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Rett syndrome (RTT) is an early-onset neurodevelopmental disorder that is caused by mutations in the MECP2 gene; however, defects in other genes (CDKL5 and FOXG1) can lead to presentations that resemble classic RTT, although they are not completely identical. Here, we attempted to identify other monogenic disorders that share features of RTT. A total of 437 patients with a clinical diagnosis of RTT-like were studied; in 242 patients, a custom panel with 17 genes related to an RTT-like phenotype was run via a HaloPlex-Target-Enrichment-System. In the remaining 195 patients, a commercial TruSight-One-Sequencing-Panel was analysed. A total of 40 patients with clinical features of RTT had variants which affect gene function in six genes associated with other monogenic disorders. Twelve patients had variants in STXBP1, nine in TCF4, six in SCN2A, five in KCNQ2, four in MEF2C and four in SYNGAP1. Genetic studies using next generation sequencing (NGS) allowed us to study a larger number of genes associated with RTT-like simultaneously, providing a genetic diagnosis for a wider group of patients. These new findings provide the clinician with more information and clues that could help in the prevention of future symptoms or in pharmacologic therapy.

Orality had an important role in many aspects of early modern experience, and political institutions and counsel are no exceptions. Conversational manners, voice, style of speech, wit, and erudition were all key elements in counselling and for the self-representation of counsellors. Moreover, oral communication was crucial at court and contemporaries aimed to influence and control the distribution of such information to different ends. Scholars have extensively used documentation produced by councils as the basis for minute recreations of political events and administrative changes, but the oral practices of counsel have been largely ignored. This article examines the orality of Habsburg councils and focuses on actual modes of performing counsel. In particular, it reconstructs the complex process of production of written documentation as part of a broader communicative flow and aims to show that notions of style and voice affected the ways in which councils were perceived as instruments for government. Finally, it analyses how conversations were regulated, obstructed, or manipulated and the value attributed to voting procedures, consensus, and dissent within an aristocratic and hierarchical notion of council.

Resumen: Introducción: La neurofibromatosis tipo 1 (NF1) es un trastorno genético con manifestaciones clínicas muy variables que pueden expresarse en el sistema nervioso central y periférico, así como en piel, hueso, sistema endocrinológico y vascular. Los aspectos neuropsicológicos de la NF1 en la infancia continúan sin ser suficientemente conocidos, existiendo controversia acerca de los posibles déficits que definen el perfil cognitivo de estos niños. Objetivo: Estudiar el rendimiento neuropsicológico de un grupo de pacientes con NF1 en comparación con un grupo de control de niños sanos. Sujetos y método: Se estudia el rendimiento neuropsicológico de un grupo de 23 niños y niñas con diagnóstico de NF1, con una edad media de 8,7 años ± 1,39 comparado con otro grupo formado por 21 niños sanos con una edad media de 8,9 años ± 1,41 con características sociodemográficas similares. A todos los sujetos se les aplicó la Escala de Inteligencia de Wechsler infantil (WISC-IV). Resultados: Se observa en el grupo con NF1 un rendimiento menor que el grupo control en los índices globales del WISC-IV: comprensión verbal, razonamiento perceptivo, memoria de trabajo, velocidad de procesamiento y cociente intelectual global. Únicamente en los subtest de claves y semejanzas no se han apreciado diferencias estadísticamente significativas entre ambos grupos. Conclusión: Los resultados reflejan la existencia de alteraciones neurocognitivas sutiles y generalizadas en la muestra de niños con NF1, que afectan a la mayoría de los dominios cognitivos evaluados. Se subraya la necesidad de que reciban una atención neuropsicológica específica precoz para prevenir el mayor riesgo de presentar dificultades de aprendizaje y fracaso escolar. Abstract: Introduction: Neurofibromatosis type 1 (NF1) is a genetic disorder with various clinical manifestations that affect the peripheral and central nervous system, as well as the skin, bones and endocrine and vascular system. There is still insufficient knowledge of neuropsychological effects of NF1 on children, and there is some controversy about the cognitive deficits that defines the cognitive profile of patients affected by this disorder. Aims: In this study an analysis is made of the neuropsychological performance of a group of patients affected by NF1, compared with a control group of healthy children. Subjects and method: A comparison was made between the neuropsychological performance of a group of 23 boys and girls with a mean age of 8.7 years (+/-1.39) and diagnosed with NF1, and a control group consisting of 21 healthy children, with mean age of 8.9 years (+/- 1.41) and with similar socio-demographic characteristics. The Wechsler Intelligence Scale for Children (WISC) was applied to evaluate the subjects of both groups. Results: The group of patients affected with NF1 showed a lower performance in every primary index of WISC IV: Verbal Comprehension Index, Fluid Reasoning Index, Working Memory Index, Processing Speed Index, and full Scale IQ. Only in two subscales were no statistically significant differences observed: similarities and coding. Conclusion: The results show subtle and generalised neuropsychological alterations in the sample of children affected with NF1, which affect most of cognitive domains that have been evaluated. Proper specific and early neuropsychological treatment should be provided in order to prevent the high risk for these children of presenting learning difficulties and school failure.

Introduction: Neurofibromatosis type 1 (NF1) is a genetic disorder with various clinical manifestations that affect the peripheral and central nervous system, as well as the skin, bones and endocrine and vascular system. There is still insufficient knowledge of neuropsychological effects of NF1 on children, and there is some controversy about the cognitive deficits that defines the cognitive profile of patients affected by this disorder. Aims: In this study an analysis is made of the neuropsychological performance of a group of patients affected by NF1, compared with a control group of healthy children. Subjects and method: A comparison was made between the neuropsychological performance of a group of 23 boys and girls with a mean age of 8.7 years (+/−1.39) and diagnosed with NF1, and a control group consisting of 21 healthy children, with mean age of 8.9 years (+/−1.41) and with similar socio-demographic characteristics. The Wechsler Intelligence Scale for Children (WISC) was applied to evaluate the subjects of both groups. Results: The group of patients affected with NF1 showed a lower performance in every primary index of WISC IV: Verbal Comprehension Index, Fluid Reasoning Index, Working Memory Index, Processing Speed Index, and full scale IQ. Only in two subscales were no statistically significant differences observed: similarities and coding. Conclusion: The results show subtle and generalised neuropsychological alterations in the sample of children affected with NF1, which affect most of cognitive domains that have been evaluated. Proper specific and early neuropsychological treatment should be provided in order to prevent the high risk for these children of presenting learning difficulties and school failure. Resumen: Introducción: La neurofibromatosis tipo 1 (NF1) es un trastorno genético con manifestaciones clínicas muy variables que pueden expresarse en el sistema nervioso central y periférico, así como en piel, hueso, sistema endocrinológico y vascular. Los aspectos neuropsicológicos de la NF1 en la infancia continúan sin ser suficientemente conocidos, existiendo controversia acerca de los posibles déficits que definen el perfil cognitivo de estos niños. Objetivo: Estudiar el rendimiento neuropsicológico de un grupo de pacientes con NF1 en comparación con un grupo de control de niños sanos. Sujetos y método: Se estudia el rendimiento neuropsicológico de un grupo de 23 niños y niñas con diagnóstico de NF1, con una edad media de 8,7 años ± 1,39 comparado con otro grupo formado por 21 niños sanos con una edad media de 8,9 años ± 1,41 con características sociodemográficas similares. A todos los sujetos se les aplicó la Escala de Inteligencia de Wechsler infantil (WISC-IV). Resultados: Se observa en el grupo con NF1 un rendimiento menor que el grupo control en los índices globales del WISC-IV: comprensión verbal, razonamiento perceptivo, memoria de trabajo, velocidad de procesamiento y cociente intelectual global. Únicamente en los subtest de claves y semejanzas no se han apreciado diferencias estadísticamente significativas entre ambos grupos. Conclusión: Los resultados reflejan la existencia de alteraciones neurocognitivas sutiles y generalizadas en la muestra de niños con NF1, que afectan a la mayoría de los dominios cognitivos evaluados. Se subraya la necesidad de que reciban una atención neuropsicológica específica precoz para prevenir el mayor riesgo de presentar dificultades de aprendizaje y fracaso escolar.