Aspectos neurobiológicos del Síndrome de Rett

El Síndrome de Rett es un trastorno monogénico ligado al cromosoma X, de carácter progresivo que afecta el neurodesarrollo principalmente de niñas durante las primeras etapas del ciclo vital. Su etiología se debe principalmente a las mutaciones de cambio de nucleótido único con pérdida de función del gen MECP2. Este gen codifica para la proteína del mismo nombre cuya principal función es actuar como un represor global de la transcripción mediante el reconocimiento de zonas metiladas de islas CpG y el reclutamiento de factores correpresores que modulan la expresión génica desacetilando histonas. Dentro de las principales alteraciones estructurales asociadas al síndrome se encuentran una morfología neuronal atípica con tamaño del soma neuronal y número de espinas dendríticas reducido, además de alteraciones neuroquímicas sobre todo en la señalización GABAérgica llevando a una desregulación entre señales excitatorias e inhibitorias, causando epilepsia. También se han descrito una serie de alteraciones metabólicas, oxidativas e inflamatorias. El tratamiento hasta ahora se ha enfocado más en buscar un alivio sintomático para las manifestaciones del síndrome pero se ha desarrollado recientemente terapia génica con el objetivo de tratar desde sus bases neurogenéticas la patología y evitar así el desarrollo alterado durante la niñez.

Rett Syndrome is a monogenic disorder linked to the X chromosome, of a progressive nature that affects neurodevelopment mainly in girls during the first stages of the life cycle. Its etiology is mainly due to loss-of-function single nucleotide change mutations of the MECP2 gene. This gene codes for the protein of the same name whose main function is to act as a global repressor of transcription through the recognition of methylated areas of CpG islands and the recruitment of corepressor factors that modulate gene expression by deacetylating histones. Among the main structural alterations associated with the syndrome are an atypical neuronal morphology with a size of the neuronal soma and a reduced number of dendritic spines, in addition to neurochemical alterations, especially in the GABAergic signal, leading to dysregulation between excitatory and inhibitory signals, causing epilepsy. A series of metabolic, oxidative, and inflammatory disorders have also been described. Until now, treatment has focused more on seeking symptomatic relief for the manifestations of the syndrome, but gene therapy has recently been developed with the aim of treating the pathology from its neurogenetic bases and thus avoiding altered development during childhood.

Mecanismos epigenéticos involucrados en la génesis del autismo / Epigenetic mechanisms involved in the genesis of autism

Resumen El autismo es un trastorno del neurodesarrollo de base neurobiológica, caracterizado por alteración en la interacción social y la comunicación, intereses restringidos y conductas estereotipadas. Se relaciona con trastornos en la sinaptogénesis y a multiples etiologías. La identificación de factores epigenéticos implicados en la génesis del autismo permiten una mejor comprensión de los mecanismos moleculares invo lucrados. Nuestro objetivo fue analizar los mecanismos epigenéticos relacionados al desarrollo del autismo, puntualizando entidades específicas y sus mecanismos fisiopatológicos. Analizamos de qué manera se rela cionan los trastornos en la metilación del ADN, la modificación de las histonas, la remodelación cromosómica y la regulación mediada por el ARN no codificantes con diversos síndromes genéticos como el frágil X, Rett, Mecp2patías, Phelam McDermid, tóxicos prenatales como el alcohol, ácido valproico, cannabis y ambientales cómo el estrés materno, todos ellos asociados a una mayor prevalencia de autismo. En conclusión, el recono cimiento de estos mecanismos abre nuevas posibilidades para la prevención, y probablemente en un futuro, en las entidades genéticas, permitirá el desarrollo de tratamientos específicos con modificaciones a la medida de cada entidad.

Abstract Autism is a neurobiological developmental disorder characterized by poor social interaction and communication, narrow interests, and stereotyped behaviors. It has been associated with disorders of synaptogenesis and multiple etiologies. The iden tification of the epigenetic factors involved in the genesis of autism allows a better understanding of the molecular mechanisms involved. Our objective was to analyze the epigenetic mechanisms related to the development of autism, specifying specific entities and their pathophysiological mechanisms. We analyze how DNA methylation disorders, histone modification, remodeling and chromosomal regulation mediated by non-coding RNA are related to various genetic syndromes such as fragile X, Rett, Pathias Mecp2, Phelam McDermid, prenatal toxins such as alcohol, valproic. acid, cannabis, and environmental toxins such as maternal stress, all associated with a higher prevalence of autism. In conclusion: the recognition of these mechanisms opens up new possibilities for preven tion and it is likely that, in genetic entities, it will allow the development of specific treatments with modifications tailored to each entity.

Síndrome de Rett: reporte de una nueva variante patogénica y revisión de la literatura a propósito de dos casos clínicos / Rett syndrome: report of a new pathogenic variant and review of the literature regarding two clinical cases

Resumen Introducción: El síndrome de Rett es un trastorno del neurodesarrollo con una frecuencia estimada de 1/10,000 recién nacidos vivos, el cual se presenta con un modelo de herencia ligado al cromosoma X. Las variantes patogénicas en el gen MECP2, el cual codifica para una proteína que participa en el desarrollo y la diferenciación del sistema nervioso central, causan este síndrome. El objetivo de este trabajo fue describir dos casos de síndrome de Rett, uno de ellos con una nueva variante del gen MECP2. Casos clínicos: El primer caso se trata de una paciente de 5 años con microcefalia y regresión del neurodesarrollo desde los 3 años. Clínicamente se diagnosticó de síndrome de Rett en estadio III. Se realizó la secuenciación del gen MECP2 y se identificó una variante probablemente patogénica en estado heterocigoto, c.606delC (p.Thr203Argfs*7), que no ha sido reportada previamente. El segundo caso es una paciente de 17 años, referida por discapacidad intelectual grave, que se encontró clínicamente en estadio IV. Se realizó la secuenciación de MECP2 y se identificó una variante patogénica [c.880C>T(p.Arg294*)] ya descrita previamente. Conclusiones: El diagnóstico clínico de síndrome de Rett se llevó a cabo con criterios establecidos. La confirmación diagnóstica fue mediante la secuenciación de MECP2. Para el correcto abordaje de los trastornos del neurodesarrollo es primordial conocer el fenotipo de síndrome de Rett, así como optar por el análisis molecular para la confirmación del diagnóstico. Los pacientes con síndrome de Rett requieren un seguimiento interdisciplinario para disminuir el impacto de las complicaciones.

Abstract Background: Rett syndrome is an X-linked neurodevelopmental disorder with an estimated frequency of 1/10,000 live births caused by hetereozygous pathogenic variants in the MECP2 gene, whose protein participates in the development and differentiation of the central nervous system. This study aimed to describe two cases with Rett syndrome diagnosis, one of them with a new variant of the MECP2 gene. Case reports: We first describe the case of a 5-year-old female with microcephaly and neurodevelopmental regression starting at 3 years old, clinically corresponding to stage III Rett syndrome. Sequencing of the MECP2 gene identified a heterozygous likely pathogenic variant [c.606delC (p.Thr203Argfs*7)] not reported previously. The second case is a 17-year-old female, referred due to severe intellectual disability, clinically found on stage IV. MECP2 sequencing was performed identifying a pathogenic variant previously described [c.880C> T (p.Arg294 *)]. Conclusions: Rett syndrome clinical diagnosis was carried out based on established criteria. MECP2 sequencing confirmed the diagnosis. For neurodevelopmental disorders approach, it is essential to know the phenotype of Rett syndrome and select the molecular tool for the diagnosis. Patients with Rett syndrome require interdisciplinary follow-up for reducing the impact of complications.

Manejo e integración estomatológica del paciente pediátrico con trastorno de Asperger / Management and dental integration of the pediatric patient with Asperger disorder

Trastorno neurológico enmarcado dentro de los trastornos de espectro autista (TEA) cuyas manifestaciones se reflejan en los ámbitos de la comunicación, interacción e imaginación social. Se clasifica en el manual diagnóstico y estadístico de trastornos mentales (DSM IV), se caracteriza por un mayor o menor grado de deterioro en las habilidades de lenguaje y comunicación, así como patrones repetitivos o restrictivos de pensamiento y comportamiento. El síntoma más distintivo es el interés obsesivo en un solo objeto o tema y la exclusión de cualquier otro pero siempre conservando habilidades de lenguaje. El pronóstico es bueno, debido a la compensación cognitiva, el enfoque repetitivo y restrictivo a actividades humanas productivas o generadoras de deferencias particulares, aunque no hay tratamiento específico, sino más bien interdisciplinario e individualizado, éste consiste en manejar los síntomas conductuales y la comorbilidad de forma independiente ya sea farmacológica o intervencionista. Paciente masculino de cinco años de edad, con un peso de 26 kg, cuadro de inmunizaciones completas, previamente diagnosticado con trastorno de Asperger (2015); caries dental de diversos grados, manejo estomatológico para su rehabilitación. El objetivo de este reporte es dar a conocer los cuidados para el tratamiento dental en pacientes con este trastorno (AU)

Neurological disorder known as autism spectrum disorders (ASD) whose main manifestations are reflected in the areas of communication, interaction and social imagination. It was first classified in the Diagnostic and Statistical Manual of Mental Disorders (DSM lV), characterized by a greater or lesser degree of deterioration in language and communication skills, as well as repetitive patterns or restrictive of thought and behavior. The most distinctive symptom is obsessive interest in a single object or topic and the exclusion of any other, but always retaining language skills. The prognosis is good in most of the cases, due to the cognitive compensation, the repetitive and restrictive approach to productive or deferential human activities, although there is no specific treatment, but rather interdisciplinary and individualized, this consists of managing behavioral symptoms and comorbidity independently either pharmacologically or interventionally. Male patient with five years old and weight of 26 kg, complete immunization chart, previously diagnosed with Asperger's disorder (2015); with dental caries of various degrees implementing dental management. The objective of this report is to make aware of the care and behavior management for dental treatment in patients with this Disorder (AU)

Graded and pan-neural disease phenotypes of Rett Syndrome linked with dosage of functional MeCP2

Rett syndrome (RTT) is a progressive neurodevelopmental disorder, mainly caused by mutations in MeCP2 and currently with no cure. We report here that neurons from R106W MeCP2 RTT human iPSCs as well as human embryonic stem cells after MeCP2 knockdown exhibit consistent and long-lasting impairment in maturation as indicated by impaired action potentials and passive membrane properties as well as reduced soma size and spine density. Moreover, RTT-inherent defects in neuronal maturation could be pan-neuronal and occurred in neurons with both dorsal and ventral forebrain features. Knockdown of MeCP2 led to more severe neuronal deficits as compared to RTT iPSC-derived neurons, which appeared to retain partial function. Strikingly, consistent deficits in nuclear size, dendritic complexity and circuitry-dependent spontaneous postsynaptic currents could only be observed in MeCP2 knockdown neurons but not RTT iPSC-derived neurons. Both neuron-intrinsic and circuitry-dependent deficits of MeCP2-deficient neurons could be fully or partially rescued by re-expression of wild type or T158M MeCP2, strengthening the dosage dependency of MeCP2 on disease phenotypes and also the partial function of the mutant. Our findings thus reveal stable neuronal maturation deficits and unexpectedly, graded sensitivities of neuron-inherent and neural transmission phenotypes towards the extent of MeCP2 deficiency, which is informative for future therapeutic development.

Factores de riesgo perinatal asociados al trastorno del espectro autista y al síndrome de Rett / Perinatal risk factors associated with autistic spectrum disorder and the Rett syndrome

Resumen El propósito de este proyecto fue identificar los factores de riesgo perinatal asociados al trastorno del espectro autista (TEA) y al síndrome de Rett y compararlos entre sí, estando enmarcado dentro de un estudio de tipo descriptivo. Para esta investigación se utilizó una unidad de análisis conformada por 421 historias clínicas, de las que 377 fueron de TEA y 44 de Rett, a las cuales se les aplicó un instrumento especializado en identificar factores de riesgo perinatales llamado Cuestionario Materno de Riesgo Perinatal (CMRP), con el que se encontró una gran prevalencia de niños nacidos por cesárea y que las ocupaciones de sus padres estaban relacionadas con los cuidados requeridos por el trastorno. Esta identificación de factores servirá para la toma de precauciones a nivel clínico médico y a nivel de prevención de los riesgos asociados al trastorno del espectro autista y el síndrome de Rett.

Abstract The purpose of this project was to identify the perinatal risk factors associated with Autism Spectrum Disorder (ASD) and Rett Syndrome and compare them to each other, being framed within a descriptive study; For this research, an analysis unit consisting of 421 medical records was used, of which 377 were from ASD and 44 from Rett, to which a specialized instrument was applied to identify perinatal risk factors called the Maternal Perinatal Risk Questionnaire (MPRQ ), which found a high prevalence of children born by caesarean section and that their parents' occupations were related to the care required by the disorder. This identification of factors will serve to take precautions at the medical clinical level and at the level of prevention of the risks associated with Autism Spectrum Disorder and Rett Syndrome.

A rare neurodegenerative disorder with a novel mutation in ROGDI and Rett- like phenotype: Kohlschütter- Tönz syndrome

@#Kohlschütter-Tönz syndrome (KTZS) is a rare neurodegenerative disorder that presents with seizures, developmental delay, psychomotor regression, hypoplastic dental enamel morphology characteristic for amelogenesis imperfecta, and dysmorphologies. Genetic analysis has identified loss of function mutations within the coding region of the ROGDI and SLC13A5 genes in KTZS. In this report, we documented the clinical, radiological, electroencephalographic, and genetic results of a 3.5-year-old Turkish girl, born to nonconsanguineous parents, who was the first patient diagnosed with KTZS in Turkey. The patient presented with Rett syndrome-like phenotype, neurodevelopmental delay, refractory seizures, and amelogenesis imperfecta. After obtaining informed consent, chromosomal DNAwas extracted from the peripheral blood of our patient and her parents. To investigate the moleculardiagnosis of the patient, the clinical exome sequencing was performed. The Sanger sequencing analysiswas performed for all of the family members for the validation and segregation of this mutation. PubMed/Medline, Web of Science, and Google Scholar were also searched to find all of the publisheddata on KTZS. The literature comprises 18 published studies about KTZS. The genetic analysis of ourpatient revealed a novel homozygous c.201-1G>T mutation in the ROGDI gene. The same mutationwas also found to be heterozygous in her mother and father. The mutation caused alternative splicingof the ROGDI translation and resulted in a disruption of the ROGDI protein.

Rett syndrome: the Brazilian contribution to the gene discovery / Síndrome de Rett: a contribuição brasileira para a descoberta do gene

ABSTRACT A brief history of the syndrome discovered by Andreas Rett is reported in this paper. Although having been described in 1966, the syndrome was only recognized by the international community after a report by Hagberg et al. in 1983. Soon, its importance was evident as a relatively frequent cause of severe encephalopathy among girls. From the beginning it was difficult to explain the absence of male patients and the almost total predominance of sporadic cases (99%), with very few familial cases. For these reasons, it was particularly difficult to investigate this condition until 1997, when a particular Brazilian family greatly helped in the final discovery of the gene, and in the clarification of its genetic mechanism. Brief references are made to the importance of the MECP2 gene, 18 years later, as well as to its role in synaptogenesis and future prospects.

RESUMO Uma breve história de uma síndrome neurológica descoberta por Andreas Rett é relatada neste artigo. Embora tenha ocorrido em 1966, a síndrome só foi reconhecida pela comunidade internacional após um relato de Hagberget al, em 1983. Logo, sua importância ficou evidente como causa relativamente frequente de encefalopatia grave entre as crianças do sexo feminino. Desde o início, foi difícil explicar a ausência de envolvimento de pacientes do sexo masculino e a quase absoluta preponderância de casos esporádicos (99%), com muitos poucos casos familiares. Por essas razões, foi difícil investigar essa condição até 1997, quando uma família brasileira em particular ajudou muito na descoberta final do gene e no esclarecimento de seu mecanismo genético. São feitas referências sucintas à importância do gene MECP2, dezoito anos depois, bem como ao seu papel na sinaptogênese e nas perspectivas futuras.

Diagnóstico de Rett. Presentación de un caso / Diagnosis of Rett. Presentation of a case

El síndrome de Rett es un trastorno neurológico que afecta casi únicamente a las niñas y mujeres, cuya incidencia en la población general es de un caso por cada 10 000 mujeres, su diagnóstico se basa en la observación y evaluación clínica(AU)

Síndrome de Rett: Análisis molecular del gen MECP2 en pacientes chilenas / Rett syndrome: MECP2 gene molecular analysis in Chilean patients

INTRODUCCIÓN: El síndrome de Rett (RTT) es un trastorno neurológico progresivo caracterizado por producir una regresión del desarrollo psicomotor en niñas previamente sanas. La mayoría de los casos son causados por variantes patogénicas en el gen MECP2, que codifica para la proteína methyl CpG- binding protein 2. OBJETIVO: Describir la frecuencia y el tipo de variantes patogénicas en MECP2 en mujeres chilenas con diagnóstico clínico de RTT. PACIENTES Y MÉTODO: Se invitó a participar en este estudio a mujeres chilenas con sospecha clínica de RTT. Se reunió información clínica mediante un cuestionario. Se analizaron variantes patogénicas en MECP2 mediante el método de secuenciación de Sanger y se utilizó Multiple Ligation-dependant Probe Amplification (MLPA) para la detección de duplicaciones y deleciones. RESULTADO: El estudio incluyó 14 pacientes con sospecha de RTT, de las cuales 8 (57%) pacientes tuvieron variantes patogénicas. Las restantes permanecen sin diagnóstico molecular. CONCLUSIÓN: Variantes patogénicas en MECP2 están presentes en pacientes chilenas con RTT. Es probable que haya otros genes o diagnósticos involucrados en las pacientes sin hallazgos en MECP2. A partir de este trabajo, el diagnóstico molecular está disponible en Chile.

INTRODUCTION: Rett syndrome (RTT) is a progressive neurological disorder characterized by regres sion of psychomotor development in previously healthy girls. Most cases are due to pathogenic va riants in the MECP2 gene which encodes for the methyl CpG-binding protein 2. OBJECTIVE: To des cribe the frequency and type of pathogenic variants in the MECP2 gene in Chilean female patients with clinical diagnosis of RTT. PATIENTS AND METHOD: Chilean women with clinical suspicion of RTT were invited to participate in the study. Clinical data were collected through a questionnaire. MECP2 pathogenic variants were analyzed by Sanger sequencing method and Multiplex Ligation-dependent Probe Amplification (MLPA) was used to detect duplications or deletions. RESULTS: The study in cluded 14 patients with suspected RTT, of which eight (57%) patients had pathogenic variants. The other patients remain without molecular diagnosis. CONCLUSIONS: Pathogenic variants in MECP2 are present in Chilean patients with RTT. It is likely that there are other genes or diagnoses involved in patients without MECP2 findings. As of this study, molecular diagnosis is available in Chile.

Positive effects of low dose IMPX977 on Rett syndrome related MeCP2 targeted-genes / 中草药·英文版

Objective: To investigate the effect of IMPX977 on MeCP2 targeted-genes and the feasibility of IMPX977 acting as a therapeutic candidate drug for Rett syndrome by genomewide transcription profiling. Methods: Rats’ cortex of control group, IMPX977-treated low-dose group (10 mg/kg), and IMPX977-treated high-dose group (30 mg/kg) were collected and RNA was extracted from the tissues. Then, RNA was subjected to RNA-sequencing. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) were used in functional enrichment analysis of differentially expressed genes. Results: Six MeCP2 targeted-genes were identified in the low/control categories, but not in the high/control categories. Conclusion: Low-dose treatment of IMPX977 (10 mg/kg) showed a positive effect on MeCP2 targeted-genes and it may serve as a drug candidate for Rett syndrome therapy with proper dosage.

Transtornos autísticos e estratégias promotoras de cuidados: revisão integrativa / Trastornos autísticos y estratégias promotoras de cuidados: revisión integradora / Autistic disorders and care promotion strategies: integrative review

Objetivo analisar a produção científica brasileira recente sobre Transtornos do Espectro Autista, identificando as estratégias de cuidados investigadas. Método revisão integrativa de literatura na base de dados LILACS e na biblioteca virtual SciELO. Foram selecionados artigos publicados entre 2011 e 2017, utilizando os descritores Transtorno Autístico, Síndrome de Asperger e Síndrome de Rett. Resultados vinte e quatro artigos foram caracterizados e analisados descritivamente, com exposição dos seus níveis de evidência. Doze estudos (50%) representavam pesquisas descritivas, nível de evidência VI. Onze estudos (45,8%) equivaliam a delineamento não experimental, nível de evidência IV. A estratégia mais estudada foi de diagnóstico e avaliação para a prática clínica, com aplicação de instrumentos já validados, seguida de avaliação de resultados terapêuticos. Conclusão a produção científica brasileira atual sobre Transtorno do Espectro Autista mostrou-se direcionada para o enfoque diagnóstico nas áreas de fonoaudiologia e psicologia.

Objetivo analizar la producción científica brasileña reciente sobre Trastornos del Espectro Autista, identificando las estrategias de cuidados investigadas. Método revisión integradora de literatura en la base de datos LILACS y en la biblioteca virtual SciELO. Fueron seleccionados artículos publicados entre 2011 y 2017, utilizando los descriptores Trastorno Autístico, Síndrome de Asperger y Síndrome de Rett. Resultados veinte y cuatro artículos fueron caracterizados y analizados descriptivamente, con exposición de sus niveles de evidencia. Doce estudios (50%) representaban investigaciones descriptivas, nivel de evidencia VI. Once estudios (45,8%) correspondían a diseño no experimental, nivel de evidencia IV. La estrategia más estudiada fue de diagnóstico y evaluación para la práctica clínica, con aplicación de instrumentos ya validados, seguida de evaluación de resultados terapéuticos. Conclusión la producción científica brasileña actual sobre Trastorno del Espectro Autista se mostró orientada al enfoque diagnóstico en las áreas de fonoaudiología y psicología.

Objective to analyze the recent Brazilian scientific production about Autism Spectrum Disorders, identifying the investigated care strategies. Method integrative literature review in the database LILACS and in the virtual library SciELO. Articles published between 2011 and 2017 were selected, using the descriptors Autistic Disorder, Asperger Syndrome and Rett Syndrome. Results twenty four articles were characterized and analyzed descriptively, and their levels of evidence were presented. Twelve studies (50%) represented descriptive research, level of evidence VI. Eleven studies (45.8%) had non-experimental designs, level of evidence IV. The most studied strategy was the diagnosis and evaluation for clinical practice, by applying validated tools, followed by the assessment of therapeutic outcomes. Conclusion current Brazilian scientific production about Autism Spectrum Disorder was focused on diagnosis in speech therapy and psychology.

Envejecimiento en personas con trastorno del espectro autista / Aging in people with autism spectrum disorder

El trastorno del espectro autista se caracteriza por una alteración cualitativa en la interacción social y la comunicación, asociada a intereses restringidos y conductas estereotipadas. Esta condición acompañará a las personas a lo largo de toda la vida, con variaciones en su evolución. Nuestros objetivos fueron conocer las características evolutivas de las personas con trastorno del espectro autista, analizando aspectos cognitivos, conductuales, salud, mortalidad y sus necesidades en la etapa de envejecimiento, que permitan orientar la planificación de recursos específicos de apoyo. Se analizaron estudios relacionados con la evolución en la vida adulta en personas con este trastorno, con o sin entidades identificadas, y las condiciones sociosanitarias que deben ser consideradas en los procesos de envejecimiento. El conocimiento sobre el envejecimiento en personas con autismo es aún escaso y resulta difícil definir un patrón específico pues este dependerá, entre otros factores, de la etiología, el grado, la presencia de discapacidad intelectual y/o epilepsia, y el ámbito en el que viven, los cuales pueden incluso condicionar la expectativa de vida. El envejecimiento se ha asociado a trastornos del humor, depresión, deterioro en funciones ejecutivas y memoria episódica, aunque resulta difícil diferenciarlo del envejecimiento natural en personas con desarrollo típico. La identificación de una entidad específica permitirá conocer la posible evolución y prevenir complicaciones en síndromes que pueden estar asociados con autismo: X frágil, Down, Angelman, Rett y Williams, por ello jerarquizamos la consulta genética y neurológica.

Autism spectrum disorder is characterized by a qualitative alteration in social interaction and communication associated with restricted interests and stereotyped behaviors. This condition will accompany people throughout their lives, with variations in their evolution. Our objectives were to know the evolutionary characteristics of people with autistic spectrum disorder, analyzing cognitive, behavioral, health, mortality and their needs in the aging stage, which will guide the planning of specific support resources. We analyze studies related to the evolution in adult life in people with this disorder, with or without identified entities, and socio-health conditions that should be considered in the aging process. The knowledge about aging in people with autism is still scarce and it is difficult to define a specific pattern because this will depend, among other factors, on the etiology, the degree, the presence of intellectual disability and/or epilepsy, and the scope in where live, which can even condition the life expectancy. Aging has been associated with mood disorders, depression, deterioration in executive functions and episodic memory, although it is difficult to differentiate it from natural aging in people with typical development. The identification of a specific entity will allow to know the possible evolution and prevent complications in syndromes that may be associated with autism: fragile X, Down, Angelman, Rett and Williams, for that reason we rank the genetic and neurological consultation.

Anesthetic management of a pediatric patient with Rett syndrome: A case report

Rett syndrome is a neurodevelopmental disease that almost always affects female patients. It is caused by mutations in MeCP2 in the majority of cases. Patients diagnosed with Rett syndrome may experience serious adverse events even with smaller amounts of medication for sedation and anesthesia. The major anesthetic concerns associated with Rett syndrome are lack of cooperation, abnormal continuous limb movements, abnormal respiratory control, difficult positioning secondary to scoliosis, and altered sensitivity to painful stimuli. Because of the risks caused by these problems, anesthesiologists should be aware of the specific anesthetic concerns of patients with Rett syndrome in order to safely administer anesthesia. Here, we describe the management of a pediatric patient diagnosed with Rett syndrome.

Novel FOXG1 mutation in a patient with congenital Rett variant: a case report / 天津医药

@#Objective To summarize the clinical features of children with congenital Rett variant caused by mutation of FOXG1 and provide the reference for the diagnosis and treatment of the disease. Methods The clinical data of a patient diagnosed as congenital Rett syndrome variant type were summarized. The DNA samples of peripheral blood from the patient and her parents were extracted. The targeted high-throughput sequencing technology was used to detect the sequence of targeted genes, which were associated with the symptoms of the child. Genes were then verified by sanger sequencing. Chromosomal microarray analysis was performed to detect chromosome microdeletions and microduplications. Results The child carried the c.506dupG, p.G169Gfs＊ 286 heterozygous mutations on FOXG1 gene, which located in 14q12, and her parents were wild-type. After querying the HGMD, Clinvar and dbSNP databases, we found that it was not reported. This case was clearly diagnosed as congenital Rett syndrome variant type. We confirmed that the mutation locus was a new mutation. Conclusion For cases with congenital Rett variant manifestations, FOXG1 gene mutation examination is recommended, and preventive treatment of partially predictable dysfunction should be carried out.

Updates on pathogenesis-related genes and diagnosis and treatment of Rett syndrome / 国际儿科学杂志

Rett syndrome ( RTT) is a devastating neurological disorder that is caused largely by muta-tions in the X-linked gene MECP2,other two genes associated with RTT are CDKL5 and FOXG1. RTT is one of the most common causes of mental retardation in girls,male cases are rare. Classical features of typical RTT in-clude losing acquired spoken language and hand skills,hand stereotypies,epilepsy and respiratory disorders. The diagnosis of RTT mainly depends on the clinical characteristics. Atpresent, it still lacks atargeted treatment. In this review,we summarize both the gene research,diagnosis and treatmentprogresses of RTT so as to improve the understanding of RTT.

Use of sugammadex in Rett syndrome: A case report

Rett syndrome (RS) is a neurodevelopmental disorder characterized by loss of cognitive, motor, and social skills, epilepsy, autistic behavior, abnormal airway patterns, gastroesophageal reflux, nutritional problems, and severe scoliosis. Although girls with RS show normal or near-normal growth until 6–8 months, they lose their skills after that. The anesthetic management of these patients requires care because of all these clinical features. Especially in the postoperative period, prolonged apnea is common and extubation is delayed. In this case report, the effect of using sugammadex was presented in a 16-year-old girl with RS. The patient's all bimaxillary teeth and 4 wisdom teeth were extracted under general anesthesia in one session with minimal surgical trauma and moderate bleeding. Sugammadex can be a rapid and reliable agent for the reversal of the neuromuscular block in neurodegenerative patients.

Síndrome de Rett: revisión de la literatura con primeros casos reportados en Colombia con caracterización clínica y molecular / Rett syndrome: review of the literature and first cases reported in Colombia with clinical characterization and molecular diagnosis

RESUMEN INTRODUCCIÓN: El síndrome de Rett es una condición neurológica severa y la segunda causa genética de retraso mental profundo en mujeres. Se genera por mutaciones en el gen MECP2 y es caracterizada por una pérdida de las ganancias psicomotoras, con una prevalencia general estimada de 1:10.000 niñas, según la extrapolación de algunos estudios europeos. OBJETIVOS: Realizar una revisión de la literatura sobre el síndrome de Rett y presentar una serie de casos diagnosticados en Colombia por clínica y prueba molecular. METODOLOGÍA: Se efectuó una búsqueda bibliográfica y de reportes de casos en 21 bases de datos internacionales, más de 14 revistas del área de la salud y dos motores de búsqueda generales entre 2014 y 2016. Los casos presentados fueron seleccionados de la consulta de genética médica realizada por los autores. HALLAZGOS: No se encontró ningún caso colombiano de síndrome de Rett, ni confirmado con prueba molecular en Latinoamérica. Se reporta así la primera serie de casos nacional y la mayor latinoamericana, conformada por siete pacientes con tipo clásico y tres atípicos, todas con diagnóstico molecular. CONCLUSIONES: Pese a tener una evolución clínica caracterizada, su baja prevalencia y amplio espectro clínico convierten al síndrome de Rett en un reto diagnóstico y terapéutico. La mutación c.749_750insT se reporta por primera vez, la c.473C>G por segunda en la literatura y la c.763C>T se presenta en dos pacientes con fenotipos totalmente distintos, lo que confirma la no correlación genotipo-fenotipo de la enfermedad.

SUMMARY INTRODUCTION: Rett Syndrome is a severe neurological condition and the second genetic cause of profound mental retardation in women. It is generated by mutations in the MECP2 gene and it is characterized by a loss of psychomotor gains, with an estimated overall prevalence of 1:10,000 girls, according to the extrapolation of some European studies. Objectives. To make a review of Rett Syndrome and to present a series of cases diagnosed in Colombia by clinical criteria and molecular tests. METHODOLOGY: We made a bibliographic research in 21 international databases, more than 14 health journals and two general search engines between 2014 and 2016. The cases presented were selected from the Medical Genetics consultation carried out by the authors. FINDINGS: No Colombian case of Rett Syndrome was found nor confirmed with molecular testing in Latin America. We report the first cases in Colombia and the largest in Latin America, consisting of seven patients with classic type and three with atypical type, all with molecular diagnosis. CONCLUSIONS: In spite of having a characterized clinical evolution, its low prevalence and broad clinical spectrum, make Rett Syndrome a diagnostic and therapeutic challenge. We report for the first time the mutation c.749_750insT, the c.473C> G for second time in the literature and the c.763C> T is presented in two patients with totally different phenotypes, confirming the non-correlation genotype-phenotype of the disease.

Valoración bioquímica de la saliva, orina y material fecal de pacientes pediátricos con trastornos del espectro autista (TEA) / Biochemical assessment of saliva, urine and fecal samples in pediatric patients with autism spectrum disorders

En un grupo de 46 niños y adolescentes (5-14 años de edad) con trastornos del espectro autista, consumo elevado de harinas y azucares en su dieta y antecedentes de consumo de antibióticos frecuentes, se analizan muestras de saliva, orina y materia fecal (n=15). Comparados con muestras de un grupo normal (n=10), se detectan variaciones significativas en el pH salival, tiempo de recuperación del pH, viscosidad, flujo, y valores elevados de IgA e IgG en saliva. En orina predomina la proteinuria y la acidez, en la materia fecal no se hallaron parásitos ni C albicans. Estos cambios pueden responder a fenómenos alérgicos y alteraciones de la permeabilidad intestinal aspectos que deben ser investigados luego, pero los resultados muestran variantes significativas que permitirán elegir los sujetos preferentes para futuras investigaciones y/o generar la sospecha para la derivación temprana de pacientes sin diagnóstico y con síntomas mínimos (AU)

Samples of saliva, urine and fecal (n=15) was analyzed in a group of 46 children and teenagers (5-14 years old) with autism spectrum disorders, high consumption of flour and sugar with diet, and a history of frequent antibiotic consumption. Compared to a group of normal children (n=10), significant variations in saliva composition as pH, time to pH recovery, viscosity, flux and IgA and IgG concentration were observed, proteinuria and acidity findings predominate in the urinalysis, and the absence of parasites and C Albicans were notices at the fecal samples. These changes can respond to immune-allergic and intestinal permeability conditions, aspects that should be further investigated. Patients with these findings can be preferentially select for future studies and/ or generate suspects in undiagnosed individuals with minimal symptoms that can be early derive to proper treatment (AU)

Comprehensive Evaluation on Effect of IMPX977 on Expression of Methyl-CpG-binding Protein 2 in Rats / 中草药·英文版

Objective To investigate the effect of IMPX977 on methyl-CpG-binding protein 2 (MeCP2) expression in rats. Methods Forty-eight SD rats were randomly divided into four groups: normal control group, olive oil (negative control, 5 mL/kg oil) group, and 10 mg/kg and 30 mg/kg IMPX977 administration groups. All rats were given corresponding dose of drugs each other day and administered orally for two weeks. Tissues including cortex and cerebellum were collected from rats to assay the expression of MeCP2 by quantitative RT-PCR and Western blotting. Results The IMPX977 supplement showed no significant effect on the body weight of rats. In normal rats, MeCP2 was highly expressed in cerebellum, cortex and hippocampus, and less expressed in heart, spleen and lung. In addition to male rats, compared with the control group, the expression of MeCP2 mRNA was significantly increased in cerebellum after 30 mg/kg IMPX977 treatment and contrarily, absolutely decreased in cortex of all treatment groups. Furthermore, in female rats MeCP2 mRNA was reduced in cortex of both olive oil and 30 mg/kg IMPX977 treatment groups compared with control group. Meanwhile, MeCP2 protein level was significantly elevated in cerebellum of treated male rats compared to the control group. In contrast to the control group, the expression of MeCP2 protein in both cerebellum and cortex of female rats in other three groups was increased. Conclusion IMPX977 treatment (10 mg/kg) may elevate the expression of MeCP2, which establishes experimental foundation for the further research on rat models of Rett syndrome.