Transición de jóvenes con trastornos del neurodesarrollo / The transition of youth with neurodevelopmental disorders

La transición de la atención pediátrica a la de adultos, en adolescentes y jóvenes con condiciones crónicas de salud, es un proceso necesario y difícil. El proceso de transición de estos pacientes contará con diferentes matices según la condición de salud, las características del sistema sanitario, los equipos de salud involucrados y los factores contextuales del joven y su familia. El objetivo central es que a través de una autonomía progresiva el joven llegue a ser un adulto competente en cuanto a asumir y manejar sus necesidades de salud, relaciones sociales y laborales que su enfermedad crónica le permita. Pero estos objetivos se ven interferidos cuando hablamos de jóvenes con condiciones crónicas que involucran el neurodesarrollo y es más complejo aún cuando nos referimos a jóvenes que no serán autónomos. Para las familias y cuidadores de estos jóvenes los centros pediátricos son un entorno más protegido que cuesta dejar. Por todo esto es que, si bien hay lineamientos generales a tener en cuenta, cada equipo debe revisar sus resultados para poder avanzar. Aún no se logró consenso acerca de cuál es el momento óptimo, la edad y las mejores estrategias, aunque es reconocida la dificultad para implementar un programa adecuado y más aún evaluar los resultados de los programas que se utilizan en la transición; se llevan adelante programas "genéricos" utilizados para diferentes enfermedades crónicas, o específicos para una enfermedad, otros programas combinan ambas estrategias. Basados en lo anterior hay jóvenes y familias que requieren un armado "artesanal y a medida" (AU)

The transition from pediatric to adult care for adolescents and young people with chronic health conditions is a necessary yet challenging process. This transition will vary depending on the health condition, the characteristics of the health system, the health teams involved, and the contextual factors of the youth and their family. The central objective is for the youth to achieve progressive autonomy, becoming a competent adult capable of managing their health needs, social, and work relationships, as allowed by their chronic disease. However, these objectives become more complicated when dealing with young people with chronic conditions involving neurodevelopment, and even more so for those who will never achieve autonomy. For the families and caregivers of these youths, pediatric centers offer a more protected environment that is difficult to leave. For all these reasons, while general guidelines should be considered, each team must review its results to move forward. Consensus has not yet been reached on the optimal time, age, and best strategies for transition. It is recognized that implementing an adequate program is challenging, and evaluating the results of these programs is even more difficult. There are "generic" programs used for various chronic diseases, as well as disease-specific programs, and some programs combine both strategies. Given these complexities, some young people and their families require a "handcrafted and tailor-made" approach (AU)

Correlation of early neurodevelopmental features of children with SYNGAP1 variants and their genotypes / 中华医学遗传学杂志

OBJECTIVE@#To explore the early neurodevelopmental features of young children with SYNGAP1 variants and their genotype-phenotype correlation.@*METHODS@#Young children with neurodevelopmental disorders (NDDs) (< 5 years old) who were referred to the Children's Hospital Affiliated to the Capital Institute of Pediatrics between January 2019 and July 2022 were selected as the study subjects. All children had undergone whole-exome sequencing, comprehensive pediatric neuropsychological assessment, familial segregation analysis, and pathogenicity classification. Meanwhile, young Chinese NDD children (< 5 years old) with pathogenic/likely pathogenic SYNGAP1 variants were retrieved from the literature, with information including detailed clinical and genetic testing, neurodevelopmental quotient (DQ) of the Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016). Children who did not have a detailed DQ but had their developmental status assessed by a medical professional were also included. The correlation between neurodevelopmental severity, comorbidity and SYNGAP1 variants were summarized.@*RESULTS@#Four young NDD children carrying SYNGAP1 variants were recruited (1 male and 3 females, with a mean age of 34.0 ± 18.2 months), among whom one harboring a novel variant (c.437C>G, p.S146*). Combined with 19 similar cases retrieved from the literature, 23 Chinese NDD young children were included in our study (8 males and 10 females, 5 with unknown sex, with a mean age of 37.1 ± 14.2 months). A loss of function (LOF) variant was found in 19 (82.6%) children. All of the children had presented global developmental delay (GDD) before the age of two. In addition, 16 (69.6%) had seizure/epilepsy at the age of 27.0 ± 12.1 months, among whom 15 had occurred independent of the global developmental delay. Myoclonic and absence were common types of seizures. Compared with those with variants of exons 8 to 15, the severity of developmental delay was milder among children with variants in exons 1 to 5.@*CONCLUSION@#The early neurodevelopment features of the SYNGAP1 variants for young children (< 5 years old) have included global developmental delay and seizure/epilepsy. All of the children may present GDD before the age of two. The severity of developmental delay may be related to the type and location of the SYNGAP1 variants.

Analysis of a child with neurodevelopmental disorders due to variant of HNRNPU gene and a literature review / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic variant in a child with neurodevelopmental disorders (NDDs).@*METHODS@#Clinical data of a child who had presented at Xiaogan Hospital Affiliated to Wuhan University of Science and Technology in December 2020 due to intermittent convulsions for over a year were retrospectively analyzed. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. "HNRNPU gene", "epilepsy", "epileptic encephalopathy", "hereditary epilepsy", "neurodevelopmental disorder", "neurodevelopmental syndrome", "HNRNPU", and "NDDs" were used as the key words to search the CNKI, Wanfang and PubMed databases dated from January 1, 1994 to February 10, 2022.@*RESULTS@#The patient was a 2-year-old boy who had developed seizure at the age of 5 months. His clinical features had included abnormal appearance, recurrent seizures, and low developmental quotients of each functional area as evaluated by the Gesell scale. The child was given sodium valproate for the antiepileptic treatment and rehabilitation training. He had become seizure-free within half a year of follow-up, but his intelligence and motor development did not improve significantly. Genetic testing revealed that he has harbored a heterozygous c.1720_1722delCTT (p.Lys574del) variant of the HNRNPU gene, which was not found in either of his parents. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic (PS2+PM2_Supporting+PM4). A total of 13 articles were retrieved, and the types of HNRNPU gene mutations have included splice site mutation, nonsense mutation, missense mutation, in-frame deletion, gene duplication, frameshifting mutation, and multiple exon deletion. The main clinical manifestations have included mental retardation, language delay, global developmental delay, epilepsy, craniofacial deformity, mental and behavioral abnormalities.@*CONCLUSION@#The c.1720_1722delCTT variant of the HNRNPU gene probably underlay the NDDs in this child. Above finding has enriched the mutational spectrum of the HNRNPU gene.

Perfil de atos comunicativos de crianças com transtorno do desenvolvimento de linguagem / Profile of communicative acts of children with developmental language disorder

RESUMO Objetivo Caracterizar os atos comunicativos de crianças com transtorno do desenvolvimento da linguagem, verificando a quantidade de atos comunicativos, atos comunicativos interativos e sua relação com a idade cronológica. Métodos Foram participantes 40 crianças de ambos os gêneros com diagnóstico de transtorno do desenvolvimento da linguagem com idades entre 3 anos e 2 meses e 7 anos e 11 meses. Todos os sujeitos foram avaliados com a Prova de Pragmática ABFW - Teste de Linguagem Infantil, em sua avaliação inicial. Especificamente para este estudo, focou-se na verificação da quantidade de atos comunicativos, atos comunicativos por minuto, atos comunicativos interativos e número de iniciativas comunicativas. Resultados Os dados indicaram que crianças com transtorno do desenvolvimento da linguagem apresentam alterações importantes em relação aos atos comunicativos e interações comunicativas e há correlação dessas variáveis com a idade cronológica. Conclusão Crianças com transtorno do desenvolvimento da linguagem apresentam diminuição no número de atos comunicativos, atos comunicativos interativos e interações comunicativas, quando comparadas aos valores de referência de crianças típicas, independentemente da idade.

ABSTRACT Purpose To characterize the communicative acts of children with Developmental Language Disorder, verifying the number of communicative acts, interactive communicative acts, and their relationship with chronological age. Methods Forty children of both sexes with a diagnosis of Developmental Language Disorder aged between 3 years and seven years and 11 months were subjects. All subjects were assessed with the ABFW Pragmatics Test - Child Language Test in their initial assessment. Specifically, this study focused on verifying the number of communicative acts, communicative acts per minute, interactive communicative acts, and the number of communicative initiatives. Results The data indicate that children with Developmental Language Disorder present significant alterations concerning communicative acts and communicative interactions, and there is a correlation between these variables and chronological age. Conclusion Children with Developmental Language Disorder show a decrease in the number of communicative acts, interactive communicative acts, and communicative interactions when compared to the reference values of typical children, regardless of age.

Impacto de la pandemia: acceso a la salud y la educación de los pacientes atendidos en 2019 y 2020 en Policlínica de Neurodesarrollo del Servicio de Neuropediatría del CHPR / Impact of the pandemic on the health and education of patients who received assistance at the Pereira Rossell Pediatric Hospital's Neurodevelopment Clinic in 2019 and 2020 / Impacto da pandemia: acesso à saúde e educação para pacientes atendidos durante os anos 2019 e 2020 na Policlínica de Neurodesenvolvimento do Serviço de Neuropediatria do CHPR

La pandemia ha repercutido en los hábitos cotidianos y en la salud de las personas en múltiples formas, afectando el acceso a las consultas médicas, tratamientos especializados y educación. Las poblaciones con mayor vulnerabilidad socioeconómica o de salud, o ambas, parten de un lugar más desfavorecido respecto a otras ante una situación de pandemia. En el marco de la situación sanitaria de emergencia, realizamos un estudio con el fin de conocer el perfil de desarrollo de los niños atendidos en la Policlínica de Neurodesarrollo del Servicio de Neuropediatría del CHPR durante 2020 y comparar el acceso a servicios de salud y educación con el de aquellos atendidos en 2019, por medio de un estudio descriptivo longitudinal. La información fue relevada mediante entrevista telefónica con los referentes y el análisis de los informes de la evaluación del desarrollo realizada. Según los resultados obtenidos se constata un menor acceso a la educación y a la salud en tiempos de pandemia y repercusiones variadas en la vida cotidiana de los niños con trastornos del neurodesarrollo, manifestando los referentes 60% de impacto negativo, principalmente en el aumento de la irritabilidad y la inquietud. Las restricciones de la pandemia han puesto en primer plano las consecuencias de problemáticas que existían previamente, como ser el costoso acceso a tratamientos especializados y dificultades en el acceso a la educación de calidad adaptada al perfil de desarrollo de cada niño. Esperamos, con el presente trabajo, aportar en mejorar las condiciones ambientales y el acceso a oportunidades de los niños pequeños con patologías del desarrollo.

The pandemic has impacted people's daily habits and health in multiple ways, affecting access to medical consultations, specialized treatments, and education. Populations with greater socioeconomic and/or health vulnerability start from a more disadvantaged level in a pandemic situation. Within the framework of the emergency health situation, we carried out a longitudinal descriptive study in order to know the development profile of the children assisted at the CHPR Clinic in 2020 and compared their access to health and education services to those assisted in 2019. The data was collected through a telephone interview with the referents and the data analyses were obtained from the development assessment reports carried out. The results showed that there is less access to education and health in pandemic times and there are various impacts on the daily life of children with neurodevelopmental disorders. Referents showed a 60% negative impact, mainly in the increase in irritability and restlessness. The pandemic restrictions brought on the consequences of previously existing problems, such as expensive access to specialized treatments and difficulty to access quality education adapted to the development profile of individual children. This paper intends to contribute to the improvement of the environmental conditions and access to opportunities of young children with developmental pathologies.

A pandemia teve impacto nos hábitos diários e na saúde das pessoas de múltiplas formas, afetando o acesso a consultas médicas, tratamentos especializados e educação. As populações com maior vulnerabilidade socioeconómica e/ou sanitária partem dum nível mais desfavorecido quando confrontados com a situação pandêmica. No âmbito da situação de emergência sanitária, realizamos um estudo descritivo longitudinal com o objetivo de conhecer o perfil de desenvolvimento das crianças atendidas na referida Policlínica durante o ano de 2020 e comparar o acesso aos serviços de saúde e educação com o das crianças atendidas no ano de 2019. As informações foram coletadas através de entrevistas telefônicas com os referentes e da análise dos relatórios da avaliação de desenvolvimento realizada. De acordo com os resultados obtidos, há menor acesso à educação e à saúde em tempos de pandemia e existem repercussões variadas no quotidiano das crianças com perturbações do neurodesenvolvimento. Os referentes reportaram um impacto negativo de 60%, principalmente no aumento da irritabilidade e da inquietação. As restrições da pandemia trouxeram as consequências de problemas anteriormente existentes, como o acesso dispendioso a tratamentos especializados e as dificuldades de acesso a uma educação de qualidade e adaptada ao perfil de desenvolvimento de cada criança. Esperamos com este trabalho contribuir para a melhoria das condições ambientais e do acesso a oportunidades para crianças pequenas com patologias de desenvolvimento.

Redes sociais significativas maternas: significados e movimentos diante do autismo / Maternal significant social networks: meanings and movements in the face of autism / Redes sociales significativas maternas: significados y movimientos frente al autismo

O diagnóstico de uma condição crônica na família tende a movimentar as relações intra e extrafamiliares. No caso do Transtorno do Espectro do Autismo (TEA), essa movimentação tende a ocorrer de forma significativa com os vínculos maternos, visto que as mães costumam ser as principais cuidadoras dos filhos com esse diagnóstico. Assim, o presente estudo objetivou investigar os impactos do diagnóstico de TEA nas redes sociais significativas maternas e como as mães lhes atribuíram sentido. Participaram 12 mães de filhos diagnosticados com TEA na infância, com as quais foram realizadas entrevistas reflexivas e construídos dois mapas de redes sociais significativas, um anterior e outro posterior ao TEA. A análise dos dados foi feita através da Grounded Theory . No momento inicial da entrevista, foi possível perceber que a maioria das participantes se referiu ao sentimento de não ter apoio, expressando desamparo. Todavia, ao longo do processo de construção dos mapas, percebeu-se relevante mudança no discurso das mães, que reconheceram e se surpreenderam com a presença de vínculos importantes nas suas redes sociais, embora, da sua perspectiva, eles não lhes proporcionem o apoio necessário. Portanto, destaca-se a importância da ativação das redes sociais significativas das mães, bem como a instrumentalização dessas redes para que possam estar presentes de maneira efetiva e fornecer apoio, salientando-se o importante papel de profissionais da saúde e da educação nesse cenário. Por fim, aponta-se o mapa de redes enquanto potente instrumento clínico e de pesquisa.(AU)

The diagnosis of a chronic condition in the family tends to move intra- and extra-family relationships. In the Autistic Spectrum Disorder (ASD) case, this movement tends to occur significantly with maternal bonds, since mothers are often referred as the main caregivers of children with this diagnosis. Thus, this study aimed to investigate the impacts of the ASD diagnosis on significant maternal social networks and how mothers signify these implications. Twelve mothers of children diagnosed with ASD in childhood participated, with whom reflective interviews were carried out and two maps of significant social networks, one before and one after the ASD, were constructed. Data analysis was performed by using Grounded Theory. At the beginning of the interview, it was possible to observe that most participants reported the feeling of having no support, expressing helplessness. However, throughout the mapping process, a relevant change was noticed in the mothers' discourse, who recognized and were surprised by the presence of important members in their social networks, although, in their perspective, they do not provide them the necessary support. Therefore, the importance of activating the mothers' significant social networks is highlighted, as well as the instrumentalization of these networks so that they can be effectively present and provide support, emphasizing the important role of health and education professionals in this scenario. Finally, the network map is pointed out as a powerful clinical and research tool.(AU)

El diagnóstico de una enfermedad crónica en la familia tiende a trasformar las relaciones intra y extrafamiliares. En el caso del trastorno del espectro del autismo (TEA), este movimiento tiende a ocurrir de manera significativa con los vínculos maternos, ya que las madres son referidas como las principales cuidadoras de los niños con este diagnóstico. Este estudio tuvo por objetivo investigar el impacto del diagnóstico de TEA en las redes sociales maternas significativas y cómo las madres dieron sentido a estas implicaciones. Participaron en este estudio doce madres de niños diagnosticados con TEA en la infancia, y se utilizaron entrevistas reflexivas y mapas de redes sociales significativas, uno para antes y otro para después del TEA. El análisis de datos se basó en la teoría fundamentada. Al inicio de la entrevista, la mayoría de las participantes refirieron sentir que no tenían apoyo. Sin embargo, en el proceso de construcción de los mapas se vio un cambio en el discurso de las madres, quienes comenzaron a reconocer y sorprenderse por la presencia de vínculos importantes en sus redes sociales, aunque estos no les brindaran el apoyo necesario. Se resalta la importancia de activar las redes sociales significativas de las madres, así como la instrumentalización de estas redes para que puedan estar efectivamente presentes y brindar apoyo, enfatizando el papel de los profesionales de la salud y la educación. Además, se señala el mapa de la red como una poderosa herramienta clínica e investigativa.(AU)

Desarrollo infantil y sus principales desafíos en los primeros años de vida: lugar e importancia de los centros de educación y protección del Instituto del Niño y Adolescente del Uruguay / Child development and its main challenges in the first years of life: place and importance of the education and protection centers of the Children and Adolescents Institute of Uruguay

Existe un aumento progresivo de los problemas del neuropsicodesarrollo. Las intervenciones psicoeducativas y sociales oportunas con soporte en evidencias mejoran la evolución a lo largo de la vida de los niños. Los Centros Educativos en Primera Infancia tienen el potencial de identificar precozmente a niños con riesgos de alteraciones en el neuropsicodesarrollo. El Centro de Formación y Estudios del Instituto del Niño y Adolescente del Uruguay convoca a la Unidad Académica de Psiquiatría Pediátrica para la formación y actualización en esta problemática. El objetivo del trabajo es implementar un Programa de Capacitación en desarrollo normal, sus variaciones y desafíos; oportunidades de estimulación, identificación precoz de alteraciones e intervenciones en Centros Educativos en Primera Infancia; simultáneamente capacitar en habilidades de comunicación y trabajo interdisciplinario a posgrados de psiquiatría pediátrica y otras disciplinas de salud mental. Está dirigido a trabajadores del Instituto del Niño y Adolescente del Uruguay que trabajan con niños de 0 a 3 años. La implementación se realiza a través de tres modalidades articuladas, escalando progresivamente en contenidos: 1) Conferencias abiertas. 2) Curso introductorio a través de talleres virtuales sincrónicos. 3) Instancias docentes de profundización con equipos de Centros Educativos en Primera Infancia. Resultados: 2800 inscriptos. Se realizaron dos conferencias (4500 participantes en total), ocho cursos introductorios y se está implementando la modalidad 3 para el año 2024. Las encuestas de satisfacción han sido entre muy buenas-excelente. Se concluye que la implementación de este Programa de Capacitación permite la difusión de conocimientos y el intercambio interdisciplinario, por lo que es necesario continuar la cooperación entre Unidades Académicas, explorar otras modalidades pedagógicas y estudiar el impacto de la capacitación.

A progressive increase in neuro-psycho- developmental problems has taken place; timely evidence-based psycho-educational and social interventions improve children's lifelong development. Early Childhood Educational Centers have the potential for early identification of children at risk for neurodevelopmental disorders. The Training and Studies Center of the Institute of Childhood and Adolescence of Uruguay convenes the Academic Unit of Pediatric Psychiatry for training and updating on this issue. The objective is to implement a Training Program on normal development, its variations and challenges; stimulation opportunities, early identification of changes and interventions in Early Childhood Educational Centers, while training pediatric psychiatry postgraduates and other mental health disciplines in communication skills and interdisciplinary work. Methodology: Aimed at workers of the Institute of Childhood and Adolescence of Uruguay, working with children from 0 to 3 years old. Three articulated modalities, progressively increasing in content: 1) Open lectures. 2) Introductory course: synchronous virtual workshops. 3) Teaching instances with teams from Early Childhood Educational Centers. Results: 2800 participants. Two conferences (4500 participants) and eight introductory courses were held. Modality 3 is being organized for 2024. Satisfaction surveys show very good to excellent results. It is concluded that the implementation of this training Program makes knowledge dissemination and interdisciplinary exchange possible, so it is necessary to continue cooperation between academic units, explore other pedagogical modalities and study training impact.

Notas sobre lo pre-lúdico y lo lúdico en psicoanálisis: el caso Agustín / Notes sur le pré-ludiqueet le ludiqueen psychanalyse: le cas Agustín / Notes on the pre-playand the playfulin psychoanalysis: the Agustín case / Notas sobre o pré-lúdicoe o lúdicoempsicanálise: o caso Agustín

En este artículo se abordan algunas nociones psicoanalíticas que resultan fundamentales al momento de trabajar con niños que presentan patologías graves. Desde la lectura de un caso clínico, se pretende distinguir conceptualmente entre las actividades pre-lúdicas y el juego propiamente dicho. A partir de tales consideraciones, se esbozan ciertas notas en torno al diagnóstico y la orientación del tratamiento, delimitando las diferentes funciones que puede cumplir el juego en el análisis de niños AU

Cet article aborde quelques notions psychanalytiques fondamentales lorsqu'on travaille avec des enfants présentant des pathologies graves. A partir de la lecture d'un cas clinique, il s'agit de distinguer conceptuellement les activités pré-jeu et le jeu lui-même. Sur la base de ces considérations, certaines notes sont esquissées concernant le diagnostic et l'orientation du traitement, délimitant les différentes fonctions que le jeu peut remplir dans l'analyse des enfants AU

This article addresses some psychoanalytic notions that are fundamental when working with children who present serious pathologies. From the reading of a clinical case, it is intended to conceptually distinguish between pre-play activities and the play itself. Based on such considerations, certain notes are outlined around the diagnosis and treatment orientation, delimiting the different functions that play can fulfill in the analysis of children AU

Este artigo aborda algumas noções psicanalíticas que são fundamentais no momento de trabalhar com crianças que apresentam patologias graves. Desde a leitura de um caso clínico, pretende-se distinguir conceptualmente entre as atividades pré-lúdicas e o jogo propriamente dito. A partir de tais considerações, traçam-se certas notas em torno do diagnóstico e da orientação do tratamento, delimitando as diferentes funções que pode cumprir o jogo na análise de crianças AU

Mercurio y trastornos del neurodesarrollo en niños: una revisión sistemática / Mercury and neurodevelopmental disorders in children: A systematic review

El mercurio es un metal tóxico que puede atravesar la placenta y la barrera hematoencefálica, y causar la interrupción de varios procesos celulares. Estudios han investigado la exposición al mercurio y trastornos en el neurodesarrollo, por lo que se requiere un análisis crítico y riguroso de esta evidencia. El objetivo de esta revisión fue evaluar la evidencia científica disponible sobre los efectos de la exposición al mercurio durante las etapas prenatal y posnatal, y su relación con el desarrollo de trastornos neuroconductuales. Se realizó una búsqueda sistemática en las bases de datos MEDLINE y ScienceDirect; los resultados se presentaron a través de tablas y síntesis narrativa. Solo 31 estudios cumplieron los criterios de elegibilidad. En general, la evidencia es limitada sobre los efectos de la exposición al mercurio y trastornos del neurodesarrollo en niños. Entre los posibles efectos reportados, se hallan problemas en el aprendizaje, autismo y trastorno por déficit de atención e hiperactividad.

Mercury is a toxic metal which can cross the placenta and the blood-brain barrier and cause the disruption of various cellular processes. Studies have investigated mercury exposure and neurodevelopmental disorders; therefore, a critical and rigorous analysis of this evidence is required. The objective of this review was to evaluate the available scientific evidence on the effects of mercury exposure during the prenatal and postnatal periods and its relationship with the development of neurobehavioral disorders. A systematic search of the MEDLINE and ScienceDirect databases was conducted; the results were presented in tables and narrative synthesis. Only 31 studies met the eligibility criteria. Overall, the evidence on the effects of mercury exposure and neurodevelopmental disorders in children is limited. Learning disabilities, autism, and attention deficit hyperactivity disorder were some of the reported potential effects.

Las funciones ejecutivas: su significado y aplicación clínica / Executive functions: meaning and clinical application

Las funciones ejecutivas generalmente se conceptualizan como un conjunto de procesos generales de control de orden superior que trabajan juntos para dirigir y gestionar las funciones cognitivas, emocionales y conductuales, especialmente durante la resolución activa de problemas. Su disfunción es frecuente de ser detectada como comorbilidad de otros trastornos del neurodesarrollo, causa o efecto? La detección precoz de la disfunción ejecutiva y su abordaje terapéutico temprano, mejora el pronóstico global madurativo en el periodo infantojuvenil. Esta sucinta revisión de las funciones ejecutivas intenta resaltar su importancia para el pediatra y su mirada de los trastornos del neurodesarrollo (AU)

Executive functions are typically understood as a set of general higher-order control processes that collectively direct and manage cognitive, emotional, and behavioral functions, especially during active problem solving. Their dysfunction is often detected as a comorbidity of other neurodevelopmental disorders; cause or effect? Early detection of executive dysfunction and a prompt therapeutic approach improves the overall developmental prognosis in childhood and adolescence. This brief review of executive functions aims to highlight their importance for the pediatrician and his/her view of neurodevelopmental disorder (AU)

Intervenciones parentales para el desarrollo lingüístico- comunicativo en preescolares con Trastornos del Neurodesarrollo: una revisión sistemática / Parental interventions for linguistic-communicative development in preschoolers with Neurodevelopmental Disorders: a systematic review

Resumen En el actual escenario sociosanitario enfrentado a raíz de la pandemia por SARS-CoV-2, múltiples actividades se han visto mermadas, e incluso, suspendidas por los largos periodos de aislamiento social y las medidas de cuidado para evitar contagios. En este sentido, muchas personas han dejado de recibir con la misma regularidad, o bajo las mismas circunstancias, sus tratamientos, incluyendo a niños con Trastornos del Neurodesarrollo (TND). Es así como surgen las intervenciones Parentales. Estas son programas donde los padres o cuidadores primarios son entrenados para llevar a cabo acciones terapéuticas con el niño y cuyo objetivo puede estar orientado a promover múltiples habilidades. El objetivo de la presente revisión sistemática fue determinar el efecto de estas intervenciones para promover el lenguaje y la comunicación en niños con diagnóstico de TND de entre 2 y 5 años. Se realizó una búsqueda sistemática en las bases de datos ERIC, MEDLINE y PubMed, considerando publicaciones de entre enero del 2010 y marzo de 2022. De las 9885 referencias iniciales, y posterior a las etapas de tamizaje y elegibilidad, 5 fuentes primarias cumplieron con los criterios de selección. Los resultados indican que las intervenciones parentales para habilidades de comunicación serían efectivas e incluso se mantendrían los efectos en medidas de seguimiento. En cuanto a las habilidades de lenguaje, los resultados a través de los estudios son contradictorios. Por otra parte, ninguno de los estudios reporta efectos adversos para los niños. En cuanto a efectos beneficios o adversos para padres o cuidadores primarios, ninguno de los estudios incluidos reporta medidas asociadas.

Abstract In the current socio-sanitary scenario that we are facing as a result of the SARS-CoV-2 Pandemic, there have been many activities that have been reduced and even suspended due to long periods of social isolation and care measures to avoid contagion. In this sense, many people have stopped receiving their treatments with the same regularity or under the same circumstances, including children with Neurodevelopmental Disorders. This is how parental interventions correspond to programs where parents or primary caregivers are trained to carry out therapeutic actions with the child and whose objective may be aimed at promoting multiple skills. The objective of this systematic review was to determine the effect of these interventions to promote language and communication in children diagnosed with Neurodevelopmental Disorders between 2 and 5 years of age. A systematic search was carried out in the ERIC, MEDLINE and PubMed databases including publications between January 2010 and March 2022. Of the 9885 initial references, and after the screening and eligibility stages, 5 primary sources met the selection criteria. The results indicate that parental interventions for communication skills would be effective, and the effects would even be maintained in follow-up measures. Regarding language skills, the results across studies are contradictory. On the other hand, none of the studies reported adverse effects for children. Regarding beneficial or adverse effects for parents or primary caregivers, none of the included studies reported associated measures.

Prediction of Perinatal and Neurodevelopmental Outcomes in Newborns with a Birth Weight below the 3rd Percentile: Performance of Two International Curves - Prospective Cohort from a Brazilian City / Predição de resultados perinatais e de neurodesenvolvimento em recém-nascidos com peso ao nascer abaixo do percentil 3: Desempenho de duas curvas internacionais - coorte prospectiva de uma cidade brasileira

Abstract Objectives To evaluate the performance of Intergrowth-21 st (INT) and Fetal Medicine Foundation (FMF) curves in predicting perinatal and neurodevelopmental outcomes in newborns weighing below the 3rd percentile. Methods Pregnant women with a single fetus aged less than 20 weeks from a general population in non-hospital health units were included. Their children were evaluated at birth and in the second or third years of life. Newborns (NB) had their weight percentiles calculated for both curves. Sensitivity, specificity, positive (PPV) and negative predictive value (NPV), and area under the ROC curve (ROC-AUC) for perinatal outcomes and neurodevelopmental delay were calculated using birth weight < 3rd percentile as the cutoff. Results A total of 967 children were evaluated. Gestational age at birth was 39.3 (± 3.6) weeks and birth weight was 3,215.0 (± 588.0) g. INT and FMF classified 19 (2.4%) and 49 (5.7%) newborns below the 3rd percentile, respectively. The prevalence of preterm birth, tracheal intubation >24 hours in the first three months of life, 5th minute Apgar <7, admission to a neonatal care unit (NICU admission), cesarean section rate, and the neurodevelopmental delay was 9.3%, 3.3%, 1.3%, 5.9%, 38.9%, and 7.3% respectively. In general, the 3rd percentile of both curves showed low sensitivity and PPV and high specificity and NPV. The 3rd percentile of FMF showed superior sensitivity for preterm birth, NICU admission, and cesarean section rate. INT was more specific for all outcomes and presented a higher PPV for the neurodevelopmental delay. However, except for a slight difference in the prediction of preterm birth in favor of INT, the ROC curves showed no differences in the prediction of perinatal and neurodevelopmental outcomes. Conclusion Birth weight below the 3rd percentile according to INT or FMF alone was insufficient for a good diagnostic performance of perinatal and neurodevelopmental outcomes. The analyzes performed could not show that one curve is better than the other in our population. INT may have an advantage in resource contingency scenarios as it discriminates fewer NB below the 3rd percentile without increasing adverse outcomes.

Resumo Objetivos Avaliar o desempenho das curvas de Intergrowth-21 st (INT) e Fetal Medicine Foundation (FMF) na predição de resultados perinatais e de neurodesenvolvimento de recém-nascidos com peso abaixo do percentil 3. Métodos Foram incluídas gestantes de feto único com idade inferior a 20 semanas de uma população geral em unidades de saúde não hospitalares. Seus filhos foram avaliados ao nascimento e no segundo ou terceiro anos de vida. Os recém-nascidos tiveram seus percentis de peso calculados para ambas as curvas. Sensibilidade, especificidade, valor preditivo positivo (VPP) e negativo (VPN) e área sob a curva ROC (ROC-AUC) foram calculados para desfechos perinatais e atraso de neurodesenvolvimento considerando o peso ao nascimento menor que o percentil 3 como ponto de corte. Resultados Um total de 967 crianças foram avaliadas ao nascimento e no segundo ou terceiro anos de vida. A idade gestacional ao nascer foi de 39,3 (±3,6) semanas e o peso ao nascimento foi de 3.215,0 (±588,0) g. INT e FMF classificaram 19 (2,4%) e49 (5,7%) recém-nascidos abaixo do percentil 3, respectivamente. A prevalência de parto prétermo, intubação traqueal > 24 horas nos primeiros três meses de vida, Apgar de 5° minuto < 7, internação em unidade de terapia intensiva neonatal (internação em UTIN), taxa de cesariana e atraso de neurodesenvolvimento foi 9,3%, 3,3%, 1,3%, 5,9%, 38,9% e 7,3% respectivamente. Em geral, o percentil 3 de ambas as curvas apresentou baixa sensibilidade e VPP e alta especificidade e VPN. O percentil 3 de FMF mostrou sensibilidade superior para parto prematuro, internação em UTIN e taxa de cesariana. INT foi mais específico para todos os desfechos e apresentou maior VPP para o atraso do neurodesenvolvimento. Entretanto, exceto por uma pequena diferença na predição de parto pré-termo em favor de INT, as curvas ROC não mostraram diferenças na predição de resultados perinatais e de desenvolvimento neurológico. Conclusão O peso ao nascer abaixo do percentil 3 segundo INT ou FMF isoladamente foi insuficiente para um bom desempenho diagnóstico de desfechos perinatais e de neurodesenvolvimento. As análises realizadas não puderam mostrar que uma curva é melhor que a outra em nossa população. INT pode ter vantagem em cenários de contingência de recursos, pois discrimina menos recém-nascidos abaixo do percentil 3 sem aumentar os desfechos adversos.

Consultas de demanda espontánea sobre trastornos del desarrollo en el Hospital Garrahan / Spontaneous consultations for developmental disorders at Garrahan Hospital

Introducción: Los trastornos del desarrollo (TD) constituyen un motivo de consulta muy frecuente en la práctica pediátrica. El Hospital Garrahan recibe por demanda espontánea al servicio de Mediano Riesgo (MR) consultas de cuidadores con preocupaciones sobre el desarrollo de los niños, niñas y adolescentes (NNyA). Allí son valorados por pediatras clínicos, quienes realizan la interconsulta al servicio de Clínicas Interdisciplinarias del Neurodesarrollo (CIND) según necesidad (representan el 10% del total de consultas en MR). El objetivo del trabajo es comparar las características de los pacientes de MR que fueron consultados al área de Maduración de CIND durante el bimestre marzo/abril de 2016, 2021 y 2022. Materiales y métodos: estudio retrospectivo, observacional y comparativo. Se revisaron las historias clínicas analizando las siguientes variables: edad, procedencia, contar con pediatra de cabecera, cobertura de salud, motivo de consulta y sospecha diagnóstica. Resultados: La cantidad de consultas aumentó por encima del 20%, con un descenso en la mediana de edad de alrededor de un año. Aproximadamente el 70% de los pacientes procedían del conurbano en los tres períodos. Observamos un descenso respecto al número de NNyA con seguimiento pediátrico y cobertura social. El lenguaje y la conducta fueron los motivos más frecuentes de consulta y la mayor sospecha diagnóstica fue el Trastorno del Espectro Autista (TEA). Conclusiones: Los datos observados pueden relacionarse con el impacto de la pandemia así como también con las condiciones socio-económicas de los últimos cinco años, con un mayor conocimiento acerca del desarrollo y un probable aumento de la prevalencia de los TD (AU)

Introduction: Developmental disorders (DD) are a frequent reason for consultation in pediatric practice. The Garrahan Hospital receives spontaneous consultations at the department of Intermediate Risk (IR) from caregivers with concerns about the development of children and adolescents. At the IR department, children and adolescents are evaluated by clinical pediatricians, who consult with specialists at the Interdisciplinary Neurodevelopmental Clinic (INDC) as needed (accounting for 10% of the total number of consultations at the IR department). The aim of this study was to compare the characteristics of IR patients who were consulted at the INDC during the bimonthly period March/April 2016, 2021, and 2022. Materials and methods: a retrospective, observational, and comparative study was conducted. Medical records were reviewed analyzing the following variables: age, provenance, having a primary care pediatrician, healthcare insurance, reason for consultation, and diagnostic suspicion. Results: The number of consultations increased by over 20%, with a decrease in median age of around one year. Approximately 70% of the patients came from Greater Buenos Aires in the three periods. A decrease in the number of children and adolescents with pediatric follow-up and a social health insurance was observed. Language and behavior disorders were the most frequent reasons for consultation and autism spectrum disorder (ASD) was most often suspected. Conclusions: The observed data may be related to the impact of the pandemic as well as socio-economic conditions over the last five years, together with increased knowledge about development and a probable increase in the prevalence of ASD (AU)

Comparación del desempeño de dos pruebas para la evaluación del neurodesarrollo infantil en un hospital pediátrico de la Ciudad Autónoma de Buenos Aires / Comparison of the performance of two tests for the assessment of child neurodevelopment in a children's hospital in the City of Buenos Aires

Introducción. La detección precoz de los trastornos del desarrollo permite aplicar acciones que mejoren su evolución y pronóstico. En nuestro país, la Prueba Nacional de Pesquisa (PRUNAPE) requiere de un profesional certificado. El Instrumento de Observación del Desarrollo Infantil (IODI) es una herramienta de vigilancia sistematizada del desarrollo que no requiere especialización para su aplicación. La utilización del IODI como herramienta de evaluación del neurodesarrollo sería de utilidad por su fácil aplicabilidad. Objetivo. Evaluar el desempeño del IODI como prueba de vigilancia de trastornos del desarrollo utilizando la PRUNAPE como patrón de oro. Población y métodos. Estudio prospectivo analítico de prueba diagnóstica. Se incluyeron de forma aleatoria pacientes de 1 mes a 4 años, cuyos padres dieron el consentimiento para participar. Se evaluó el desempeño del IODI usando la PRUNAPE como patrón de oro. Se estimaron los valores de clivaje de sensibilidad (S), especificidad (E), valores predictivos positivo y negativo (VPP y VPN), y las razones de verosimilitud positiva y negativa (RVP y RVN, respectivamente). Resultados. Se evaluaron 91 pacientes; 24 no pasaron la PRUNAPE, de los cuales 21 tampoco pasaron el IODI (sensibilidad: 87,5 %; especificidad: 79,1 %; valor predictivo positivo: 60,1 %; valor predictivo negativo: 94,6 %). Razón de verosimilitud positiva: 4,2; negativa: 0,2. Conclusión. El IODI mostró un desempeño aceptable como prueba de vigilancia de trastornos del desarrollo en comparación con la PRUNAPE.

Introduction. An early detection of developmental disorders allows to implement actions to improve their course and prognosis. In Argentina, the administration of the National Screening Test (Prueba Nacional de Pesquisa, PRUNAPE) requires a certified professional. The Child Development Observation Instrument (Instrumento de Observación del Desarrollo Infantil, IODI) is a systematized developmental surveillance tool that does not require specialization for its administration. The use of the IODI as a neurodevelopmental assessment tool would be useful because of its easy applicability. Objective. To assess the performance of the IODI as a surveillance test for developmental disorders using the PRUNAPE as a gold standard. Population and methods. Analytical, prospective study with a diagnostic test. Patients aged 1 month to 4 years, whose parents gave consent to participate, were included randomly. The IODI performance was assessed using the PRUNAPE as the gold standard. Sensitivity (S), specificity (Sp), positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratios (PLR and NLR) were estimated. Results. Ninety-one patients were assessed; 24 failed the PRUNAPE, of these, 21 also failed the IODI (S: 87.5%, Sp: 79.1%, PPV: 60.1%, NPV: 94.6%). PLR: 4.2, NLR: 0.2. Conclusion. The IODI showed an acceptable performance as a developmental disorders surveillance test compared to the PRUNAPE.

Depression and anxiety among caregivers of children and adolescents with neurodevelopmental disorders in a government tertiary hospital during the Covid-19 pandemic

Objectives@#To determine the burden of COVID-19 related mental health problems such as anxiety and/or depression among caregivers of children and adolescents with neurodevelopmental disorders in a government tertiary hospital.@*Materials and Methods@#This is a cross-sectional study conducted at the Out-patient Department of PCMC. Caregiver data sheet and HADS-P forms were given to eligible caregivers.@*Results@#A total of 102 caregivers were included. The prevalence of significant risk for anxiety disorder among caregivers of children and adolescents with neurodevelopmental disorders is 34.31% (n=35), 1.96% (n=2) for depression and 3.92% (n=4) for both anxiety and depression. Using logistic regression, marital status of common law partner and female sex have significant association with depression and anxiety; the number of household members has a direct association to significant risk for both anxiety and depression.@*Conclusion@#Female sex and common law partnership as marital status are associated with 2-3 times of having significant risk for anxiety or depression. The number of household members is correlated with an increased significant risk of having both anxiety and depression. Screening caregivers using appropriate tests would identify caregivers at significant risk for anxiety and depression and further create intervention programs.

Analysis of NOVA2 gene variant in a child with Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child with Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities (NEDASB).@*METHODS@#A child with NEDASB who presented at the Third Affiliated Hospital of Zhengzhou University in July 2021 was selected as the subject. Peripheral blood samples of the child and her parents were collected and subjected to high-throughput sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child was found to harbor a heterozygous c.820_828delinsCTTCA (p.Thr274Leufs*121) variant of the NOVA2 gene, for which both of her parents were of wild type. The variant was predicted as pathogenic based on the guidelines from the American College of Medical Genetics and Genomics.@*CONCLUSION@#The heterozygous c.820_828delinsCTTCA (p.Thr274Leufs*121) variant of the NOVA2 gene probably underlay the disease in this child. Above finding has enriched the spectrum of NOVA2 gene variants and provided a basis for genetic counseling and prenatal diagnosis for this family.

Genetic background of idiopathic neurodevelopmental delay patients with significant brain deviation volume / 中华医学杂志(英文版)

BACKGROUND@#Significant brain volume deviation is an essential phenotype in children with neurodevelopmental delay (NDD), but its genetic basis has not been fully characterized. This study attempted to analyze the genetic factors associated with significant whole-brain deviation volume (WBDV).@*METHODS@#We established a reference curve based on 4222 subjects ranging in age from the first postnatal day to 18 years. We recruited only NDD patients without acquired etiologies or positive genetic results. Cranial magnetic resonance imaging (MRI) and clinical exome sequencing (2742 genes) data were acquired. A genetic burden test was performed, and the results were compared between patients with and without significant WBDV. Literature review analyses and BrainSpan analysis based on the human brain developmental transcriptome were performed to detect the potential role of genetic risk factors in human brain development.@*RESULTS@#We recruited a total of 253 NDD patients. Among them, 26 had significantly decreased WBDV (<-2 standard deviations [SDs]), and 14 had significantly increased WBDV (>+2 SDs). NDD patients with significant WBDV had higher rates of motor development delay (49.8% [106/213] vs . 75.0% [30/40], P  = 0.003) than patients without significant WBDV. Genetic burden analyses found 30 genes with an increased allele frequency of rare variants in patients with significant WBDV. Analyses of the literature further demonstrated that these genes were not randomly identified: burden genes were more related to the brain development than background genes ( P  = 1.656e -9 ). In seven human brain regions related to motor development, we observed burden genes had higher expression before 37-week gestational age than postnatal stages. Functional analyses found that burden genes were enriched in embryonic brain development, with positive regulation of synaptic growth at the neuromuscular junction, positive regulation of deoxyribonucleic acid templated transcription, and response to hormone, and these genes were shown to be expressed in neural progenitors. Based on single cell sequencing analyses, we found TUBB2B gene had elevated expression levels in neural progenitor cells, interneuron, and excitatory neuron and SOX15 had high expression in interneuron and excitatory neuron.@*CONCLUSION@#Idiopathic NDD patients with significant brain volume changes detected by MRI had an increased prevalence of motor development delay, which could be explained by the genetic differences characterized herein.

Genetic analysis of a child with early onset neurodevelopmental disorder with involuntary movement and a literature review / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical phenotype and genetic basis of a child with early onset neurodevelopmental disorder with involuntary movement (NEDIM).@*METHODS@#A child who presented at Department of Neurology of Hunan Children's Hospital on October 8, 2020 was selected as the study subject. Clinical data of the child were collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents. Whole exome sequencing (WES) was carried out for the child. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. Relevant literature was searched from the CNKI, PubMed and Google Scholar databases to summarize the clinical phenotypes and genetic variants of the patients.@*RESULTS@#This child was a 3-year-and-3-month boy with involuntary trembling of limbs and motor and language delay. WES revealed that the child has harbored a c.626G>A (p.Arg209His) variant of the GNAO1 gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. The variant had been reported in HGMD and ClinVar databases, but not in the dbSNP, ExAC and 1000 Genomes databases. Prediction with SIFT, PolyPhen-2, and Mutation Taster online software suggested that the variant may be deleterious to the protein function. By UniProt database analysis, the encode amino acid is highly conserved among various species. Prediction with Modeller and PyMOL software indicated that the variant may affect the function of GαO protein. Based on the guideline of the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic.@*CONCLUSION@#The GNAO1 gene c.626G>A (p.Arg209His) variant probably underlay the NEDIM in this child. Above finding has expanded the phenotypic spectrum of GNAO1 gene c.626G>A (p.Arg209His) variant and provided a reference for clinical diagnosis and genetic counseling.

Recent research on neurodevelopmental disorders in children / 中国当代儿科杂志

Neurodevelopmental disorders (NDDs) in children are a group of chronic developmental brain disorders caused by multiple genetic or acquired causes, including disorders of intellectual development, developmental speech or language disorders, autism spectrum disorders, developmental learning disorders, attention deficit hyperactivity disorder, tic disorders, and other neurodevelopmental disorders. With the improvement in the research level and the diagnosis and treatment techniques of NDDs, great progress has been made in the research on NDDs in children. This article reviews the research advances in NDDs, in order to further improve the breadth and depth of the understanding of NDDs in children among pediatricians.

Autosomal dominant neurodevelopmental disorders associated with KIF1A gene variants in 6 pediatric patients / 浙江大学学报·医学版

OBJECTIVES@#To analyze the clinical and genetic characteristics of children with autosomal dominant neurodevelopmental disorders caused by kinesin family member 1A (KIF1A) gene variation.@*METHODS@#Clinical and genetic testing data of 6 children with KIF1A gene de novo heterozygous variation diagnosed in Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine from the year 2018 to 2020 were retrospectively analyzed. Pathogenic variants were identified based on whole exome sequencing, and verified by Sanger sequencing. Moreover, the effect of variants on three-dimensional structure and stability of protein was analyzed by bioinformatics.@*RESULTS@#Among 6 patients there were 4 males and 2 females, and the age of consultation varied from 7 months to 18 years. All cases had varying degrees of motor developmental delay since childhood, and 4 of them had gait abnormalities or fell easily. In addition, 2 children were accompanied by delayed mental development, epilepsy and abnormal eye development. Genetic tests showed that all 6 cases had heterozygous de novo variations of KIF1A gene, including 4 missense mutations c.296C>T (p.T99M), c.761G>A (p.R254Q), c.326G>T (p.G109V), c.745C>G (p.L249V) and one splicing mutation c.798+1G>A, among which the last three variants have not been previously reported. Bioinformatics analysis showed that G109V and L249V may impair their interaction with the neighboring amino acid residues, thereby impacting protein function and reducing protein stability, and were assessed as "likely pathogenic". Meanwhile, c.798+1G>A may damage an alpha helix in the motor domain of the KIF1A protein, and was assessed as "likely pathogenic".@*CONCLUSIONS@#KIF1A-associated neurological diseases are clinically heterogeneous, with motor developmental delay and abnormal gait often being the most common clinical features. The clinical symptoms in T99M carriers are more severe, while those in R254Q carriers are relatively mild.