Weaver syndrome and EZH2 mutations: Clarifying the clinical phenotype.

Weaver syndrome, first described in 1974, is characterized by tall stature, a typical facial appearance, and variable intellectual disability. In 2011, mutations in the histone methyltransferase, EZH2, were shown to cause Weaver syndrome. To date, we have identified 48 individuals with EZH2 mutations. The mutations were primarily missense mutations occurring throughout the gene, with some clustering in the SET domain (12/48). Truncating mutations were uncommon (4/48) and only identified in the final exon, after the SET domain. Through analyses of clinical data and facial photographs of EZH2 mutation-positive individuals, we have shown that the facial features can be subtle and the clinical diagnosis of Weaver syndrome is thus challenging, especially in older individuals. However, tall stature is very common, reported in >90% of affected individuals. Intellectual disability is also common, present in ~80%, but is highly variable and frequently mild. Additional clinical features which may help in stratifying individuals to EZH2 mutation testing include camptodactyly, soft, doughy skin, umbilical hernia, and a low, hoarse cry. Considerable phenotypic overlap between Sotos and Weaver syndromes is also evident. The identification of an EZH2 mutation can therefore provide an objective means of confirming a subtle presentation of Weaver syndrome and/or distinguishing Weaver and Sotos syndromes. As mutation testing becomes increasingly accessible and larger numbers of EZH2 mutation-positive individuals are identified, knowledge of the clinical spectrum and prognostic implications of EZH2 mutations should improve.

Propionic acidemia: clinical course and outcome in 55 pediatric and adolescent patients.

BACKGROUND: Propionic acidemia is an inherited disorder caused by deficiency of propionyl-CoA carboxylase. Although it is one of the most frequent organic acidurias, information on the outcome of affected individuals is still limited. STUDY DESIGN/METHODS: Clinical and outcome data of 55 patients with propionic acidemia from 16 European metabolic centers were evaluated retrospectively. 35 patients were diagnosed by selective metabolic screening while 20 patients were identified by newborn screening. Endocrine parameters and bone age were evaluated. In addition, IQ testing was performed and the patients' and their families' quality of life was assessed. RESULTS: The vast majority of patients (>85%) presented with metabolic decompensation in the neonatal period. Asymptomatic individuals were the exception. About three quarters of the study population was mentally retarded, median IQ was 55. Apart from neurologic symptoms, complications comprised hematologic abnormalities, cardiac diseases, feeding problems and impaired growth. Most patients considered their quality of life high. However, according to the parents' point of view psychic problems were four times more common in propionic acidemia patients than in healthy controls. CONCLUSION: Our data show that the outcome of propionic acidemia is still unfavourable, in spite of improved clinical management. Many patients develop long-term complications affecting different organ systems. Impairment of neurocognitive development is of special concern. Nevertheless, self-assessment of quality of life of the patients and their parents yielded rather positive results.

New genes for focal epilepsies with speech and language disorders.

The last 2 years have seen exciting advances in the genetics of Landau-Kleffner syndrome and related disorders, encompassed within the epilepsy-aphasia spectrum (EAS). The striking finding of mutations in the N-methyl-D-aspartate (NMDA) receptor subunit gene GRIN2A as the first monogenic cause in up to 20 % of patients with EAS suggests that excitatory glutamate receptors play a key role in these disorders. Patients with GRIN2A mutations have a recognizable speech and language phenotype that may assist with diagnosis. Other molecules involved in RNA binding and cell adhesion have been implicated in EAS; copy number variations are also found. The emerging picture highlights the overlap between the genetic determinants of EAS with speech and language disorders, intellectual disability, autism spectrum disorders and more complex developmental phenotypes.

Spatial radial maze procedures and setups to dissociate local and distal relational spatial frameworks in humans.

BACKGROUND: Radial maze tasks have been used to assess optimal foraging and spatial abilities in rodents. The spatial performance was based on a capacity to rely on a configuration of local and distant cues. We adapted maze procedures assessing the relative weight of local cues and distant landmarks for arm choice in humans. NEW METHOD: The procedure allowed testing memory of places in four experimental setups: a fingertip texture-groove maze, a tactile screen maze, a virtual radial maze and a walking size maze. During training, the four reinforced positions remained fixed relative to local and distal cues. During subsequent conflict trials, these frameworks were made conflictive in the prediction of reward locations. RESULTS: Three experiments showed that the relative weight of local and distal relational cues is affected by different factors such as cues' nature, visual access to the environment, real vs. virtual environment, and gender. A fourth experiment illustrated how a walking maze can be used with people suffering intellectual disability. COMPARISON WITH EXISTING METHODS: In our procedure, long-term (reference) and short-term (working) memory can be assessed. It is the first radial task adapted to human that enables dissociating local and distal cues, to provides an indication as to their relative salience. Our mazes are moveable and easily used in limited spaces. Tasks are performed with realistic and spontaneous though controlled exploratory movements. CONCLUSION: Our tasks enabled highlighting the use of different strategies. In a clinical perspective, considering the use of compensatory strategies should orient towards adapted behavioural rehabilitation.

Evolución de la enfermería y aparición de nuevos roles: Rol de la enfermera de Cuidados Paliativos

El papel de la enfermería se ha visto sometido a muchos cambios desde sus inicios hasta la actualidad. Cambios que han ayudado a que la profesión crezca y a que se fundamente en un cuerpo de conocimientos propios. Las enfermeras, inicialmente supeditadas al estamento médico, se encuentran actualmente con un nivel de formación que les permite desarrollar su rol autónomo. Las nuevas necesidades de cuidados, generadas por los cambios socio-demográficos, epidemiológicos y políticos, y la necesidad de dar respuesta a la demanda de la población, han generado una nueva perspectiva de los sistemas de salud. Los sistemas sanitarios tratan de adaptarse a las nuevas circunstancias generando modelos sanitarios eficaces y económicamente sostenibles, donde la enfermera tiene un papel primordial. Para poder dar la atención necesaria y profesional a todo este nuevo modelo asistencial se está procediendo cada vez más y de manera más activa, a la implantación de nuevos roles enfermeros (enfermera/o gestora/or de casos, enfermera de Enlace, etc.). Dentro de estos roles, destaca el de enfermera/o en Cuidados Paliativos (CP) por su gran complejidad e incluso desconocimiento, debido a que es un rol relativamente reciente. Dada la importancia para el colectivo enfermero de conocer y comprender los cambios que ha experimentado la enfermería, el presente trabajo pretende obtener una visión general de la evolución histórica de la enfermería y la aparición de nuevos roles, profundizando en el rol de CP. Para ello se realiza una revisión de la literatura. Palabras clave: Roles enfermería, cuidado, historia enfermería, evolución enfermería, cuidados paliativos, enfermería paliativa.

A common cognitive, psychiatric, and dysmorphic phenotype in carriers of NRXN1 deletion

Deletions in the 2p16.3 region that includes the neurexin (NRXN1) gene are associated with intellectual disability and various psychiatric disorders, in particular, autism and schizophrenia. We present three unrelated patients, two adults and one child, in whom we identified an intragenic 2p16.3 deletion within the NRXN1 gene using an oligonucleotide comparative genomic hybridization array. The three patients presented dual diagnosis that consisted of mild intellectual disability and autism and bipolar disorder. Also, they all shared a dysmorphic phenotype characterized by a long face, deep set eyes, and prominent premaxilla. Genetic analysis of family members showed two inherited deletions. A comprehensive neuropsychological examination of the 2p16.3 deletion carriers revealed the same phenotype, characterized by anxiety disorder, borderline intelligence, and dysexecutive syndrome. The cognitive pattern of dysexecutive syndrome with poor working memory and reduced attention switching, mental flexibility, and verbal fluency was the same than those of the adult probands. We suggest that in addition to intellectual disability and psychiatric disease, NRXN1 deletion is a risk factor for a characteristic cognitive and dysmorphic profile. The new cognitive phenotype found in the 2p16.3 deletion carriers suggests that 2p16.3 deletions might have a wide variable expressivity instead of incomplete penetrance

The autonomic nervous activity of hostile acting

The present talk aims to examine the heart-rate variability (HRV) indexes of two populations known to be particularly sensitive to stress condition: violent offenders and intellectually impaired patients. For both, difficulties in managing stressful and emotional events could lead to unpredictable and hostile acting. Results in favour of specific HRV baseline patterns and emotional control will be developed, as the proposition of precursors of agitation in the physiological fluctuations preceding high tensed episodes. The improvement offered by coherent breathing trainings will be discussed for both groups.

La metodologia d'intervenció dels treballadors socials en el sistema de les cures pal·liatives

L’atenció a l’etapa final de la vida de les persones és un dels pilars fonamentals de les cures pal·liatives i és des de la professió del treball social que es pot promoure aquesta atenció en concepte de qualitat, tranquil·litat i preservació dels valors de les persones en situació terminal. És per aquesta raó que s’ha elaborat el present document d’investigació, el qual compta inicialment amb un recull bibliogràfic que abraçarà la metodologia d’intervenció dels treballadors socials en el sistema de les cures pal·liatives de l’Estat espanyol i del Regne Unit, país pioner en la creació de les unitats de cures pal·liatives. En aquest recull s’emmarcaran detalladament les diferències existents en termes d’intervenció i de desenvolupament d’aquest àmbit en els dos territoris. La descripció detallada dels dos models d’intervenció pretén donar la resposta a l’interrogant sobre quina és la metodologia d’intervenció que realitzen els treballadors socials en el sistema de cures pal·liatives. Per assolir aquesta resposta, s’adrecen qüestions com els objectius que lideren el treball d’aquests professionals, les funcions que realitzen en la seva pràctica professional diària i les habilitats de les que han de disposar per tal d’aconseguir que la seva intervenció sigui òptima, tant per als mateixos professionals com per a les persones amb les quals intervenen. Posteriorment a la revisió bibliogràfica, es realitzaran tres entrevistes exploratòries a tres treballadors socials de diferents nivells sanitaris que promoguin les cures pal·liatives a Catalunya. S’analitzaran les qüestions treballades en el recull bibliogràfic (objectius, funcions i habilitats dels treballadors socials), les quals permetran comparar la perspectiva teòrica cercada amb la informació primària obtinguda. Finalment, es planteja una proposta de projecte que permetrà aprofundir en la intervenció dels treballadors socials de Catalunya i del Regne Unit, realitzant una comparació entre els dos models a través de la realització de quaranta-vuit entrevistes repartides homogèniament per els dos territoris. D’aquesta manera, s’especificaran totes aquelles accions que es puguin millorar i les intervencions que siguin més òptimes per la tipologia d’atenció que es requereix en els sistemes de les cures pal·liatives d’avui en dia.

Chronic disease management programmes for adults with asthma (intervention Review)

BACKGROUND: The burden of asthma on patients and healthcare systems is substantial. Interventions have been developed to overcome difficulties in asthma management. These include chronic disease management programmes, which are more than simple patient education, encompassing a set of coherent interventions that centre on the patients' needs, encouraging the co-ordination and integration of health services provided by a variety of healthcare professionals, and emphasising patient self-management as well as patient education. OBJECTIVES: To evaluate the effectiveness of chronic disease management programmes for adults with asthma. SEARCH METHODS: Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register, MEDLINE (MEDLINE In-Process and Other Non-Indexed Citations), EMBASE, CINAHL, and PsycINFO were searched up to June 2014. We also handsearched selected journals from 2000 to 2012 and scanned reference lists of relevant reviews. SELECTION CRITERIA: We included individual or cluster-randomised controlled trials, non-randomised controlled trials, and controlled before-after studies comparing chronic disease management programmes with usual care in adults over 16 years of age with a diagnosis of asthma. The chronic disease management programmes had to satisfy at least the following five criteria: an organisational component targeting patients; an organisational component targeting healthcare professionals or the healthcare system, or both; patient education or self-management support, or both; active involvement of two or more healthcare professionals in patient care; a minimum duration of three months. DATA COLLECTION AND ANALYSIS: After an initial screen of the titles, two review authors working independently assessed the studies for eligibility and study quality; they also extracted the data. We contacted authors to obtain missing information and additional data, where necessary. We pooled results using the random-effects model and reported the pooled mean or standardised mean differences (SMDs). MAIN RESULTS: A total of 20 studies including 81,746 patients (median 129.5) were included in this review, with a follow-up ranging from 3 to more than 12 months. Patients' mean age was 42.5 years, 60% were female, and their asthma was mostly rated as moderate to severe. Overall the studies were of moderate to low methodological quality, because of limitations in their design and the wide confidence intervals for certain results.Compared with usual care, chronic disease management programmes resulted in improvements in asthma-specific quality of life (SMD 0.22, 95% confidence interval (CI) 0.08 to 0.37), asthma severity scores (SMD 0.18, 95% CI 0.05 to 0.30), and lung function tests (SMD 0.19, 95% CI 0.09 to 0.30). The data for improvement in self-efficacy scores were inconclusive (SMD 0.51, 95% CI -0.08 to 1.11). Results on hospitalisations and emergency department or unscheduled visits could not be combined in a meta-analysis because the data were too heterogeneous; results from the individual studies were inconclusive overall. Only a few studies reported results on asthma exacerbations, days off work or school, use of an action plan, and patient satisfaction. Meta-analyses could not be performed for these outcomes. AUTHORS' CONCLUSIONS: There is moderate to low quality evidence that chronic disease management programmes for adults with asthma can improve asthma-specific quality of life, asthma severity, and lung function tests. Overall, these results provide encouraging evidence of the potential effectiveness of these programmes in adults with asthma when compared with usual care. However, the optimal composition of asthma chronic disease management programmes and their added value, compared with education or self-management alone that is usually offered to patients with asthma, need further investigation.