Retrospective French nationwide survey of childhood aggressive vascular anomalies of bone, 1988-2009

<p>Abstract</p> <p>Objective</p> <p>To document the epidemiological, clinical, histological and radiological characteristics of aggressive vascular abnormalities of bone in children.</p> <p>Study design</p> <p>Correspondents of the French Society of Childhood Malignancies were asked to notify all cases of aggressive vascular abnormalities of bone diagnosed between January 1988 and September 2009.</p> <p>Results</p> <p>21 cases were identified; 62% of the patients were boys. No familial cases were observed, and the disease appeared to be sporadic. Mean age at diagnosis was 8.0 years [0.8-16.9 years]. Median follow-up was 3 years [0.3-17 years]. The main presenting signs were bone fracture (n = 4) and respiratory distress (n = 7), but more indolent onset was observed in 8 cases. Lung involvement, with lymphangiectasies and pleural effusion, was the most frequent form of extraosseous involvement (10/21). Bisphosphonates, alpha interferon and radiotherapy were used as potentially curative treatments. High-dose radiotherapy appeared to be effective on pleural effusion but caused major late sequelae, whereas antiangiogenic drugs like alpha interferon and zoledrenate have had a limited impact on the course of pulmonary complications. The impact of bisphosphonates and alpha interferon on bone lesions was also difficult to assess, owing to insufficient follow-up in most cases, but it was occasionally positive. Six deaths were observed and the overall 10-year mortality rate was about 30%. The prognosis depended mainly on pulmonary and spinal complications.</p> <p>Conclusion</p> <p>Aggressive vascular abnormalities of bone are extremely rare in childhood but are lifethreatening. The impact of anti-angiogenic drugs on pulmonary complications seems to be limited, but they may improve bone lesions.</p

Épidémiologie des infections invasives à méningocoque dans la population pédiatrique de Nouvelle-Calédonie de 2005 à 2011 et recherche de facteurs de risque

Introduction. Les infections invasives à méningoque (IIM) ont une incidence élevée en Nouvelle-Calédonie (NC). Les objectifs étaient de décrire l épidémiologie des cas pédiatriques et rechercher des facteurs de risque socio-environnementaux et/ou des déficits de l immunité innée connus pour favoriser ces infections. Matériel et Méthodes. Entre 2005 et 2011, 35 cas d IIM âgés de moins de 15 ans ont été inclus de manière retrospective selon les critères nosologiques de référence. Résultats. L incidence pédiatrique des IIM était de 2 pour cent mille habitants. La répartition par tranche d âge était inhabituelle avec une incidence faible chez les nourissons. Les cas, majoritairement mélanésiens (73%), étaient surtout originaires des Iles Loyautés (p=0,03). La proportion de sérogroupes YW135 était élevée (28%). Aucun facteur socio-environnemental n a été associé aux IIM. L étude a révélé dix cas de déficits immunitaires de la voie du complément, significativement associés aux sérogroupes rares (p=0,04). Discussion. Les particularités épidémiologiques de l étude corroboraient l hypothèse que la virulence de Neisseria Meningitidis est plus en rapport avec l hôte et son environnement que l agent infectieux lui-même. L association entre IIM et déficit en complément était retrouvée dans la littérature. Les bénéfices de l étude étaient individuels (vaccination des cas déficitaires par tétravalent) et collectif (dépistage de déficits dans les fratries). Conclusion. L impact clinique était le dépistage précoce des déficits immunitaires dans les cas d IIM afin qu ils bénéficient d une protection par tétravalent conjuguéGRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

VALUE OF TOXOPLASMA GONDII DETECTION IN ONE HUNDRED THIRTY-THREE PLACENTAS FOR THE DIAGNOSIS OF CONGENITAL TOXOPLASMOSIS.

The placenta examination by polymerase chain reaction and mouse inoculation increased the sensitivity of the diagnosis of congenital toxoplasmosis at birth from 60% (use of serologic techniques on the newborn's blood only) to 75% (both serologic techniques and placental analysis). The specificity of Toxoplasma gondii detection in the placenta was 94.7%

Characterization of six novel mutations in the CYBB gene leading to different sub-types of X-linked chronic granulomatous disease.

International audienceChronic granulomatous disease is an inherited disorder in which phagocytes lack a functional NADPH oxidase and so cannot generate superoxide anions (O(2) (-)). The most common form is caused by mutations in CYBB encoding gp91 phox, the heavy chain of flavocytochrome b(558) (XCGD). We investigated 11 male patients and their families suspected of suffering from X-linked CGD. These XCGD patients were classified as having different variants (X91(0), X91(-) or X91(+)) according to their cytochrome b(558) expression and NADPH oxidase activity. Nine patients had X91(0) CGD, one had X91(-) CGD and one had X91(+) CGD. Six mutations in CYBB were novel. Of the four new X91(0) CGD cases, three were point mutations: G65A in exon 2, G387T in exon 5 and G970T in exon 9, leading to premature stop codons at positions Try18, Try125 and Glu320, respectively, in gp91 phox. One case of X91(0) CGD originated from a new 1005G deletion detected in exon 9. Surprisingly, four nonsense mutations in exon 5 led to the generation of two mRNAs, one with a normal size containing the mutation and the other in which exon 5 had been spliced. A novel X91(-) CGD case with low gp91 phox expression was diagnosed. It was caused by an 11-bp deletion in the linking region between exon 12 and intron 12, activating a new cryptic site. Finally, a new X91(+) CGD case was detected, characterized by a missense mutation Leu505Arg in the potential NADPH-binding site of gp91 phox. No clear correlation between the severity of the clinical symptoms and the sub-type of XCGD could be established

CHANGES IN REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION–POSITIVE SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 RATES IN ADULTS AND CHILDREN ACCORDING TO THE EPIDEMIC STAGES

International audienceFrom March 2, 2020, to April 26, 2020, 52,588 reverse transcription polymerase chain reaction (RT-PCR) tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were performed in France, 6490 in children and 46,098 in adults. The rate of RT-PCR-positive SARS-CoV-2 tests for children (5.9%) was always less than that for adults (20.3%) but vary according to the epidemic stage. The risk ratio of RT-PCR-positive SARS-CoV-2 tests for adults compared with children was 3.5 (95% confidence interval: 3.2-3.9) for the whole study period

Clinical, functional and genetic analysis of twenty-four patients with chronic granulomatous disease - identification of eight novel mutations in CYBB and NCF2 genes.

International audienceChronic granulomatous disease is an inherited disorder in which phagocytes lack a functional NADPH oxidase and cannot produce superoxide anions. The most common form is caused by mutations in CYBB encoding gp91phox. We investigated 24 CGD patients and their families. Twenty-one mutations in CYBB were classified as X91(0), X91(+) or X91(-) variants according to cytochrome b (558) expression. Point mutations in encoding regions represented 50 % of the mutations found in CYBB, splice site mutations 27 %, deletions and insertions 23 %. Eight mutations in CYBB were novel leading to X91(0)CGD cases. Two of these were point mutations: c493G>T and a double mutation c625C>G in exon 6 and c1510C>T in exon 12 leading to a premature stop codon at Gly165 in gp91phox and missense mutations His209Arg/Thr503Ile respectively. Two novel splice mutations in 5'intronic regions of introns 1 and 6 were found. A novel deletion/insertion c1024_1026delCTG/insT results in a frameshift introducing a stop codon at position 346 in gp91phox. The last novel mutation was the insertion of a T at c1373 leading to a frameshift and a premature stop codon at position 484 in gp91phox. For the first time the precise size of two large mutations in CYBB was determined by array-comparative genomic hybridization and carriers' status were evaluated by multiplex ligation-dependent probe amplification assay. No clear correlation between clinical severity and CYBB mutations could be established. Of three mutations in CYBA, NCF1 and NCF2 leading to rare autosomal recessive CGD, one nonsense mutation c29G>A in exon 1 of NCF2 was new

Invasive pneumococcal disease in children can reveal a primary immunodeficiency

About 10% of pediatric patients with invasive pneumococcal disease (IPD) die from the disease. Some primary immunodeficiencies (PIDs) are known to confer predisposition to IPD. However, a systematic search for these PIDs has never been carried out in children presenting with IPD.status: publishe