Fragile X (n = 142), Down (n = 117) and Rubinstein Taybi (n = 88) syndromes and autism spectrum disorder (ASD; n = 107). Between groups and age-band (<12yrs; 12-18yrs; >18yrs) comparisons of SQID scores were conducted. Rates of behaviors indicative of selective mutism were also examined. Fragile X syndrome achieved the lowest SQID scores. Cornelia de Lange, ASD, and Fragile X groups scored significantly lower than Angelman, Down and Rubinstein Taybi groups. Selective mutism characteristics were highest in Cornelia de Lange (40%) followed by Fragile X (17.8%) and ASD (18.2%). Age-band differences were identified in Cornelia de Lange and Down syndrome.


Assuntos
Síndrome de Angelman/psicologia , Transtorno do Espectro Autista/psicologia , Síndrome de Lange/psicologia , Síndrome de Down/psicologia , Síndrome do Cromossomo X Frágil/psicologia , Síndrome de Rubinstein-Taybi/psicologia , Habilidades Sociais , Adolescente , Criança , Feminino , Humanos , Masculino , Inquéritos e Questionários
19.
Ital J Pediatr ; 42(1): 91, 2016 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-27769316

RESUMO

BACKGROUND: Angelman Syndrome (AS) is a rare neurodevelopment disorder resulting from deficient expression or function of the maternally inherited allele of UBE3A gene. The aim of the study is to attempt at providing a detailed definition of neurodevelopmental profile in AS, with particular regard to motor, cognitive, communicative, behavioural and neurovisual, features by using standardized instruments. METHOD: A total of ten subjects aged from 5 to 11 years (4 males and 6 females) with molecular confirmed diagnosis of AS (7 15q11.2-q13 deletion and 3 UBE3A mutation) were enrolled in our study. All of them underwent an assessment protocol including neurological and neurovisual examination and the evaluation of motor (Gross Motor Function Measure Scale), cognitive (Griffiths Mental Development Scale and Uzgiris-Hunt Scale); adaptive (Vineland Adaptive Behavioural Scale); communication (MacArthur-Bates Communicative Development Inventory and video-recordings children's verbal expression), behavioural aspects (IPDDAG Scale) and neurovisual aspects. RESULTS: All children presented motor function involvement. A severe cognitive impairment was detected with different profiles according to the test applied. In all cases, communicative disability (phonemic inventory, word/gesture comprehension and production) and symptoms of inattention disorder were revealed. Neurovisual impairment was characterized by refractive errors, fundus oculi anomalies, strabismus and/or oculomotor dysfunction. CONCLUSION: AS presents a complex neurodevelopmental profile in which several aspects play a negative role in global development leading to a severe functional impairment. Intellectual disability is not the only component because neurovisual functions and behavioural disorders may worsen the global function and are needed of specific rehabilitation programs.


Assuntos
Síndrome de Angelman/fisiopatologia , Síndrome de Angelman/psicologia , Criança , Pré-Escolar , Feminino , Humanos , Inteligência , Masculino , Destreza Motora , Testes Neuropsicológicos , Inquéritos e Questionários
20.
Dev Neurorehabil ; 19(5): 315-20, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25549057

RESUMO

OBJECTIVE: This study investigates outcome of scoliosis treatment for 11 children with Angelman syndrome (AS), with particular focus on activity, participation and the musculoskeletal factors that may affect these outcomes. METHODS: Retrospective review of medical records, radiographs and questionnaires administered to caregivers of 11 children (8M:3F) with AS and scoliosis. Six underwent observational treatment during childhood and five underwent spinal fusion. The Activities Scale for Kids (ASKp) questionnaire was used to measure activity and participation. Questionnaire and radiographic data were recorded over a 2 year period. RESULTS: In the observational group, scoliosis increased from 31° to 46°. Mean ASKp decreased from 13.8 to 11.9 (p = 0.06). In the operative group, scoliosis decreased from 68° to 29°. Mean ASKp increased from 11.4 to 15.9 (p < 0.01). There was also a reduction in spinal-related pain and mean number of hospital admissions for chest infection. However, there was a 60% major complication rate. There was no difference in mobility, GMFCS level, feeding or communication in either group before or after treatment. CONCLUSION: In children with significant scoliosis and AS, spinal fusion was associated with a small improvement in activity and participation, reduction in pain and a decrease in frequency of severe chest infections. Non-operative treatment resulted in progression of scoliosis during childhood and decrease in activity.


Assuntos
Síndrome de Angelman/psicologia , Síndrome de Angelman/reabilitação , Escoliose/cirurgia , Fusão Vertebral , Adolescente , Síndrome de Angelman/complicações , Criança , Pré-Escolar , Comunicação , Feminino , Humanos , Lactente , Masculino , Atividade Motora , Destreza Motora , Procedimentos Ortopédicos/efeitos adversos , Procedimentos Ortopédicos/métodos , Dor/etiologia , Dor/reabilitação , Complicações Pós-Operatórias/epidemiologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/etiologia , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Inquéritos e Questionários , Resultado do Tratamento
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