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Few biomarkers for sepsis diagnosis are commonly used in neonatal sepsis. While the role of host response is increasingly recognized in sepsis pathogenesis and prognosis, there is a need for evaluating new biomarkers targeting host response in regions where sepsis burden is high and medico-economic resources are scarce. The objective of the study is to evaluate diagnostic and prognostic accuracy of biomarkers of neonatal sepsis in Sub Saharan Africa. This prospective multicentre study included newborn infants delivered in the Abomey-Calavi region in South Benin and their follow-up from birth to 3 months of age. Accuracy of transcriptional (CD74, CX3CR1), proteic (PCT, IL-6, IL-10, IP-10) biomarkers and clinical characteristics to diagnose and prognose neonatal sepsis were measured. At delivery, cord blood from all consecutive newborns were sampled and analysed, and infants were followed for a 12 weeks’ period. Five hundred and eighty-one newborns were enrolled. One hundred and seventy-two newborns developed neonatal sepsis (29.6%) and death occurred in forty-nine infants (8.4%). Although PCT, IL-6 and IP-10 levels were independently associated with sepsis diagnosis, diagnostic accuracy of clinical variables combinations was similar to combinations with biomarkers and superior to biomarkers alone. Nonetheless, CD74, being the only biomarkers independently associated with mortality, showed elevated prognosis accuracy (AUC > 0.9) either alone or in combination with other biomarkers (eg. CD74/IP-10) or clinical criterion (eg. Apgar 1, birth weight). These results suggest that cord blood PCT had a low accuracy for diagnosing early onset neonatal sepsis in Sub Saharan African neonates, while association of clinical criterion showed to be more accurate than any biomarkers taken independently. At birth, CD74, either associated with IP-10 or clinical criterion, had the best accuracy in prognosing sepsis mortality.Trial registration Clinicaltrial.gov registration number: NCT03780712. Registered 19 December 2018. Retrospectively registered.

Background: Cerebral malaria (CM) is a neuropathology which remains one of the deadliest forms of malaria among African children. The kinetics of the pathophysiological mechanisms leading to neuroinflammation and the death or survival of patients during CM are still poorly understood. The increasing production of cytokines, chemokines and other actors of the inflammatory and oxidative response by various local actors in response to neuroinflammation plays a major role during CM, participating in both the amplification of the neuroinflammation phenomenon and its resolution. In this study, we aimed to identify risk factors for CM death among specific variables of inflammatory and oxidative responses to improve our understanding of CM pathogenesis. Methods: Children presenting with CM (n = 70) due to P. falciparuminfection were included in southern Benin and divided according to the clinical outcome into 50 children who survived and 20 who died. Clinical examinationwas complemented by fundoscopic examination and extensive blood biochemical analysis associated with molecular diagnosis by multiplex PCR targeting 14 pathogens in the patients’ cerebrospinal fluid to rule out coinfections. Luminex technology and enzyme immunoassay kits were used to measure 17 plasma and 7 urinary biomarker levels, respectively. Data were analysedby univariate analysis using the nonparametric Mann‒Whitney U test and Chi2 Pearson test. Adjusted and multivariate analyses were conducted separately for plasma and urinary biomarkers to identify CM mortality risk factors. Results: Univariate analysis revealed that higher plasma levels of TNF, IL-1β, IL-10, IL-8, CXCL9, granzyme B, and angiopoietin-2 and lower urinary levels of PGEM were associated with CM mortality. The multivariate logistic analysis highlighted elevated plasma levels of IL-8 as the main risk factor for death during CM. Values obtained during follow-up at D3 and D30 revealed immune factors associated with disease resolution, including plasma CXCL5, CCL17, CCL22, and urinary 15-F2t-isoprostane. Conclusions: These results provide important insight into our understanding of CM pathogenesis and clinical outcome and may have important therapeutic implications.

Studies suggest that elevated postnatal blood lead levels (BLLs) are negatively associated with child growth. This study aimed to investigate the associations of childhood BLLs at age one year and growth outcomes at age six years (n = 661) in a cohort of children in Allada, Benin. The growth outcomes studied are weight-for-age Z-score (WAZ), height-for-age Z-score (HAZ), BMI-for-age Z-score (BMIZ), weight-for-height Z-score (WHZ), head circumference (HC), growth velocities, underweight, stunting, and wasting. Multivariable regression models examined the associations between BLLs and growth outcomes, with adjustment for potential confounders. The geometric mean BLLs was 59.3 μg/L and 82% of children had BLLs >35 μg/L at the age of 12.8 months. After adjusting for confounding factors, no overall association was found between BLL quartiles and HAZ, WAZ, BMIZ, WHZ, growth velocities, wasting, and underweight. However, boys in the highest quartile had a 1.02 cm lower HC (95% CI: [−1.81, −0.24]) as compared to the lowest quartile. Furthermore, an increased odds of being stunted was observed in children in the highest quartile of exposure compared to the first (OR: 2.43; 95% CI: [1.11–5.33]) which remained statistically significant only among girls in sex-specific strata. Blood lead was found to be associated with an increased risk of childhood stunting and a lower head circumference in a resource-limited setting.

Studies suggest that elevated postnatal blood lead levels (BLLs) are negatively associated with child growth. This study aimed to investigate associations of childhood BLLs at age one-year and growth outcomes at age six-years (n=661) in a cohort of children in Allada, Benin. The growth outcomes studied are weight-for-age Z-score (WAZ), height-for-age Z-score (HAZ) and BMI-for-age Z-score (BMIZ), head circumference (HC), underweight, stunting, and wasting. Multivariable regression models examined associations between blood lead levels, growth outcomes with adjustment for potential confounders. The geometric mean BLLs was 59.3 μg/L and 82% of children had BLLs >35 μg/L at one year. After adjusting for confounding factors, no association was found between BLLs quartiles and HAZ, WAZ, BMIZ, and height and weight growth velocities. However, boys in the highest quartile had 1.02 cm lower HC (95% CI: [-1.81, -0. 24]) as compared to those in the lowest quartile with a dose-response trend across quartiles (Ptrend =0.02). Furthermore, an increased risk of being stunted was observed in children in the highest quartile of exposure compared to the first (OR: 2.43; 95% CI: [1.11 – 5.33]) with a dose-response trend (Ptrend =0.03). Blood lead was found to be associated with an increased risk of childhood stunting and lower head circumference in a resource-limited setting.

Rural children from Benin, west Africa were evaluated with the Mullen Scales of Early Learning (MSEL) at one year of age and then at six years with the Kaufman Assessment Battery for Children (KABC...

The Plasmodium falciparum erythrocyte-membrane-protein-1 (PF3D7_1150400/PF11_0521) contains both domain cassette DC13 and DBLβ3 domain binding to EPCR and ICAM-1 receptors, respectively. This type of PfEMP1 proteins with dual binding specificity mediate specific interactions with brain micro-vessels endothelium leading to the development of cerebral malaria (CM). Using plasma collected from children at time of hospital admission and after 30 days, we study an acquisition of IgG response to PF3D7_1150400/PF11_0521 DC13 and DBLβ3_D4 recombinant constructs, and five peptides located within these constructs, specifically in DBLα1.7_D2 and DBLβ3_D4 domains. We found significant IgG responses against the entire DC13, PF11_0521_DBLβ3_D4 domain, and peptides. The responses varied against different peptides and depended on the clinical status of children. The response was stronger at day 30, and mostly did not differ between CM and uncomplicated malaria (UM) groups. Specifically, the DBLβ3 B3-34 peptide that contains essential residues involved in the interaction between PF11_0521 DBLβ3_D4 domain and ICAM-1 receptor demonstrated significant increase in reactivity to IgG1 and IgG3 antibodies at convalescence. Further, IgG reactivity in CM group at time of admission against functionally active (ICAM-1-binding) PF11_0521 DBLβ3_D4 domain was associated with protection against severe anemia. These results support development of vaccine based on the PF3D7_1150400/PF11_0521 structures to prevent CM.

Rural children from Benin, west Africa were evaluated with the Mullen Scales of Early Learning (MSEL) at one year of age and then at six years with the Kaufman Assessment Battery for Children (KABC-II), the visual computerized Tests of Variables of Attention (TOVA), and the Bruininks-Oseretsky Test (BOT-2) of motor proficiency (N = 568). Although both the MSEL and KABC-II were available to the assessors in French, instructions to the mother/child were in local language of Fon. Mothers were evaluated with the Edinburgh Postpartum Depression Scale (EPDS), Caldwell HOME Scale, educational level and literacy, and a Socio-Economic Scale - also in their local language (Fon). After adjusting for maternal factors, MSEL cognitive composite was correlated with KABC-II with moderate effect sizes, but not with TOVA scores. Overall eta-squared effect for the multivariate models were moderately to strongly correlated (.07 to .37). Neurodevelopmental assessments in early childhood adapted cross-culturally are predictive of school-age neuropsychological cognitive ability.

Lead exposure is associated with poor cognitive development in children. Very few studies in sub-Saharan Africa (SSA) have studied blood lead levels (BLLs) and non-gasoline sources of exposure in children. Data from a birth cohort in Benin (2011&ndash, 2013) suggested that 58% of 1-year-old children had BLLs &gt, 50 ug/L. We aimed to investigate the prevalence of elevated BLLs (&gt, 50 &micro, g/L and &gt, 100 &micro, g /L) among 425 of these children at 6 years of age in 2016&ndash, 2018 and to compare BLLs between age 1 and 6 years, and study sources of lead at age 6 years. BLLs were analysed by inductively coupled plasma mass spectrometry. Multiple linear regression and quantile regressions were used to study potential sources of lead. The prevalence of BLLs &gt, g/L in children was 59.5% (Geometric Mean (GM) 56.4 &micro, g/L, 95% CI: 54.1&ndash, 58.7) at 6 years of age compared to 54.8% (GM 56.5 &micro, g/L, 95% CI: 53.4&ndash, 59.6) at 1 year of age. The prevalence of children with BLLs &gt, g/L decreased from 14.4% at 1 year of age to 8.2% at 6 years of age. After adjustment for all other covariates, consumption of peanuts more than once per month was significantly associated with a 22.0% (95% CI: 4.6, 42.5) increment in BLLs at age 6 years compared with no consumption. Consumption of bushmeat killed by lead bullets at age 6 years was associated with an increase in the higher percentiles of BLLs (P75) compared with the absence of this source. Other potential sources of lead associated with BLLs with marginal significance were consumption of rice, paternal occupational exposure, and the presence of activity with the potential use of lead. This prospective cohort confirms the persistently high prevalence of elevated BLLs in children residing in a rural region in the south of Benin, as well as the presence of multiple and continuous sources of lead. These results highlight the need for prevention programs to reduce and eliminate lead exposure in children.

BACKGROUND In many developing countries, faulty complementary feeding practises and frequently contaminated foods are contributing factors to child malnutrition. The aims of this study were to evaluate the nutrition status of, and clarify the maternal safe food preparation behaviors associated with malnutrition in, children aged

Background. Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) mediates the binding and accumulation of infected erythrocytes (IE) to blood vessels and tissues. Specific interactions have been described between PfEMP1 and human endothelial proteins CD36, intercellular adhesion molecule-1 (ICAM-1), and endothelial protein C receptor (EPCR); however, cytoadhesion patterns typical for pediatric malaria syndromes and the associated PfEMP1 members are still undefined. Methods. In a cohort of 94 hospitalized children with malaria, we characterized the binding properties of IE collected on admission, and var gene transcription using quantitative polymerase chain reaction. Results. IE from patients with cerebral malaria were more likely to bind EPCR and ICAM-1 than IE from children with uncomplicated malaria (P = .007). The level of transcripts encoding CIDR alpha 1.4 and CIDR alpha 1.5 domain subclasses was higher in patients with severe disease (P

Introduction: Malaria particularly affects children in sub-Saharan African countries. This study aimed to investigate the factors associated with death in cases of severe childhood malaria to better understand the determinants of death in these children. Patients and Methods: This cohort, descriptive and analytical study was conducted from April 1 to August 15, 2015, at the CNHU-HKM pediatric clinic in Cotonou. Recruitment was exhaustive for all patients under 15 years of age who were admitted for severe malaria, as confirmed by thick smear microscopy. Results: Among the 1774 admitted patients, 449 had severe malaria caused by Plasmodium falciparum (i.e., a hospital frequency of 25.31%). The age group most affected consisted of children younger than 60 months of age (73%); female predominance was noted. The lethality rate of malaria was 13.1% (n = 59). The factors associated with death were coma (p = 0.032), poor convulsive status epilepticus (p = 0.08) and bacterial co-infection by gram negative bacteria (p = 0.021) with respectively correlations coefficient of 0.003, 3.940 and 2.424. Conclusion: Reduction of the malaria mortality rates in Benin hospitals will depend on appropriate management of poor prognostic factors, such as coma, bacterial co-infection and convulsive illness.

International audience; Background PfEMP1 is the major protein from parasitic origin involved in the pathophysiology of severe malaria, and PfEMP1 domain subtypes are associated with the infection outcome. In addition, PfEMP1 variability is endless and current publicly available protein repositories do not reflect the high diversity of the sequences of PfEMP1 proteins. The identification of PfEMP1 protein sequences expressed with samples remains challenging. The aim of our study is to identify the different PfEMP1 proteins variants expressed within patient samples, and therefore identify PfEMP1 proteins domains expressed by patients presenting uncomplicated malaria or severe malaria in malaria endemic setting in Cotonou, Benin. Methods We performed a multi-omic approach to decipher PfEMP1 expression at the patient's level in different clinical settings. Using a combination of whole genome sequencing approach and RNA sequencing, we were able to identify new PfEMP1 sequences and created a new custom protein database. This database was used for protein identification in mass spectrometry analysis. Results The differential expression analysis of RNAsequencing data shows an increased expression of the var domains transcripts DBL alpha 1.7, DBL alpha 1.1, DBL alpha 2 and DBL beta 12 in samples from patients suffering from Cerebral Malaria compared to Uncomplicated Malaria. Our approach allowed us to attribute PfEMP1 sequences to each sample and identify new peptides associated to PfEMP1 proteins in mass spectrometry. Conclusion We highlighted the diversity of the PfEMP1 sequences from field sample compared to reference sequences repositories and confirmed the validity of our approach. These findings should contribute to further vaccine development strategies based on PfEMP1 proteins.

Fetus in fetus (FIF) is an extremely rare congenital condition characterized by the parasitic development of a malformed fetal twin within a normal second twin’s body. The localization is mostly abdominal in the retroperitoneum. Thoracic localization is extremely rare. In this clinical case, a 5 month old female infant weighing 5 kg presented with a chest mass causing respiratory distress. We realized a chest CT-Scan; the latter revealed a heterogeneous mass, completely occupying the left hemithorax. Imaging studies confirmed the presence of the fetus in fetus occupying the entire left hemithorax and mediastinum, pushing the heart to the right. A complete resection of the mass could be performed under general anesthesia and orotracheal intubation (GA + OTI). The monitoring involved ECG, SpO2, NIBP, PR, T°, and Capnometry. The ventilation was first mechanical and secondarily manual. The patient did not receive unipulmonary ventilation nor central IV line. Postoperative period marked by volume overload, anemia, cardiac arrest, with successful resuscitation. Histopathology studies and imaging confirmed the diagnosis. On D9, she was discharged from pediatric critical care and from hospital on day ten postoperative. She presented in good clinical condition after a 3-month follow-up. We report this case in order to show how we took care of this FIF case in the precarious conditions.

IntroductionNeonatal sepsis outreaches all causes of neonatal mortality worldwide and remains a major societal burden in low and middle income countries. In addition to limited resources, endemic morbidities, such as malaria and prematurity, predispose neonates and infants to invasive infection by altering neonatal immune response to pathogens. Nevertheless, thoughtful epidemiological, diagnostic and immunological evaluation of neonatal sepsis and the impact of gestational malaria have never been performed.Methods and analysisA prospective longitudinal multicentre follow-up of 580 infants from birth to 3 months of age in urban and suburban Benin will be performed. At delivery, and every other week, all children will be examined and clinically evaluated for occurrence of sepsis. At delivery, cord blood systematic analysis of selected plasma and transcriptomic biomarkers (procalcitonin, interleukin (IL)-6, IL-10, IP10, CD74 and CX3CR1) associated with sepsis pathophysiology will be evaluated in all live births as well as during the follow-up, and when sepsis will be suspected. In addition, whole blood response to selected innate stimuli and extensive peripheral blood mononuclear cells phenotypic characterisation will be performed. Reference intervals specific to sub-Saharan neonates will be determined from this cohort and biomarkers performances for neonatal sepsis diagnosis and prognosis tested.Ethics and disseminationEthical approval has been obtained from the Comité d’Ethique de la Recherche – Institut des Sciences Biomédicales Appliquées (CER-ISBA 85 - 5 April 2016, extended on 3 February 2017). Results will be disseminated through international presentations at scientific meetings and publications in peer-reviewed journals.Trial registration numberClinicalTrials.gov registration number: NCT03780712.

PfEMP1 are the major protein family from parasitic origin involves in the pathophysiology of severe malaria, and PfEMP1 domain subtypes are associated with the infection outcome. In addition, PfEMP1 variability in endless and current protein repository do not reflect the immense diversity of the sequences of PfEMP1 proteins. The aim of our study was to identify the different PfEMP1 variants expressed within a patient sample by mass spectrometry. We performed a proteogenomic approach to decipher at the patient’s level PfEMP1 expression in different clinical settings: cerebral malaria, severe anemia and uncomplicated malaria. The combination of whole genome sequencing approach, RNAsequencing, and mass spectrometry proteomic analysis allowed to attribute PfEMP1 sequences to each sample and classify the relative expression level of PfEMP1 proteins within each sample. We predicted PfEMP1 structures using the newly identified protein sequences. We confirmed the involvement of DBLβ in malaria pathogenesis and observed that CIDRα domains linked to ICAM-1 binding DBLβ domains displayed EPCR binding structure.

Objectives The consequences of varicocele can be dramatic, with reproduction difficulties. This survey aimed to determine the prevalence of varicocele among schoolboys at Cotonou and describe its clinical aspects. Patients and methods This prospective and analytical study, complying with all ethical requirements, was conducted from 1 February to 31 August 2012 on schoolboys of secondary schools in Cotonou who were aged between 10 and 19 years. The data collected included information on sociodemographic characteristics such as age and ethnicity and clinical aspect symptoms such as history, physical signs, level of sexual maturity, grade of varicocele, testicular volume, and associated anomalies. Results The prevalence of varicocele was 5.47% (149/2724). The ages of boys with varicocele ranged between 12 and 19 years (mean age 16.50± 2.03 years). The peak prevalence of varicocele was 18 years and it varied significantly with age, ethnicity, and level of sexual development. Varicocele was symptomatic in only 28.86% of cases. The associated symptoms were scrotal weight (17.44%) and scrotal pain (14.77%), and these occurred mainly during football or intense physical effort (36.91%). Family history was remarkable in some cases. This pathology was mainly located at the left (76.51%). On the basis of the Amelar and Dublin classification, varicoceles were of grades 1, 2, and 3, respectively, in 2.25, 2.56, and 0.97% of cases. Left testicular hypotrophy was clinically noticed in 34.90% of boys affected by varicocele but with respect to severity. Conclusion More attention should be given to this issueby establishing a nationwide program of detection and treatment of varicocele in schools. Keywords : adolescents, epidemiologic clinical aspects, varicocele

Studies on the health benefits of exclusive breastfeeding (EBF) and susceptibility to malaria have shown contradictory results. These studies often failed to account for dose response effects. The deuterium dilution technique was used to evaluate the breastmilk intake, the amount of water from sources other than human milk and the exclusivity of breastfeeding. We determine Plasmodium falciparum parasitaemia prevalence in children aged less than six month according to their breastfeeding regimen and maternal milk dose ingested in southern Benin. We conducted a cross sectional study in the Ouidah Kpomasse Tori-Bossito (OKT) health zone in southern Benin from February to December 2014, an intense transmission season. 115 mothers paired with their children aged from 0 to 6 months were enrolled. The daily human milk was measured through saliva of each mother and child pair (MCP) over a period of 14 days by the technique of deuterium oxide "dose to the mother" using the Fourier Transformed Infrared Spectrometer (FTIR). Malaria parasitaemia in children was determined by quantitative Polymerase Chain Reaction (qPCR) in real time at day 14 and day 28. The average age was 2.3 months. The distribution of Plasmodium falciparum parasitaemia in children was 0.00%, 5.08% and 3.85% respectively in exclusive, predominant and partial breastfeeding regimens. The mean intake of breast milk was 641.71 mL per day; 256.75 mL of water per day was taken from sources other than breastmilk. Adjusted linear regression analysis revealed a significant association between quantity of breastmilk and parasitaemia prevalence; infected children (qPCR positive) had 164.11 mL of ingested breastmilk per day less than children without parasitaemia (p=0.00). Our findings highlighted the association between the low risk of Plasmodium falciparum parasitaemia and the ingested breastmilk dose. Study with larger numbers of patients would be necessary to confirm this relationship.

Introduction: Mortality in Down syndrome (DS) remain high and often in relation with visceral malformations. The aim of this work was to describe the congenital visceral malformations associated with DS in children followed in the pediatric unit of National Health Teaching Hospital of Cotonou, in order to improve their management.Patients and methods: It was a prospective and descriptive survey conducted on children who were treated for DS at the pediatric unit of the National Health Teaching Hospital of Cotonou from October 2015 through July 2016. All children had a diagnosis of DS based on karyotype with trisomy 21 and underwent heart, gastrointestinal and kidney ultrasonographies.Results: A total of 36 children were included. The sex ratio was 1.25 and infants under 12 months were the most represented age group (55.56 %). The mean age at diagnosis was 18.8 months. The majority of mothers were aged than 35 years. Clinical features were dominated by up slanting palpebral fissures and hypertelorism. The visceral malformations were observed only in heart with a frequency of 55.55%. Atrio-ventricular septal defect (27.78%) and patent ductus arteriosus (16.76%) were predominant. Nondisjunction trisomy 21 was found in all children.Conclusion: Congenital visceral malformations associated to DS in children at pediatric unit of the National Health Teaching Hospital of Cotonou were exclusively cardiac with atrioventricular septal defect as major type. Early diagnosis of DS with malformations screening are essential for better management of affected children.

Plasmodium falciparum is responsible of severe malaria, including cerebral malaria (CM). During its intra-erythrocytic maturation, parasite-derived proteins are expressed, exported and presented at the infected erythrocyte membrane. To identify new CM-specific parasite membrane proteins, we conducted a mass spectrometry-based proteomic study and compared the protein expression profiles between 9 CM and 10 uncomplicated malaria (UM) samples. Among the 1097 Plasmodium proteins identified, we focused on the 499 membrane-associated and hypothetical proteins for comparative analysis. Filter-based feature selection methods combined with supervised data analysis identified a subset of 29 proteins distinguishing CM and UM samples with high classification accuracy. A hierarchical clustering analysis of these 29 proteins based on the similarity of their expression profiles revealed two clusters of 15 and 14 proteins, respectively under- and over-expressed in CM. Among the over-expressed proteins, the MESA protein is expressed at the erythrocyte membrane, involved in proteins trafficking and in the export of variant surface antigens (VSAs), but without antigenic function. Antigen 332 protein is exported at the erythrocyte, also involved in protein trafficking and in VSAs export and exposed to the immune system. Our proteomics data demonstrate an association of selected proteins in the pathophysiology of CM.

Resume Objectif Dans la plupart des salles de naissance d'Afrique, il est souvent interdit aux femmes d'adopter une position vertical edurant le travail et l'accouchement. L'objectif de cette etude est de determiner l'effet de la position libre verticale (debout, assise, accroupie), comparativement a la position classique de decubitus dorsal, sur le deroulement de l'accouchement et les issues perinatales et maternelles incluant la satisfaction des meres. Methodologie Nous avons compare un groupe de 490 parturientes ayant choisi d'accoucher en position libre verticale a 490 femmes accouchees en position classique, a l'Hopital de la mere et de l'enfant Lagune de Cotonou, du 1 er janvier 2009 au 31 decembre 2011. Les variables examinees sont la duree du travail, le type d'accouchement, la frequence d'episiotomie, les indices de bien-etre fœtal et neonatal (rythme cardiaque fœtal, Apgar, reanimation) et les issues postnatales maternelles (dechirures perineales, complications hemorragiques), y compris la satisfaction maternelle. L'analyse descriptive englobe des comparaisons entre les deux groupes. Resultats Les deux groupes ont un âge maternel (25 ans) et gestationnel (39 semaines) similaire. Le groupe du choix de la position se distingue par un plus grand nombre de nullipares (53 % contre 40 %, P Conclusion La position verticale libre semble une option efficace et securitaire pour le deroulement du travail et de l'accouchement, et elle est plus satisfaisante pour les meres.

International audience; Oculo-dento-digital dysplasia (ODDD) is an autosomal dominant disorder with complete penetrance and high intra- and interfamilial phenotypic variability. The key features in this syndrome are microphthalmia, enamel hypoplasia and syndactyly of the 4th-5th fingers. ODDD is caused by mutations in the connexin 43 gene (GJA1). We report here four patients from three families with GJA1 mutations, one of them diagnosed prenatally. The three mutations (c.52T > C/p.Ser18Pro, c.689_690delTA/p.Tyr230CysfsX6, c.442C > G/p.Arg148Gly) have been reported once before. Two patients had white matter hypersignal anomalies, associated in one case with mental retardation, but asymptomatic in the other one, an observation that leads us to discuss systematic neuroradiological imaging for ODDD. One case has optic atrophy, another has hypospadias. The patient carrying a truncating mutation of Cx43 did not have palmoplantar keratoderma, in contradiction with the previously suggested genotype-phenotype correlation between truncating mutation and skin involvement.

Background: The diagnosis of varicocèle is clinical. In order to improve diagnosis of varicocele, we compared the clinical with the ultrasound findings in schoolboys with the condition. This is because the conditions can affect testicular growth. Patients and Methods: It was a cross-sectional, descriptive study of schoolboys aged from 10 to 19 years who had varicocele. Among 2724 boys examined, 149 had varicocele and only 81 had scrotal (18 with Doppler) and renal ultrasound examination. Results: Among the 81 adolescents who were clinically diagnosed with varicocele and also with the aid of ultrasound scan, 25, 36 and 20 had grade 1, 2 and 3, respectively. Testicular hypotrophy (TH) was clinically noticed in 17 cases. At ultrasonography, varicocele was bilateral in 87.66% and unilateral in 12.34% (P = 0.01) with 32 adolescents (39.51%) showing TH compared with 20.99% being diagnosed with TH using clinical examination alone (P = 0.01). In 50 schoolboys (61.73%) with unilateral varicocele, a subclinical type was discovered at other side. Renal ultrasound revealed abnormalities in 4.93% of cases. Doppler ultrasound helped in finding varicoceles along the top edge of the testis (n = 15) and under tunica albuginea (n = 3). Conclusion: TH due to varicocele is better studied by ultrasound.

In most of Africa's birthing units, women are often forbidden to stand during labour and delivery. This study aimed to determine the effect of a freely vertical position (standing,sitting, crouching) compared with the traditional supine position on the course of delivery and on perinatal and maternal outcomes(including the satisfaction level of mothers).Methods: We compared a group of 490 women who chose to deliver in a freely vertical position with 490 women who delivered in a traditional position, at the Hopital de Ia mere et de l'enfant Lagune of Cotonou, from January 1, 2009, to December 31,2011. Variables studied include length of labour, type of delivery,frequency of episiotomy, fetal and neonatal well-being indices(fetal heart rate, Apgar score, resuscitation), and postnatal maternal outcomes (perineal tears, hemorrhagic complications),including maternal satisfaction. Descriptive analysis includes comparisons between those two groups.Results: Both groups had similar maternal (25 years old) and gestational (39 weeks) ages. The "Choice of position" group had a greater number of nulliparous women (53% vs. 40%,P0.001) and a higher educational level (high-school diploma and postgraduate training: 77.5% vs. 45.1 %; P0.001 ). The average length of the active phase was shortened by 20 minutes in women who freely chose their delivery position (P0.01 ).Moreover, these women experienced spontaneous delivery in higher numbers, with 10 times fewer assisted deliveries (0.4%vs. 4.3%; P0.01) and two times fewer episiotomy interventions(3.5% vs. 8.0%; P0.01) than their counterparts. When women freely choose their delivery position, there are close to three times fewer cases of fetal heart rate anomalies and meconium liquor (2.9% vs. 8.9%; P0.01 and 0.4% vs. 1.4%; P0.01 ).Perineal and cervical tears are rare and occur in similar numbers in both groups, and the same can be said of cases of postpartum hemorrhage. The number of satisfied mothers is higher in the"Choice of position" group (87.0% vs. 61.2%; P0.01 ).Conclusion: The choice of a freely vertical position seems to be an efficient and safe option during labour and delivery, and is more satisfying for mothers.

Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare autosomal dominant disorder whose main features are the abnormal shape, position and alignment of the eyelids. Type I refers to BPES with female infertility from premature ovarian failure while type II is limited to the ocular features. A causative gene, FOXL2, has been localized to 3q23. We report a black female who carried a de novo chromosomal translocation and 3.13 Mb deletion at 3q23, 1.2 Mb 5' to FOXL2. This suggests the presence of distant cis regulatory elements at the extended FOXL2 locus. In spite of 21 protein coding genes in the 3.13 Mb deleted segment, the patient had no other malformation and a strictly normal psychomotor development at age 2.5 years. Our observation confirms panethnicity of BPES and adds to the knowledge of the complex cis regulation of human FOXL2 gene expression.

Disability is an umbrella term, covering impairments, activity limitations, and participation restrictions. Impairment is a problem in body function or structure; an activity limitation is a difficulty encountered by an individual in executing a task or action; while a participation restriction is a problem experienced by an individual in involvement in life situations. Thus disability is a complex phenomenon, reflecting an interaction between features of a person’s body and features of the society in which he or she lives (WHO, 2011). This issue is so important that World Health Organization (WHO) and World Bank Group command a report on it (WHO, 2011). People who experience mental health conditions or intellectual impairments appear to be more disadvantaged in many settings than those who experience physical or sensory impairments. Prevalence of children with disabilities vary substantially depending on the definition and measure of disability. Available data suggests that 93 million (5.1%) children aged 0–14 years have moderate or severe disability” (WHO, 2011). This matter is poorly addressed in Africa especially in sub Sahara region. We present here childhood intellectual and developmental disability management in an African setting. We will cover in this prospective survey, diagnosis tools regarding the clinical practices (clinical examination, psychomotor evaluation) with contribution from pediatricians, specialists of psychiatrics and neurologists; laboratory investigations with insight on South-North collaboration in medical genetics sector (cytogenetics and molecular biology); main etiologies; management; social considerations and perspectives in intellectual and developmental disability management in Benin and in West African sub region.

Management of Children with Intellectual and Developmental Disability in an African Setting

International audience; Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by selective degeneration of motoneurones. Familial ALS is an age-dependent autosomal dominant disorder in which mutations in the homodimeric enzyme Cu/Zn superoxide dismutase 1 (SOD1) is linked to the disease. An animal model for this disease is a transgenic mouse expressing the mutated human SOD1(G93A) gene. Recent electrophysiological data emphasised that the striking selective vulnerability of motoneurones might be due to their differential calcium buffering capacities. Therefore we have investigated, using immunohistochemistry, the expression of different calcium binding proteins in brainstem and spinal cord from normal and SOD1 mutated mice. Among the 13 calcium-binding proteins screened, only one, S100A6, a homodimeric calcium-binding protein able to bind four Zn(2+), appeared to be highly expressed in the SOD1 mutated mice. In brainstem, reactive astrocytes, but not motoneurones, from several regions, including nerve 12 root, were highly S100A6-positive. Hypoglossal nucleus was negative for S100A6. In dorsal root, reactive astrocytes from both white matter and anterior horn were highly reactive. If overexpression of S100A6 is specific for ALS, it will be a valuable diagnostic marker for this disease.