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Fragile X syndrome (FXS) is the leading cause of inherited intellectual disability. The objective of this research is to analyze the relationship between linguistic functions and performance of the following neuropsychological functions: executive, quantitative reasoning, social perception, behavior, social skills, and adaptive behavior. A neuropsychological and behavioral evaluations were carried out with a group of 26 girls with FXS, and 14 girls without FXS as a control group, using standardized tests. The two groups were homogeneous in age and IQ. Significant differences were found between groups in the relationship between some language processes: inhibition, auditory working memory, cognitive flexibility, level of social adaptation, self-direction, conceptual adaptation, academic skills, leadership ability, theory of mind, and arithmetic. In the group of girls with FXS, it was found that different aspects of language influence some of the executive functions evaluated, in addition to some specific aspects of social perception, adaptive behavior, and quantitative reasoning, in different ways. Future research should incorporate the study of the influence of other cognitive variables such as visual perception and executive function on behavioral, social, and adaptive aspects to know the real influence of all the cognitive variables on the behavior of girls with FXS.

PURPOSE: Inborn errors of neurotransmitters are rare monogenic diseases. In general, conventional neuroimaging is not useful for diagnosis. Nevertheless, advanced neuroimaging techniques could provide novel diagnosis and prognosis biomarkers. We aim to describe cerebral volumetric findings in a group of Spanish patients with neurotransmitter disorders. METHODS: Fifteen 3D T1-weighted brain images from the International Working Group on Neurotransmitter related Disorders Spanish cohort were assessed (eight with monoamine and seven with amino acid disorders). Volumes of cortical and subcortical brain structures were obtained for each patient and then compared with those of two healthy individuals matched by sex and age. RESULTS: Regardless of the underlying disease, patients showed a smaller total cerebral tissue volume, which was apparently associated with clinical severity. A characteristic volumetric deficit pattern, including the right Heschl gyrus and the bilateral occipital gyrus, was identified. In severe cases, a distinctive pattern comprised the middle and posterior portions of the right cingulate, the left superior motor area and the cerebellum. In succinate semialdehyde dehydrogenase deficiency, volumetric affection seems to worsen over life. CONCLUSION: Despite the heterogeneity and limited size of our cohort, we found novel and relevant data. Total volume deficit appears to be a marker of severity, regardless of the specific neurotransmitter disease and irrespective of the information obtained from conventional neuroimaging. Volumetric assessment of individual brain structures could provide a deeper knowledge about pathophysiology, disease severity and specific clinical traits.

PURPOSE: Inborn errors of neurotransmitters are rare monogenic diseases. In general, conventional neuroimaging is not useful for diagnosis. Nevertheless, advanced neuroimaging techniques could provide novel diagnosis and prognosis biomarkers. We aim to describe cerebral volumetric findings in a group of Spanish patients with neurotransmitter disorders. METHODS: Fifteen 3D T1-weighted brain images from the International Working Group on Neurotransmitter related Disorders Spanish cohort were assessed (eight with monoamine and seven with amino acid disorders). Volumes of cortical and subcortical brain structures were obtained for each patient and then compared with those of two healthy individuals matched by sex and age. RESULTS: Regardless of the underlying disease, patients showed a smaller total cerebral tissue volume, which was apparently associated with clinical severity. A characteristic volumetric deficit pattern, including the right Heschl gyrus and the bilateral occipital gyrus, was identified. In severe cases, a distinctive pattern comprised the middle and posterior portions of the right cingulate, the left superior motor area and the cerebellum. In succinate semialdehyde dehydrogenase deficiency, volumetric affection seems to worsen over life. CONCLUSION: Despite the heterogeneity and limited size of our cohort, we found novel and relevant data. Total volume deficit appears to be a marker of severity, regardless of the specific neurotransmitter disease and irrespective of the information obtained from conventional neuroimaging. Volumetric assessment of individual brain structures could provide a deeper knowledge about pathophysiology, disease severity and specific clinical traits.

Comportamiento adaptativo; Escuela; Niñas Comportament adaptatiu; Escola; Nenes Adaptive behavior; School; Young females The aim of this research is to analyze the relationship between executive functions and adaptive behavior in girls with Fragile X syndrome (FXS) in the school setting. This study is part of a larger investigation conducted at the Hospital Parc Tauli in Sabadell. The sample consists of a total of 40 girls (26 with FXS and 14 control) aged 7–16 years, who were administered different neuropsychological tests (WISC-V, NEPSY-II, WCST, TOL) and questionnaires answered by teachers (ABAS-II, BRIEF 2, ADHD Rating Scale). The results show that there is a greater interaction between some areas of executive function (cognitive flexibility, auditory attention, and visual abstraction capacity) and certain areas of adaptive behavior (conceptual, practical, social, and total domains) in the FXS group than in the control group. These results suggest that an alteration in the executive functions was affecting the daily functioning of the girls with FXS to a greater extent. The study was awarded two scholarships by the “Parc Tauli Foundation”: (1) Financial assistance to cover part of the travel expenses (transportation and accommodation). Grant number: 2018.0035; (2) “Intensifica’t al Tauli” Scholarship: grant program for the institutions’ healthcare professionals who led research projects. This financial assistance partially frees them from their professional activity for a period of 12 months so that they can make a greater commitment to research. Grant number: 2020.0081.

Cistus heterophyllus subsp. carthaginensis es un endemismo iberolevantino catalogado como en peligro crítico por la UICN (Unión Internacional para la Conservación de la Naturaleza). Desde su descubrimiento y descripción, se han llevado a cabo numerosas acciones para su conservación. En este trabajo se ha llevado a cabo un análisis del área potencial del taxon en la provincia de Alicante mediante el software libre de información geográfica QGIS, teniendo en cuenta como factores principales la temperatura y las precipitaciones idóneas para la especie, además de otros factores secundarios que pueden ayudar a asegurar y facilitar una introducción adecuada de la planta al medio. Todo ello con el objetivo de lograr definir zonas potenciales de reintroducción para el taxon, siempre según criterios ecológicos adecuados. Los resultados obtenidos sugieren que existe una amplia área potencial donde sería posible realizar labores de conservación, siendo las zonas más destacables las de la Font del Molí, el sur de la Sierra de Bernia y el Valle del Sol. No obstante, estos resultados no se corresponden con el área propuesta por el Plan de Recuperación del taxon en la Comunidad Valenciana, por lo que tienen un elevado valor de cara a ser considerados en futuros reajustes de éste.

Girls with Fragile-X-Syndrome (FXS) present high levels of social anxiety, social avoidance, extreme shyness, tendency to social isolation, poor eye contact, learning difficulties, and depression. The aims of the present study, which is based on a group of young females with FXS are: 1) to analyze the possible associations between emotion recognition, theory of mind, and social anxiety, and adaptive behavior, and emotional state; 2) to study the relationship between intelligence quotient (IQ) and adaptive behavior; and 3) to assess whether social anxiety is more prevalent in girls with FXS. The study has 40 female participants aged between 7 and 16 years (26 positive full mutation FXS and 14 as a control group). A neuropsychological assessment was conducted using the following tests: WISC-V, NEPSY-II, SENA, ADHD Rating Scale, BAS, and ABAS-II. In comparison with the control group, the group with FXS presented a greater association between IQ and self-direction ability, and between emotion recognition and leadership. The FXS group presented higher levels of social anxiety and shyness. In the group of girls with FXS, IQ may have prognostic value for both self-direction ability and social adaptation level.

Introduction The aim of this study is to describe the relationship between executive function (EF) and performance in different areas of the neurocognitive profile in young girls with Fragile-X-Syndrome (FXS). Method A neuropsychological assessment was carried out to 40 female participants aged 7–16 years (26 FXS, 14 control group). Results Regarding intellectual ability, in the group of girls with FXS 3.84 % of the participants obtained IQ scores in the range of moderate ID (IQ 35–40 to 49), 46.15 % in the range of mild ID (IQ 50–70), 38.46 % in the borderline range (IQ 70–85), and 11.53 % within the average range (IQ > 85). EF was found to have a greater influence on adaptive behavior, arithmetic ability, theory of mind, leadership, social integration, social competence, and anxiety/shyness in the group with FXS. Conclusions In girls with FXS, EF showed a greater influence on adaptive behavior, arithmetic ability, and social domain.

The aim of this study is to investigate the risk associated with girls with fragile X syndrome (FXS) suffering bullying in the role of a victim and its effects on their adaptive behavior, socialization style, and emotional state. A neuropsychological assessment was carried out on a sample of 40 participants (26 FXS positive and 14 control group) using the following instruments: WISC-V, SENA, BAS-2, ABAS-II. The results show that the group of girls with FXS presented higher ratios of lack of social support and isolation from classmates. This finding suggests that problems with social interaction and communication in the group of girls with FXS could lead to difficulties in interpreting social signals and identifying situations of bullying correctly, placing them in a very vulnerable situation.

Rett spectrum disorder is a progressive neurological disease and the most common genetic cause of intellectual disability in females. MECP2 is the major causative gene. In addition, CDKL5 and FOXG1 mutations have been reported in Rett patients, especially with the atypical presentation. Each gene and different mutations within each gene contribute to variability in clinical presentation, and several groups worldwide performed genotype-phenotype correlation studies using cohorts of patients with classic and atypical forms of Rett spectrum disorder. The Rett Networked Database is a unified registry of clinical and molecular data of Rett patients, and it is currently one of the largest Rett registries worldwide with several hundred records provided by Rett expert clinicians from 13 countries. Collected data revealed that the majority of MECP2-mutated patients present with the classic form, the majority of CDKL5-mutated patients with the early-onset seizure variant, and the majority of FOXG1-mutated patients with the congenital form. A computation of severity scores further revealed significant differences between groups of patients and correlation with mutation types. The highly detailed phenotypic information contained in the Rett Networked Database allows the grouping of patients presenting specific clinical and genetic characteristics for studies by the Rett community and beyond. These data will also serve for the development of clinical trials involving homogeneous groups of patients.

En el siguiente trabajo se analizaran las lesiones deportivas, en concreto las lesiones deligamento cruzado anterior (LCA), estudiando la distribución de estas lesiones segúnsexo, tipo de deporte, edad, tiempo que estuvo sin poder realizar actividad física, si fuenecesaria cirugía, si preciso de rehabilitación, como se produjo y porque se produjo.Tras la realización concluyo que las mujeres son más propensas a dicha lesión, ademásson factores importantes la interacción del terreno de juego y el equipamiento, porúltimo es conveniente implantar programas de prevención.

RTT girls suffer periods of abnormal behavior from early infancy, including irritability and sleep disorders or anxiety in the first years of life, and a more depressed mood after adolescence, all of which influences their quality of life. An association between emotional and behavioral disorders and various neurochemical changes in the synapses of cortical and subcortical brain regions has been established; also, cortisol levels in the blood vary during stress. The main purpose of this study was to improve mood and behavior disorders in RTT patients with venlafaxine (SNRI), and compare the results with citalopram (SSRIs) during 6 - 8 weeks, to determine which drug offered greater efficacy and fewer side effects, as well as to compare them to risperidone, and to correlate cortisol levels in saliva with stress and drug response. Eleven patients, aged 5 to 26 years old, agreed to participate in this study; neuropsychological tests (Mullen and Vineland scales), quality of life and quality of sleep scales, blood tests, EKG and EEG were performed before and after treatment. Only 2 patients completed the three months trial. Improvement in mood and behavior was not statistically significant for patients; differences in neurodevelopment and quality of life or sleep scales were not significant either; no serious adverse effects were observed. Cortisol levels in saliva decreased in 50% of the patients after the first month of treatment, although this was not statistically significant.

Reflex seizures are a rare phenomenon among epileptic patients, in which an epileptic discharge is triggered by various kinds of stimuli (visual, auditory, tactile or gustatory). Epilepsy is common in Rett syndrome patients (up to 70%), but to the authors' knowledge, no pressure or eating-triggered seizures have yet been reported in Rett children. We describe three epileptic Rett patients with reflex seizures, triggered by food intake or proprioception. One patient with congenital Rett Sd. developed infantile epileptic spasms at around seven months and two patients with classic Rett Sd. presented with generalised tonic-clonic seizures at around five years. Reflex seizures appeared when the patients were teenagers. The congenital-Rett patient presented eating-triggered seizures at the beginning of almost every meal, demonstrated by EEG recording. Both classic Rett patients showed self-provoked pressure -triggered attacks, influenced by stress or excitement. Non-triggered seizures were controlled with carbamazepine or valproate, but reflex seizures did not respond to antiepileptic drugs. Risperidone partially improved self-provoked seizures. When reflex seizures are suspected, reproducing the trigger during EEG recording is fundamental; however, self-provoked seizures depend largely on the patient's will. Optimal therapy (though not always possible) consists of avoiding the trigger. Stress modifiers such as risperidone may help control self-provoked seizures.

Rett syndrome (RTT) is a neurodevelopmental disorder with one principal phenotype and several distinct, atypical variants (Zappella, early seizure onset and congenital variants). Mutations in MECP2 are found in most cases of classic RTT but at least two additional genes, CDKL5 and FOXG1, can underlie some (usually variant) cases. There is only limited correlation between genotype and phenotype. The Rett Networked Database (http://www.rettdatabasenetwork.org/) has been established to share clinical and genetic information. Through an “adaptor” process of data harmonization, a set of 293 clinical items and 16 genetic items was generated ; 62 clinical and 7 genetic items constitute the core dataset ; 23 clinical items contain longitudinal information. The database contains information on 1838 patients from 11 countries (December 2011), with or without mutations in known genes. These numbers can expand indefinitely. Data are entered by a clinician in each center who supervises accuracy. This network was constructed to make available pooled international data for the study of RTT natural history and genotype–phenotype correlation and to indicate the proportion of patients with specific clinical features and mutations. We expect that the network will serve for the recruitment of patients into clinical trials and for developing quality measures to drive up standards of medical management.

Haemolytic-Uraemic Syndrome (HUS) was first described in 1955 by Gasser (Perez del Campo et al., 2000) and defined as a multi-systemic syndrome, due to the association of microangyopathic haemolytic anemia, thrombopenia and multiorganic aggression. HUS affects mainly kidneys and leads to acute renal failure with high levels of urea and creatinin; it often involves digestive and central nervous systems. Central nervous system (CNS) lesions, typically at the basal ganglia, may also affect cortico-subcortical areas and in so doing determines motor and neurocognitive outcome, and modify the patients’ quality of life. Incidence of HUS varies among continents, highly influenced by migration movements, and it is estimated to be around 18/100,000 in children younger than 5 years old. Some countries, like Argentina and South Africa, are considered “endemic”, with a steady and relatively high incidence of HUS during all the seasons of the year; other areas, such as Canada, most of the European countries, and the west coast of the USA, are said to be “epidemic”, with sporadic cases and a lower incidence of HUS compared to Latin America and Africa during most of the year, but with self-limited relapses during summertime (Exeni, 2001). HUS etiology is diverse and physiopathologic mechanisms are not yet well known, but infective microorganisms are frequently involved, especially Escherichia coli, serotype O15:H7; this bacteria is able to produce a toxic protein (vero-toxin –VTor Shiga-toxin –Stx), which “recognizes” the endothelial cells and provokes an endothelial lesion (Scheiring, 2010). Other bacteria seem to be involved in different cases of HUS, like Salmonella enteritidis and Streptococcus pneumoniae (De Loos et al., 2002; Prestidge & Wong, 2009). Mutations in genes coding for different components of the complement system seem to be a risk factor for HUS (Skerka et al., 2009). However, the etiologic agent remains unidentified in most patients. Clinical presentation in the acute phase includes acute renal failure (100% of patients), often high blood pressure (HBP) due to a volume surcharge (35-40% of patients), and neurological

Haemolytic-uraemic syndrome (HUS) is characterized by microangiopathic hemolytic anaemia, thrombopenia and multiorganic aggression, specially renal, gastrointestinal and central nervous system disturbances. Sporadic in Spain (2/1,500,000 inhabitants), its clinical onset includes acute renal failure, hypertension and central nervous system symptoms (irritability, drowsiness, convulsions, cortical blindness, hemiparesia or coma), due to metabolic distress, hypertension or central nervous system microangiopathy. Few long-term outcome studies have been published.A retrospective analysis of a series of 58 patients with HUS between 1981 and 2006, is reported. Clinical onset, laboratory, electrophysiology, neuroimaging tests, and prognosis factors are reviewed, together with long-term clinical outcome.22 children presented neurologic symptoms, seven had some neurological test; one patient died; in five some neurological sequelae persisted (hemiparesia, cognitive deficit, visual-perception deficit), the other 16 remaining asymptomatic.Neurological morbility is high in HUS (27% of the children with neurological symptoms), with a 1.7% mortality. Seizure at onset was not a poor prognosis factor in our group. No positive correlation can be established between neuroimaging and long-term outcome.

Introduccion. El sindrome hemolitico uremico (SHU) se define como anemia hemolitica microangiopatica, trombopenia y dano multiparenquimatoso fundamentalmente renal, con frecuente afectacion digestiva y del sistema nervioso central. En Espana es esporadico (incidencia 2/1.500.000 habitantes). Las manifestaciones iniciales incluyen insuficiencia renal aguda, hipertension arterial y sintomatologia neurologica (irritabilidad, somnolencia, convulsiones, ceguera cortical, hemiparesia o coma), que puede deberse a una alteracion metabolica, hipertension arterial o microangiopatia del sistema nervioso central. Ademas del tratamiento especifico del SHU, es fundamental la valoracion y seguimiento del estado neurologico para prevenir secuelas. Existen pocas referencias bibliograficas acerca de la evolucion neurologica a largo plazo. Pacientes y metodos. Estudio retrospectivo de algunos factores relacionados con el pronostico y analisis de la evolucion neurologica a largo plazo de pacientes con SHU mediante una revision de los pacientes con SHU con manifestaciones neurologicas en fase aguda tratados en nuestro centro entre 1981 y 2006. Se analizan la clinica, analitica, estudios electrofisiologicos y neuroimagen, y su correlacion con la evolucion a medio y largo plazo. Resultados. De los 58 ninos con SHU, 22 presentaron sintomas neurologicos en fase aguda: en siete se realizo alguna exploracion complementaria neurologica; un paciente fallecio, en cinco persistio algun deficit neurologico (hemiparesia, deficit cognitivo o deficit visuoperceptivo) y 16 permanecieron asintomaticos. Conclusiones. El SHU con clinica neurologica inicial asocia una alta morbilidad (un 27% de los ninos con clinica neurologica), con mortalidad del 1,7%. Las convulsiones en la fase aguda no supusieron un factor de mal pronostico en nuestro grupo. No se puede establecer una correlacion entre los hallazgos de neuroimagen y la evolucion a largo plazo.

La Síndrome X Fràgil (SXF) és la segona causa més comuna de discapacitat intel·lectual de base genètica, per darrere de la trisomia 21, i la primera causa de discapacitat intel·lectual hereditària. En el cas dels homes, al comptar tan sols amb un cromosoma X, el fet de ser portadors de la mutació completa de el gen FMR1 provoca una absència total de la proteïna FMRP mentre que, en el cas de les dones, comporta una disminució parcial ja que el cromosoma amb el gen FMR1 sa serà capaç de sintetitzar certa quantitat de FMRP. Tot això implica que la clínica en homes sol expressar-se de forma més greu que en les dones. Aquest fet ha influït en què la gran majoria d'investigació científica s'hagi centrat en descriure el fenotip neurocognitiu dels homes afectes i que el nombre d'investigacions realitzades en dones sigui significativament inferior. La present tesi s'estructura en base a 4 articles. Aquests representen el nucli de la investigació que té com a objectius principals estudiar la relació entre diferents àrees del perfil neurocognitiu i la conducta adaptativa en noies amb el diagnòstic de SXF; així com el risc de patir assetjament escolar en el paper de víctima i la seva relació amb el seu nivell d'adaptació funcional. Tots ells compten amb una mostra de 26 noies amb SXF i 14 noies de grup control aparellades per edat i capacitat intel·lectual total, amb edats entre els 7 i els 16 anys. El Síndrome X Frágil (SXF) es la segunda causa más común de discapacidad intelectual de base genética, por detrás de la trisomía 21, y la primera causa de discapacidad intelectual hereditaria. En el caso de los varones, al contar tan solo con un cromosoma X, el hecho de ser portadores de la mutación completa del gen FMR1 provoca una ausencia total de la proteína FMRP mientras que, en el caso de las mujeres, conlleva una disminución parcial ya que el cromosoma con el gen FMR1 sano será capaz de sintetizar cierta cantidad de FMRP. Todo esto implica que la clínica en varones suele expresarse de forma más grave que en las mujeres. Este hecho ha influido en que la gran mayoría de investigación científica se haya centrado en describir el fenotipo neurocognitivo de los varones afectos y que el número de investigaciones realizadas en mujeres sea significativamente inferior. La presente tesis se estructura en base a 4 artículos. Éstos representan el núcleo de la investigación que tiene como objetivos principales estudiar la relación entre diferentes áreas del perfil neurocognitivo y la conducta adaptativa en chicas con el diagnóstico de SXF; así como el riesgo de sufrir acoso escolar en el papel de víctima y su relación con su nivel de adaptación funcional. Todos ellos cuentan con una muestra de 26 chicas con SXF y 14 chicas de grupo control emparejadas por edad y capacidad intelectual total, con edades comprendidas entre los 7 y los 16 años. Fragile X Syndrome (FXS) is the second most common cause of genetic-based intellectual disability, after trisomy 21, and the leading cause of inherited intellectual disability. In males, since they have only one X chromosome, the fact of being carriers of the complete mutation of the FMR1 gene causes a total absence of the FMRP protein while in females, it leads to a partial decrease, since the chromosome with the unaffected FMR1 gene will be able to synthesize a certain amount of FMRP. All this implies that the clinical manifestations in males tend to be more severe than in females. This has influenced the fact that the majority of scientific research has focused on describing the neurocognitive phenotype of affected males and that the number of investigations carried out in females is significantly lower. The present thesis is structured on the basis of 4 articles. These represent the core of the research whose main objectives are to study the relationship between different areas of the neurocognitive profile and adaptive behavior in girls diagnosed with FXS; as well as the risk of suffering bullying in the role of victim and its relationship with their level of functional adaptation. All of them have a sample of 26 girls with FXS and 14 girls of control group matched by age and total intellectual capacity, with ages between 7 and 16 years old. Universitat Autònoma de Barcelona. Programa de Doctorat en Psiquiatria