Mowat-Wilson syndrome

Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome characterized by a distinct facial phenotype (high forehead, frontal bossing, large eyebrows, medially flaring and sparse in the middle part, hypertelorism, deep set but large eyes, large and uplifted ear lobes, with a central depression, saddle nose with prominent rounded nasal tip, prominent columella, open mouth, with M-shaped upper lip, frequent smiling, and a prominent but narrow and triangular pointed chin), moderate-to-severe intellectual deficiency, epilepsy and variable congenital malformations including Hirschsprung disease (HSCR), genitourinary anomalies (in particular hypospadias in males), congenital heart defects, agenesis of the corpus callosum and eye anomalies. The prevalence of MWS is currently unknown, but 171 patients have been reported so far. It seems probable that MWS is under-diagnosed, particularly in patients without HSCR. MWS is caused by heterozygous mutations or deletions in the Zinc finger E-box-binding homeobox 2 gene, ZEB2, previously called ZFHX1B (SIP1). To date, over 100 deletions/mutations have been reported in patients with a typical phenotype; they are frequently whole gene deletions or truncating mutations, suggesting that haploinsufficiency is the main pathological mechanism. Studies of genotype-phenotype analysis show that facial gestalt and delayed psychomotor development are constant clinical features, while the frequent and severe congenital malformations are variable. In a small number of patients, unusual mutations can lead to an atypical phenotype. The facial phenotype is particularly important for the initial clinical diagnosis and provides the hallmark warranting ZEB2 mutational analysis, even in the absence of HSCR. The majority of MWS cases reported so far were sporadic, therefore the recurrence risk is low. Nevertheless, rare cases of sibling recurrence have been observed. Congenital malformations and seizures require precocious clinical investigation with intervention of several specialists (including neonatologists and pediatricians). Psychomotor development is delayed in all patients, therefore rehabilitation (physical therapy, psychomotor and speech therapy) should be started as soon as possible

Phenotype and genotype of 87 patients with Mowat-Wilson syndrome and recommendations for care

Mowat-Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype-phenotype correlations of MWS.MethodsIn a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations.ResultsAll anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluation of MWS to date, we define its clinical evolution occurring with age and derive suggestions for patient management. Furthermore, we observe that its severity correlates with the kind of ZEB2 variation involved, ranging from ZEB2 locus deletions, associated with severe phenotypes, to rare nonmissense intragenic mutations predicted to preserve some ZEB2 protein functionality, accompanying milder clinical presentations.ConclusionKnowledge of the phenotypic spectrum of MWS and its correlation with the genotype will improve its detection rate and the prediction of its features, thus improving patient care.GENETICS in MEDICINE advance online publication, 4 January 2018; doi:10.1038/gim.2017.221

Single Market and Single Currency: Intended and Unintended Effects

International audienceFor those who supported the project of creating a single currency, monetary union was seen as the completion of economic integration and of the Single Market. This combination was expected to boost economic growth and foster economic convergence among EU economies. It has led to a significant intensification of economic and financial integration: trade in goods and services has increased, cross-border provision of services and labor commuting too; labor and capital have also become more mobile. But for the lack of significant progress in political integration and collective decision-making, member state governments have been prone to resort to tax competition and other non-cooperative strategies. Although this has tended to increase economic inequalities and asymmetries among EU member states, the outlook for more cooperative strategies is now mixed: tensions tend to exacerbate and public opinions are expecting collective action, but agreement on common policies is made more difficult by existing differences in economic situations and performance

Pain management after laminectomy: a systematic review and procedure-specific post-operative pain management (prospect) recommendations

International audiencePURPOSE: With lumbar laminectomy increasingly being performed on an outpatient basis, optimal pain management is critical to avoid post-operative delay in discharge and readmission. The aim of this review was to evaluate the available literature and develop recommendations for optimal pain management after one- or two-level lumbar laminectomy. METHODS: A systematic review utilizing the PROcedure-SPECific Post-operative Pain ManagemenT (PROSPECT) methodology was undertaken. Randomised controlled trials (RCTs) published in the English language from 1 January 2008 until 31 March 2020-assessing post-operative pain using analgesic, anaesthetic and surgical interventions-were identified from MEDLINE, EMBASE and Cochrane Databases. RESULTS: Out of 65 eligible studies identified, 39 RCTs met the inclusion criteria. The analgesic regimen for lumbar laminectomy should include paracetamol and a non-steroidal anti-inflammatory drug (NSAID) or cyclooxygenase (COX)-2 selective inhibitor administered preoperatively or intraoperatively and continued post-operatively, with post-operative opioids for rescue analgesia. In addition, surgical wound instillation or infiltration with local anaesthetics prior to wound closure is recommended. Some interventions-gabapentinoids and intrathecal opioid administration-although effective, carry significant risks and consequently were omitted from the recommendations. Other interventions were also not recommended because there was insufficient, inconsistent or lack of evidence. CONCLUSION: Perioperative pain management for lumbar laminectomy should include paracetamol and NSAID- or COX-2-specific inhibitor, continued into the post-operative period, as well as intraoperative surgical wound instillation or infiltration. Opioids should be used as rescue medication post-operatively. Future studies are necessary to evaluate the efficacy of our recommendations