Language, neurodevelopment, and behavior in Angelman syndrome: a case report. / Linguagem, neurodesenvolvimento e comportamento na Síndrome de Angelman: relato de caso.

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.

OBJETIVO: O objetivo deste estudo é apresentar achados de linguagem, comportamento e neurodesenvolvimento de uma menina com diagnóstico da Síndrome de Angelman, avaliada aos três e aos oito anos. MÉTODO: Os instrumentos de avaliação foram Observação do Comportamento Comunicativo, Early Language Milestone Scale (ELM) e Teste de Screening de Desenvolvimento DENVER-II (TSDD-II). RESULTADOS: No caso apresentado, verifica-se a presença dos sinais fenotípicos da SA, tais como boca larga, dentes espaçados, língua protuberante, estrabismo, fissuras palpebrais ascendentes e sialorreia. Na avaliação de linguagem, foram verificados déficits expressivos e receptivos, com ausência de oralidade e prejuízos na compreensão. O TSDD-II e a ELMS indicaram grave comprometimento de todas as habilidades avaliadas aos três e aos oito anos. O desempenho encontrado, nas duas avaliações, foi muito semelhante em todas as áreas do desenvolvimento infantil. Ao longo dos anos, verificou-se pouca evolução, apesar do grande investimento terapêutico e educacional. CONCLUSÃO: A presença de um quadro complexo como a SA demanda necessidades clínicas de alta complexidade, situação agravada frente à escassez de recursos terapêuticos que possam minimizar os impactos deletérios da síndrome, culminando em comprometimento da qualidade de vida da população com a SA, bem como de suas famílias.

Spaced training improves learning in Ts65Dn and Ube3a mouse models of intellectual disabilities.

Benefits of distributed learning strategies have been extensively described in the human literature, but minimally investigated in intellectual disability syndromes. We tested the hypothesis that training trials spaced apart in time could improve learning in two distinct genetic mouse models of neurodevelopmental disorders characterized by intellectual impairments. As compared to training with massed trials, spaced training significantly improved learning in both the Ts65Dn trisomy mouse model of Down syndrome and the maternally inherited Ube3a mutant mouse model of Angelman syndrome. Spacing the training trials at 1 h intervals accelerated acquisition of three cognitive tasks by Ts65Dn mice: (1) object location memory, (2) novel object recognition, (3) water maze spatial learning. Further, (4) spaced training improved water maze spatial learning by Ube3a mice. In contrast, (5) cerebellar-mediated rotarod motor learning was not improved by spaced training. Corroborations in three assays, conducted in two model systems, replicated within and across two laboratories, confirm the strength of the findings. Our results indicate strong translational relevance of a behavioral intervention strategy for improving the standard of care in treating the learning difficulties that are characteristic and clinically intractable features of many neurodevelopmental disorders.

Linguagem, neurodesenvolvimento e comportamento na Síndrome de Angelman: relato de caso / Language, neurodevelopment, and behavior in Angelman syndrome: a case report

RESUMO Objetivo O objetivo deste estudo é apresentar achados de linguagem, comportamento e neurodesenvolvimento de uma menina com diagnóstico da Síndrome de Angelman, avaliada aos três e aos oito anos. Método Os instrumentos de avaliação foram Observação do Comportamento Comunicativo, Early Language Milestone Scale (ELM) e Teste de Screening de Desenvolvimento DENVER-II (TSDD-II). Resultados No caso apresentado, verifica-se a presença dos sinais fenotípicos da SA, tais como boca larga, dentes espaçados, língua protuberante, estrabismo, fissuras palpebrais ascendentes e sialorreia. Na avaliação de linguagem, foram verificados déficits expressivos e receptivos, com ausência de oralidade e prejuízos na compreensão. O TSDD-II e a ELMS indicaram grave comprometimento de todas as habilidades avaliadas aos três e aos oito anos. O desempenho encontrado, nas duas avaliações, foi muito semelhante em todas as áreas do desenvolvimento infantil. Ao longo dos anos, verificou-se pouca evolução, apesar do grande investimento terapêutico e educacional. Conclusão A presença de um quadro complexo como a SA demanda necessidades clínicas de alta complexidade, situação agravada frente à escassez de recursos terapêuticos que possam minimizar os impactos deletérios da síndrome, culminando em comprometimento da qualidade de vida da população com a SA, bem como de suas famílias.

ABSTRACT 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.

El Síndrome de Angelman en España: la visión de las familias / No disponible

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

Exploring Expressive Communication Skills in a Cross-Sectional Sample of Children and Young Adults With Angelman Syndrome.

PURPOSE: This study explores data on expressive communication skills of 300 individuals aged 0.0-21.11 years with Angelman syndrome (AS). These data provide a composite portrait of communication skills in a large sample of children and young adults with this rare disorder, specifying new detailed information about expressive communication. METHOD: The database associated with the Communication Matrix assessment (Rowland, 2004, 2011; Rowland & Fried-Oken, 2010) was mined for data regarding individuals with AS. We extracted data on the reasons for communicating, level of communication achieved, and use of various expressive communication modes to convey 24 specific messages. The performance of children and young adults in 5 age groups in the cross-sectional sample were contrasted. RESULTS: Results confirmed earlier studies showing that few individuals with AS use natural speech. However, in addition to using presymbolic modes, many children used alternative symbolic modes such as picture symbols, object symbols, and manual signs. Assessment scores increased slightly with age, F(4, 295) = 2.416, p = .049. CONCLUSIONS: Aggregating data on a large sample of individuals with AS provides a reference point for practitioners and family members and a basis for future investigations.

"Over time it just becomes easier ": parents of people with Angelman syndrome and Prader-Willi syndrome speak about their carer role.

PURPOSE: This study investigated two of the stresses experienced by parents caring for offspring with Angelman syndrome (AS) and Prader-Willi syndrome (PWS) in Western Australia, and identified their coping strategies. METHODS: Parents of 19 offspring with AS and PWS participated in the Family Stress and Coping Interview which provides a stress level score, and a discussion of stressors and coping methods associated with 24 life situations, two of which are reported. All text was examined using directed content analysis. RESULTS: Family carers (14/19) reported high stress associated with the initial diagnosis of AS or PWS in their offspring; and finding time for themselves. Stressors identified included lack of quality information about the disorder, time constraints and physical and emotional tiredness. Parents adopted a variety of coping strategies, including learning about the disorder, accepting the situation, seeking instrumental and social supports and dealing with problems. CONCLUSIONS: No specific coping strategy was associated with reduced stress. However, parents felt that accurate and timely information during the diagnostic period helped. Parents used family and community support although there were difficulties accessing respite care. It is advised that government agencies, service providers, family members and peer support associations should provide practical and emotional support to assist the parents of offspring with AS and PWS, and indeed any form of intellectual disability, across the lifespan. Implications for Rehabilitation Long-term caring for offspring with AS or PWS can involve considerable stress for parents. Stress has been associated with poorer health outcomes for parental carers. Parents need a variety of practical and emotional supports to cope with stress, including timely access to information.

A retrospective review to assess whether spinal fusion and scoliosis correction improved activity and participation for children with Angelman syndrome.

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.

Teaching discriminated social approaches to individuals with Angelman syndrome.

Angelman syndrome is a neurogenetic disorder characterized by intellectual and developmental disability. Common behavioral characteristics of this disorder include a heightened interest in social interactions and frequent bids to initiate interaction. These bids can be problematic, for instance, when a child attempts to hug strangers in public places. The current study evaluated a discrimination training program to teach 3 boys with Angelman syndrome to discriminate appropriate from inappropriate times to initiate interactions. During baseline, we alternated periods in which attention was delivered following social initiations on a continuous reinforcement schedule with periods in which initiations were placed on extinction. We then implemented discrimination training by presenting a salient discriminative stimulus, prompting the occurrence of initiations, and providing reinforcement during reinforcement periods and withdrawing the stimulus during extinction periods. This resulted in discriminated approaches for each of the 3 participants; these results were replicated across caregivers and extended to the participants' homes.

Parents' perceptions of communication patterns and effectiveness of use of augmentative and alternative communication systems by their children with Angelman syndrome.

PURPOSE: The author describes communication patterns and outcomes of augmentative and alternative communication (AAC) intervention for individuals with Angelman syndrome. METHOD: Parents self-administered a web-based survey using Qualtrics software. A series of rating scales and closed questions were used to gather information about individuals' current methods of communication, including AAC devices they were using. Individuals' uses of their single most advanced AAC devices were further explored in terms of associated importance, usefulness, success, acceptance, and functional outcomes. RESULTS: Nonsymbolic methods of communication proved to be very important to individuals, as did electronic AAC devices, although to a lesser extent. Individuals tended to have access to more than one electronic device concurrently. Although numerous devices were cited, mobile technologies, particularly iPads, were especially prevalent. This represented a significant change from a previous investigation. Overall, device use was perceived to be frequently important, accepted, successful, and useful in relation to 8 different factors, although ratings across a series of 19 functional outcomes varied. Differences were noted on several measures when individuals' ages and educational placements were considered. CONCLUSION: Results suggest a changing landscape in terms of types of devices used, particularly with respect to mobile technologies, and show clear evidence that device use is often, although not uniformly, associated with positive outcomes.

Toilet training in individuals with Angelman syndrome: a case series.

OBJECTIVE: To assess if adapted versions of the response restriction toilet training protocol, based on the behavioral phenotype of Angelman syndrome (AS), were successful in fostering urinary continence in seven individuals with AS. METHOD: Data were collected in AB-designs during baseline, training, generalization and follow-up. The response restriction protocol was adapted: individuals were trained in their natural environment, were prompted to void and along with improving continence, the interval between voids was prolonged and time-on-toilet decreased. RESULTS: During generalization five individuals had less than two accidents and one to six correct voids per day; during baseline more accidents and/or less correct voids occurred. In two participants correct voids increased, but several accidents still occurred. Three participants maintained positive results after 3-18 months. CONCLUSION: Despite their intellectual and behavioral challenges, urinary continence can be acquired in AS. Several indications of voiding dysfunctions were found; further research is indicated.

Parents' reports of patterns of use and exposure to practices associated with AAC acceptance by individuals with Angelman syndrome.

Abstract The primary purpose of this investigation was to enhance our understanding of AAC use by individuals with Angelman syndrome (AS) in relation to two broad genotypes: Deletion Positive (DP) and Non Deletion (ND). Previous investigators have suggested individuals without deletions typically exhibit stronger cognitive and communicative abilities than their DP counterparts. This investigation focused on several aspects of AAC use: communication systems used; exposure to, success with, and acceptance of electronic AAC devices; and exposure to practices associated with AAC acceptance. Results indicated that both groups rely heavily on unaided, nonsymbolic methods of communication, with the ND group more likely to use conventional, symbolic systems. While the two groups were similar with respect to exposure to an array of electronic devices, the DP group appeared more likely to have gone no further than low-tech devices such as the BIGmack™. There was strong evidence of both groups' capabilities for success with high-tech devices and overall acceptance of devices in terms of duration of use. This proved especially noteworthy in light of both groups' limited exposure to practices associated with AAC acceptance. Clinical implications of these findings are discussed along with future avenues of research.

Proposta de atuação fisioterapêutica em uma criança com síndrome de Angelman, enfatizando o equilíbrio postural: estudo de caso / Proposal for a physical therapy program in a child with Angelman syndrome, emphasizing postural balance: a case study / Propuesta de actuación fisioterapéutica en un niño con Síndrome de Angelman, enfatizando el equilibrio postural: estudio de caso

A síndrome de Angelman (SA) é caracterizada por alterações neuromotoras como marcha atáxica e atraso na aquisição de habilidades motoras, porém são escassos os estudos investigando o efeito de intervenções aplicadas a essa população. O objetivo do estudo foi verificar o efeito de um treino de equilíbrio em uma criança com SA. Participou do estudo uma criança de nove anos de idade com diagnóstico de SA, sexo feminino. Foi aplicado um protocolo para treino de equilíbrio por oito semanas, com frequência de duas vezes por semana. O treino consistiu em atividades envolvendo equilíbrio estático sob diversas condições de dificuldade. Após o treino, a análise de biofotogrametria computadorizada do equilíbrio estático revelou redução do grau de oscilação, que passou de 38° para 13,78°. A pontuação na escala de Berg passou de 27 pontos, na avaliação, para 37 pontos na reavaliação. No teste Timed Up & Go, a criança realizou a tarefa em 15 segundos, na avaliação, e, na reavaliação, em 12 segundos. Em conjunto, os resultados sugerem que o treino favoreceu melhora no equilíbrio estático e dinâmico, bem como na mobilidade funcional.

The Angelman syndrome is characterized by neuromotor difficulties, such as ataxic gait and delayed acquisition of motor skills. However, there are few studies investigating the effect of interventions directed to this population. This study aimed to investigate the effect of a balance training in a child with Angelman syndrome. The participant was a nine-year-old girl. The training protocol was implemented during an eight-week period, twice a week, and consisted of activities involving static balance under various difficulty levels. After the training, the postural sway measured by biophotogrammetry changed from 38° to 13.78°. The scores in the Berg scale changed from 27 points to 37 points. In the Timed Up & Go test, the child's time to complete the task changed from 15 to 12 seconds. Taken together, the results suggest that the training led to improved static and dynamic balance, as well as functional mobility.

El síndrome de Angelman (SA) es caracterizado por alteraciones neuromotoras como marcha atáxica y atraso en la adquisición de habilidades motoras, pero son escasos los estudios investigando el efecto de intervenciones aplicadas a esta población. El objetivo de este estudio fue verificar el efecto de un entrenamiento del equilibrio en un niño con SA. Participó del estudio un niño de 9 años de edad con diagnóstico de SA, sexo femenino. Fue aplicado un protocolo de entrenamiento para el equilibrio por 8 semanas, con frecuencia de 2 veces por semana. El entrenamiento consistió en actividades involucrando el equilibrio estático sobre diversas condiciones de dificultad. Después del entrenamiento el análisis de biofotogrametría computarizada del equilibrio estático reveló reducción de los grados de oscilación, que pasó de 38° para 13,78°. La puntuación en la escala de Berg pasó de 27 puntos en la evaluación para 37 puntos en la reevaluación. En el test Timed up and go la niña realizó la tarea en 15 segundos en la evaluación y 12 segundos en la reevaluación. En conjunto, los resultados sugieren que el entrenamiento favoreció la mejora en el equilibrio estático y dinámico, así como de la movilidad funcional.

Neurodevelopmental outcomes in children with Angelman syndrome after 1 year of behavioural intervention.

OBJECTIVE: To examine the impact of teaching approaches based on the principles of applied behaviour analysis (ABA) on neurodevelopmental outcomes in children with Angelman syndrome (AS). METHODS: A non-randomized pre-test-post-test control group design was used. The intervention group consisted of four children with AS aged 3.1-9.2 years. Controls were other children with AS who were individually matched on the basis of chronological age, gender and molecular sub-type. Children in the intervention group were provided two-to-three ABA-based therapy sessions per week over a 1-year period. Standardized measures of cognitive, adaptive and language functioning were administered at baseline and after 1 year. RESULTS: There were no statistically significant differences between the two groups at baseline or after 1 year. However, positive trends were observed in the intervention group for some cognitive and adaptive measures. CONCLUSION: ABA-based intervention improved aspects of neurodevelopment for some children with AS and warrants further study.

Functional analysis and functional communication training in individuals with Angelman syndrome.

OBJECTIVE: To assess the functions of challenging behaviour in four children with Angelman syndrome (AS) and to study the effects of functional communication training (FCT) with precursor-based prompting. This study builds on and extends the study of Allen et al. METHOD: Experimental functional analysis assessed behavioural functions. FCT was implemented within an ABAB design and effect sizes were calculated. Burst analyses depict tendencies in (precursor) behaviours surrounding target behaviours. RESULTS: Results show challenging behaviour to be aimed at receiving attention, tangibles or escape. Burst analysis designated physical and eye contact and reaching for tangibles as precursors. Effects of FCT ranged from small to large. CONCLUSION: Behavioural functions for challenging behaviour were found and FCT was effective in reducing its frequency, when precursors were used as the onset of prompting. Functional equivalence between challenging and communicative behaviour was found. Implementing treatment for challenging behaviour based on precursors is advised.

Parents' priorities for AAC and related instruction for their children with Angelman Syndrome.

This investigation examined the extent to which a set of 98 best practices in AAC, previously agreed upon by a panel of experts in AAC and inclusive education, reflected the actual preferences of 32 parents of children diagnosed with Angelman Syndrome. Parents' responses were examined in relation to whether their children were currently in mostly integrated (MI) settings with children without disabilities, or mostly segregated settings with other children with disabilities. With two exceptions, both groups, regardless of their children's current placements, viewed the practices favorably. When asked to prioritize the most important communication skills they wished their children to attain, all of the most frequently cited priorities were reflected in items contained in the questionnaire, supporting the social validity of the questionnaire as truly reflecting parents' priorities for AAC instruction. Implications of this investigation are discussed, along with next steps.

Functioning and disability in patients with Angelman syndrome: utility of the International Classification of functioning disability and health, children and youth adaptation framework.

PURPOSE: Angelman syndrome (AS) accounts for upto 6% of all cases with severe mental retardation and epilepsy. Clinical findings include developmental delay, severely impaired expressive language, ataxic gait, tremulousness of limbs and a typical behavioral profile including a happy demeanour, hyperactive behavior and low attention span. Seizures, abnormal electroencephalogram, microcephaly and scoliosis are observed in >80% of patients. Cognitive, language and orthopedic problems must be addressed with vigorous rehabilitation programs. Classification of functioning disability and health, children and youth adaptation (ICF-CY) can provide the most adequate framework to describe the condition of the persons towards whom rehabilitative efforts are concentrated. The aim of the study is to test whether the ICF-CY framework is effectively able to capture the various dimensions of health in AS. METHODS: We applied the ICF-CY, to the detail of second level codes, to a cohort of 11 patients with AS of various ages. The coding was obtained by the multi-professional team following these children for the rehabilitation program. RESULTS: The functional profile obtained applying the ICF-CY is complete and comparable with the characteristics of the syndrome described in literature. The possibility of highlighting not only the problems but also the points of strength appears as very helpful. The second level codes may be too broad to provide insight in the clinical and rehabilitative peculiarities, and the use of the full power of the classification may be more advisable for clinical use. CONCLUSIONS: This prelimiary study shows that ICF-CY is a valid tool to frame the clinical characteristics of a complex syndrome as AS, and may give a strong foundation for the rehabilitation programming.