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Although the prognosis of CHARGE syndrome can be highly variable from mild until severe, final diagnosis is difficult to establish in utero. The aim of our study is to compare antenatal and postnatal findings in a retrospective cohort of 10 successive patients with a positive CHD7 gene variant in order to identify the specific prenatal features for CHARGE syndrome diagnosis. Fetal ultrasound, follow-up and supplementary investigations are collected and compared to postnatal findings. Congenital heart defect (7/10), choanal atresia (7/10) and tracheoesophageal atresia (4/10) are the most frequent fetal anomalies found. Inner and external ear anomalies appear as the keystone (constant features) for prenatal diagnosis of CHARGE syndrome in fetuses with multiple anomalies and normal microarray karyotype. External ear malformations are identified in all cases by 3D ultrasound when carefully evaluated. MRI and temporal bone CT-Scan are second line useful tools to assess the diagnosis when looking for semicircular canal agenesis, arhinencephaly and/or choanal atresia. Before availability of prenatal exome sequencing in clinical routine, present findings lead to the recommendation that fetuses, with congenital heart defect (mainly septal and conotruncal), cleft lip/palate or unexplained polyhydramnios should carefully be screened for clues suggesting CHARGE syndrome using 2D and 3D ultrasound, MRI and temporal bone CT-Scan. When CHARGE syndrome is suspected with normal molecular karyotype, CHD7 gene sequencing must be offered.

“Serpentine-like syndrome” is a severe and rare association of multiple congenital malformations, characterised by brachioesophagus, secondary intrathoracic stomach, and vertebral anomalies. Other associated anomalies have been described, such as malposition and herniation of abdominal organs. We report the natural history of a baby girl born at 29 weeks of gestation with intra uterine growth restriction, short neck, large rachischisis from cervical to thoracic spine, a very short oesophagus, thoracic stomach associated with a midline diaphragmatic hernia, malrotated gut and median cleft lip. Most of these anomalies were detected antenatally. Molecular karyotype was normal. She died at age 12 days. To our knowledge, the present patient represents the 8th report of a case of “Serpentine-like syndrome”. Brachioesophagus and congenital vertebral anomalies, in particular rachischisis, are the cardinal features of this condition. All reported cases have been sporadic and the cause is still unknown. We believe that the specificity of the presentation as well as the similarities between available descriptions of patients suggests a common, yet to identify, molecular cause, possibly involving a developmental “toolkit”/homeobox gene or related pathways.

Malformations of cortical development (MCD) represent a large group of brain cortical anomalies characterized by distinctive MRI findings. This 'radiologically-based' classification required re evaluation over time on identified underlying mechanisms (cytogenetic and/or molecular). The understanding of genotype findings (nature of cytogenetic/molecular mutation, cellular pathways consequences, timing, …) draw line of evidence on these distinctive group of conditions whereas sometimes precise and constant recurrent genotype/phenotype correlation may not be present. The clinical diagnosis of MCD is often difficult due to variability and rarity of individual types of malformations. Recent studies have established a relationship between lissencephaly and pathogenic variants in genes involved in the kinesin/tubulin pathways, as the KIF5C gene. Pathogenic variants in the KIF5C gene are a more recently discovered cause of severe developmental delay with epilepsy, characterized by specific malformation of cortical development such as pachygyria. Only seven children have been described to date. We report the natural history of a sixteen years old patient identified carrier of a KIF5C gene mutation who developed infantile epilepsy. We then gather phenotype description and molecular results of all reported patients so far in order to better define this entity.

Copyright © 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited, Regenerative medicine using stem cell technology is an emerging field that is currently tested for inborn and acquired liver diseases. Objective. This phase I/II prospective, open label, multicenter, randomized trial aimed primarily at evaluating the safety of Heterologous Human Adult Liver–derived Progenitor Cells (HepaStem) in pediatric patients with urea cycle disorders (UCDs) or Crigler-Najjar (CN) syndrome 6 months posttransplantation. The secondary objective included the assessment of safety up to 12 months postinfusion and of preliminary efficacy. Methods. Fourteen patients with UCDs and 6 with CN syndrome were divided into 3 cohorts by body weight and intraportally infused with 3 doses of HepaStem. Clinical status, portal vein hemodynamics, morphology of the liver, de novo detection of circulating anti– human leukocyte antigen antibodies, and clinically significant adverse events (AEs) and serious adverse events to infusion were evaluated by using an intent-to-treat analysis. Results. The overall safety of HepaStem was confirmed. For the entire study period, patient-month incidence rate was 1.76 for the AEs and 0.21 for the serious adverse events, of which 38% occurred within 1 month postinfusion. There was a trend of higher events in UCD as compared with CN patients. Segmental left portal vein thrombosis occurred in 1 patient and intraluminal local transient thrombus in a second patient. The other AEs were in line with expectations for catheter placement, cell infusion, concomitant medications, age, and underlying diseases. Conclusions. This study led to European clinical trial authorization for a phase II study in a homogeneous patient cohort, with repeated infusions and intermediate doses.

OBJECTIVES: Cirrhotic children wait-listed for liver transplant are prone to bleeding from gastrointestinal varices. Grade 2-3 esophageal varices, red signs, and gastric varices are well-known risk factors. However, the involvement of hemostatic factors remains controversial because of the rebalanced state of coagulation during cirrhosis. METHODS: Children suffering from decompensated cirrhosis were prospectively included while being on waitlist. Portal hypertension was assessed by ultrasound and endoscopy. Coagulopathy was evaluated through conventional tests, thromboelastometry, and platelet function testing. The included children were followed up until liver transplantation, and all bleeding episodes were recorded. Children with or without bleeding were compared according to clinical, radiological, endoscopic, and biological parameters. In addition, validation of a predictive model for risk of variceal bleeding comprising of grade 2-3 esophageal varices, red spots, and fibrinogen level

Background Extensive and complex vascular malformations often cause chronic pain and severe functional restraint. Conventional treatments, such as surgery and/or sclerotherapy, are rarely curative, underscoring the great need for new therapeutic modalities. Recent preclinical and clinical data demonstrated that sirolimus could offset the progression of vascular malformations and significantly improve quality of life of patients through inhibition of the Phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian Target of Rapamycin (mTOR) pathway. The purpose of this prospective study was to assess the efficacy and safety of this treatment in patients with extensive or complex slow-flow vascular malformations. Methods Sirolimus was administered orally on a continuous dosing schedule with pharmacokinetic-guided target serum concentration level of 10 to 15 ng/ml. Patients were seen every month for the first three months and subsequently every three months. The primary endpoints were safety and efficacy, based on clinical, biological and radiological evaluations, as well as a quality of life questionnaire. Results Nineteen patients, from 3 to 64 years old, with lymphatic (LM), venous (VM) or complex slow-flow malformations, refractory to standard care, were enrolled and received sirolimus continuously. After 12 months of follow-up, 16 patients were available for assessment of efficacy and safety: all had a significant and rapid improvement of their symptoms and quality of life. In two patients, sirolimus treatment permitted sclerotherapy and surgery, initially evaluated unfeasible. Sirolimus was well tolerated, with mucositis as the most common (10% of patients) grade 3 adverse event. Conclusions Sirolimus was efficient in extensive LM, VM and/or complex malformations that were refractory to conventional treatments and was well tolerated.

International audience; Mutations in the oligophrenin 1 gene (OPHN1) have been identified in patients with X-linked intellectual disability (XLID) associated with cerebellar hypoplasia and ventriculomegaly, suggesting it could be a recognizable syndromic intellectual disability (ID). Affected individuals share additional clinical features including speech delay, seizures, strabismus, behavioral difficulties, and slight facial dysmorphism. OPHN1 is located in Xq12 and encodes a Rho-GTPase-activating protein involved in the regulation of the G-protein cycle. Rho protein members play an important role in dendritic growth and in plasticity of excitatory synapses. Here we report on 17 individuals from four unrelated families affected by mild to severe intellectual disability due to OPHN1 mutations without cerebellar anomaly on brain MRI. We describe clinical, genetic and neuroimaging data of affected patients. Among the identified OPHN1 mutations, we report for the first time a missense mutation occurring in a mosaic state. We discuss the intrafamilial clinical variability of the disease and compare our patients with those previously reported. We emphasize the power of next generation techniques (X-exome sequencing, whole-exome sequencing and targeted multi-gene panel) to expand the phenotypic and mutational spectrum of OPHN1-related ID.

We herein report the case of a 3-year-old girl with atypical congenital right upper limb lymphedema who developed an angiosarcoma. Only a few cases have been reported following congenital form of lymphedema and only 4 in such a young child. We also summarize all cases of angiosarcoma associated with congenital lymphedema reported in the literature., info:eu-repo/semantics/published

To evaluate the outcome of pediatric living donor liver transplantation (LDLT) regarding portal vein (PV) reconstruction, ABO compatibility, and impact of maternal donation on graft acceptance.LDLT and ABO-mismatched transplantation constitute feasible options to alleviate organ shortage in children. Vascular complications of portal hypoplasia in biliary atresia (BA) and acute rejection (AR) are still major concerns in this field.Data from 250 pediatric LDLT recipients, performed at Cliniques Universitaires Saint-Luc between July 1993 and June 2012, were collected retrospectively. Results were analyzed according to ABO matching and PV complications. Uni- and multivariate analyses were performed to study the impact of immunosuppression, sex matching, and maternal donation on AR rate.Overall, the 10-year patient survival rate was 93.2%. Neither patient or graft loss nor vascular rejection, nor hemolysis, was encountered in the ABO nonidentical patients (n = 58), provided pretransplant levels of relevant isoagglutinins were below 1/16. In BA recipients, the rate of PV complications was lower after portoplasty (4.6%) than after truncal PV anastomosis (9.8%) and to jump graft interposition (26.9%; P = 0.027). In parental donation, maternal grafts were associated with higher 1-year AR-free survival (55.2%) than paternal grafts (39.8%; P = 0.041), but only in BA patients.LDLT, including ABO-mismatched transplantation, constitutes a safe and efficient therapy for liver failure in children. In BA patients with PV hypoplasia, portoplasty seems to constitute the best technique for PV reconstruction. Maternal donation might be a protective factor for AR.

Capillary malformation-arteriovenous malformation (CM-AVM) is an autosomal-dominant disorder, caused by heterozygous RASA1 mutations, and manifesting multifocal CMs and high risk for fast-flow lesions. A limited number of patients have been reported, raising the question of the phenotypic borders. We identified new patients with a clinical diagnosis of CM-AVM, and patients with overlapping phenotypes. RASA1 was screened in 261 index patients with: CM-AVM (n=100), common CM(s) (port-wine stain; n=100), Sturge-Weber syndrome (n=37), or isolated AVM(s) (n=24). Fifty-eight distinct RASA1 mutations (43 novel) were identified in 68 index patients with CM-AVM and none in patients with other phenotypes. A novel clinical feature was identified: cutaneous zones of numerous small white pale halos with a central red spot. An additional question addressed in this study was the second-hit hypothesis as a pathophysiological mechanism for CM-AVM. One tissue from a patient with a germline RASA1 mutation was available. The analysis of the tissue showed loss of the wild-type RASA1 allele. In conclusion, mutations in RASA1 underscore the specific CM-AVM phenotype and the clinical diagnosis is based on identifying the characteristic CMs. The high incidence of fast-flow lesions warrants careful clinical and radiologic examination, and regular follow-up. (C) 2013 Wiley Periodicals, Inc.

WOS: 000372165300007 PubMed ID: 26951490 Spondyloenchondrodysplasia is a rare immuno-osseous dysplasia caused by biallelic mutations in ACP5. We aimed to provide a survey of the skeletal, neurological and immune manifestations of this disease in a cohort of molecularly confirmed cases. We compiled clinical, genetic and serological data from a total of 26 patients from 18 pedigrees, all with biallelic ACP5 mutations. We observed a variability in skeletal, neurological and immune phenotypes, which was sometimes marked even between affected siblings. In total, 22 of 26 patients manifested autoimmune disease, most frequently autoimmune thrombocytopenia and systemic lupus erythematosus. Four patients were considered to demonstrate no clinical autoimmune disease, although two were positive for autoantibodies. In the majority of patients tested we detected upregulated expression of interferon-stimulated genes (ISGs), in keeping with the autoimmune phenotype and the likely immune-regulatory function of the deficient protein tartrate resistant acid phosphatase (TRAP). Two mutation positive patients did not demonstrate an upregulation of ISGs, including one patient with significant autoimmune disease controlled by immunosuppressive therapy. Our data expand the known phenotype of SPENCD. We propose that the OMIM differentiation between spondyloenchondrodysplasia and spondyloenchondrodysplasia with immune dysregulation is no longer appropriate, since the molecular evidence that we provide suggests that these phenotypes represent a continuum of the same disorder. In addition, the absence of an interferon signature following immunomodulatory treatments in a patient with significant autoimmune disease may indicate a therapeutic response important for the immune manifestations of spondyloenchondrodysplasia. Academy of Medical Sciences (AMS) [AMS-SGCL11-Briggs]

Background : Cerebral folate transporter deficiency caused by FOLR-1 mutations has been described in 2009. This condition is characterized by a 5MTHF level

Hepatic involvement is frequent in patients with cystic fibrosis (CF), with focal biliary cirrhosis being the pathognomonic hepatic manifestation. In around one-quarter of CF patients, it results in CF-associated liver disease (CFLD). This occurs as a relatively early complication with the majority of patients presenting in childhood or their early teens. However, a normal US does not preclude significant liver fibrosis and liver biopsy is an invasive procedure that is hampered by potential sampling errors. Transient elastography (TE) (Fibroscan) is a non-invasive, user-friendly and quick technique that provides an objective and reproducible measure of liver stiffness. This is accomplished with a device using an US probe mounted in the axis of a vibrator. Vibrations are transmitted by the transducer, inducing an electronic shear wave that propagates through the underlying tissue.We aimed to prospectively compare TE and transabdominal US scanning in children and adults attending a CF clinic.A total of 134 consecutive patients with documented CF were prospectively studied. In each case, transient elastography measurement was performed immediately after the routine annual US evaluation of the liver. Sonographic appearance of the liver was classified from 1 to 5. Ten validated TE measurements were performed in each patient with the result expressed in kilopascals (kPa). The median value was considered representative of the elastic modulus of the liver.Measurements were performed in 59 CF adults, 75 CF children and 31 control children. There was no relationship between age and liver stiffness in either the control group or CF patients. Elasticity values of controls, CF pancreatic sufficient (PS) patients and pancreatic insufficient (PI) CF patients with a US score3 were comparable and significantly lower than in CF patients with a US scoreor = 3 (all PI) (P0.002). Median elasticity in CF patients was significantly higher in males (4.7 kPa) than in females (3.9 kPa) (P = 0.0013).Considering the limitations of US and the low risk-benefit rate of liver biopsy in most CF patients, this preliminary study suggests that TE is an attractive non-invasive way to assess and follow-up liver disease in these patients.

Infantile myofibromatosis is a rare disorder characterized by the formation of tumors in the skin, soft tissues, bone, and viscera. We report the case of a 3-week-old girl who presented with severe hypertension due to generalized infantile myofibromatosis including renal involvement. The infant was treated by chemotherapy and showed progressive regression of the tumors. However, her evolution was marked by the development of aneurismal dilations of the renal and iliac arteries as observed in fibromuscular dysplasia. We discuss the possibility of a link between these two mesenchymal disorders.

Context: Obesity in childhood is associated with an increased mortality due to cardiovascular (CV) diseases in adulthood, independent of adult weight. Recent studies in children indicate that the atherosclerosis process starts at an early age and is linked to obesity. Objective: The aim of the study was to investigate determinants of increased carotid intima-media thickness (IMT), an early marker of atherosclerosis, in obese children. Design: A total of 104 obese children [age, 12.7 ± 0.2 yr; body mass index (BMI)-z-score, 2.8 ± 0.7] underwent an oral glucose tolerance test. Fasting levels of glucose, insulin, C-reactive protein and adhesion molecules (sICAM, sVCAM, sE-selectin), lipid profile, adiponectin, and resistin were determined. IMT was measured by ultrasound. Insulin resistance was estimated by the homeostatic model assessment index. Baseline measurements of blood parameters were obtained from 93 nonobese children (age, 13.0 ± 0.2 yr; BMI-z-score, −0.2 ± 0.9), and IMT was measured in 23 other control children with similar characteristics. Results: Univariate analysis showed a significant positive correlation between IMT and relative BMI, the degree of systolic hypertension, fasting insulin levels, homeostatic model assessment-R index, and resistin concentrations, whereas an inverse correlation with adiponectin levels was found. No correlation was obtained between IMT and classical CV risk factors such as positive familial history of type 2 diabetes or precocious CV disease, visceral obesity, or the lipid profile. C-reactive protein and adhesion molecule levels were not associated with IMT in our obese population. When controlled for sex, Tanner stage, and relative BMI, only adiponectin levels remained an independent determinant of IMT. Conclusion: Adiponectin more than conventional CV risk factors and inflammation status may be related to early atherosclerosis in obese children.

Post-transplant children are regularly followed by colour Doppler US exam. Liver parenchyma, biliary tract and portal, subhepatic and arterial vascularisation are checked. We observed a post-transplant child with spontaneous meso-portal bypass after portal vein thrombosis (PVT). After orthotopic liver transplantation (OLT), PVT is frequently observed. When it occurs early (before 3 weeks), it has been identified as a cause of graft failure. On the other hand, late PVT (after 3 weeks) can be extremely well-tolerated, with cavernous transformation of the portal vein and formation of hepatopetal collaterals that deliver blood to the liver. However, extrahepatic portal hypertension (EHPH) and its related complications can develop. Cavernoma transformation is usually seen, but spontaneous shunt is not yet described in transplant patients. Distinction from the classic cavernoma can be achieved by the depiction of a single transcapsular vessel. This bypass partially corrects the EHPH. However it was decided to completely prevent shunt development by performing a surgical mesenterico-left portal vein bypass.

During the period from 1972 to 1992, 59 children received surgical treatment at the University of Louvain Medical School for biopsy-proven Hirschsprung's disease (HD). The extent of aganglionosis was as follows: short segment restricted to the rectosigmoid or descending colon (n = 44, 75%); long segment (n = 9,15%); ultra-short segment (n = 3, 5%); unknown length because of death without autopsy (n = 3, 5%). The median age at operation was 7 months for short-segment disease compared with 14 months for those with long-segment disease. Surgical procedures used for short-segment disease were Swenson with colostomy (n = 16), Swenson-Pellerin without colostomy (n = 27), Duhamel (n = 1), and for long-segment disease were Martin (n = 3), Swenson-Deloyers (n = 2), Swenson-Boley (n = 2) and ileostomy only in = 2). Lynn's sphincteromyotomy was performed in the three ultra-short cases. There were six deaths (10%) at a median age of 86 days (range, 28 to 1545 days), three had long-segment disease, and the others were not classified because of death before curative surgery. Enterocolitis (EC) was the most common cause of death (five cases) and was also the major source of morbidity after curative surgery (12 of 44, 27%) in short-segment patients, three of seven (43%) in long-segment patients. The functional success of the procedure was evaluated in 70% of the surviving patients (37 of 53; mean follow-up, 8.7 years; range, 1.2 to 21.5), using a novel semiquantitative scoring system, specifically designed for children who have HD. This system assesses normal stool evacuation, abdominal distention, soiling, and severe incontinence. The results were compared with those from a population of 39 healthy children and adolescents and demonstrated progressive improvement in function during childhood and adolescence (P = .04) for patients treated for short-segment disease. However, function was found to be consistently poorer in all age groups when compared with healthy controls (5 to 10 years, P.01; 10 to 15 years, P.05;15 years, P.01).

Biliary complications (BCs) still remain the Achilles heel of liver transplantation (LT) with an overall incidence of 10% to 35% in pediatric series. We hypothesized that (1) the use of alternative techniques (reduced size, split, and living donor grafts) in pediatric LT may contribute to an increased incidence of BCs, and (2) surgery as a first treatment option for anastomotic BCs could allow a definitive cure for the majority of these patients. Four hundred twenty-nine primary pediatric LT procedures, including 88, 91, 47, and 203 whole, reduced size, split, and living donor grafts, respectively, that were performed between July 1993 and November 2010 were retrospectively reviewed. Demographic and surgical variables were analyzed, and their respective impact on BCs was studied with univariate and multivariate analyses. The modalities of BC management were also reviewed. The 1- and 5-year patient survival rates were 94% and 90%, 89% and 85%, 94% and 89%, and 98% and 94% for whole, reduced size, split, and living donor liver grafts, respectively. The overall incidence of BCs was 23% (n = 98). Sixty were anastomotic complications [47 strictures (78%) and 13 fistulas (22%)]. The graft type was not found to be an independent risk factor for the development of BCs. According to a multivariate analysis, only hepatic artery thrombosis and acute rejection increased the risk of anastomotic BCs (P0.001 and P = 0.003, respectively). Anastomotic BCs were managed primarily with surgical repair in 59 of 60 cases with a primary patency rate of 80% (n = 47). These results suggest that (1) most of the BCs were anastomotic complications not influenced by the type of graft, and (2) the surgical management of anastomotic BCs may constitute the first and best therapeutic option.

Congenital limb anomalies occur in Europe with a prevalence of 3.81/1,000 births and can have a major impact on patients and their families. The present study concerned a female fetus aborted at 23 weeks of gestation because she was affected by non-syndromic bilateral absence of the zeugopod (leg) and autopod (foot). Autopsy of the aborted fetus, X-ray imaging, MRI, and histochemical analysis showed that the distal extremity of both femurs was continued by a cartilage-like mass, without joint cavitation. Karyotype was normal. Moreover, no damaging variant was detected by exome sequencing. The limb characteristics of the fetus, which to our knowledge have not yet been reported in humans, suggest a developmental arrest similar to anomalies described in chicks following surgical experiments on the apical ectodermal ridge of the lower limbs.

Intramural duodenal hematomas have most frequently been reported in children in a traumatic setting. We present two cases of duodenal hematoma that occurred after upper gastrointestinal tract endoscopy with biopsy in children without significant prior medical history. The diagnosis was made by ultrasound, in correlation with the clinical presentation. Because the patients were hemodynamically stable, they were treated conservatively and the regression of the hematoma was followed up with ultrasound until its complete resolution. These cases demonstrate the risks of endoscopy, which are not to be neglected even in children without impaired coagulation, and the manner in which ultrasound can provide the correct diagnosis and follow-up.

We describe the case of a 13-month-old girl transplanted for biliary atresia with PV hypoplasia. She received the left liver lobe of her mother and presented intraoperative portal thrombosis. Because of technical reasons, the opportunity to have conventional PV reconstruction using the donor left PV stump was lost. Immediate conversion to a meso-Rex shunt, using the recipient jugular vein as a bridge between the superior mesenteric vein and the graft Rex recessus, allowed excellent portal revascularization of the transplant. We suggest that synchronous meso-Rex shunt may constitute a valid alternative to truncal PV anastomosis during pediatric LT.

A 15-year-old female had been followed in our department of pediatric radiology since the age of 11, in order to control a solitary osteochondroma (exostosis) of the right distal femur.

We report the case of a young girl who had hemihypertrophy and developed Wilms' tumor in both kidneys and clear-cell adenocarcinoma of the uterine cervix with no maternal history of stilbestrol ingestion during pregnancy. Karyotype on the second Wilms' tumor showed monosomy 22. The link between hemihypertrophy and Wilms' tumor is well known, but their association with clear-cell carcinoma of the cervix has not been previously described. (C) 1993 Wiley-Liss, Inc.

Primary angiitis of the central nervous system (PACNS) is an idiopathic, usually recurrent vasculitis confined to the brain. PACNS has been reported rarely in children, although the disease is probably underdiagnosed.: We report the clinical history of a 3-year-old girl who presented subacute neurological deterioration characterised by headache, speech regression, and altered level of consciousness. Brain MRI revealed severe inflammatory lesions involving both grey and white matters. All blood and cerebrospinal fluid (CSF) tests for inflammatory or infectious processes were negative. Over the next 10 years, the patient relapsed eight times. Brain biopsy confirmed lesions suggestive of cerebral vasculitis. Based on histopathological features and due to the absence of systemic vasculitis, the patient was considered to have PACNS. She developed partial epilepsy, and clinical stabilisation was finally achieved via continuous oral corticosteroids and immunosuppressive agents.PACNS may be the cause of subacute and relapsing inflammatory encephalopathy in children after excluding other diagnoses, such as multiple sclerosis, sarcoidosis, recurrent acute disseminated encephalomyelitis (ADEM), and primary central nervous system lymphoma. Brain biopsy is necessary to confirm the diagnosis of PACNS and exclude diseases with similar symptoms. Neurological outcome remains poor.

Objective: To evaluate if elevated D-dimer level is specific for venous malformations (VMs) and thus useful for differential diagnosis, which can be problematic even in specialized interdisciplinary centers. Localized intravascular coagulopathy, characterized by elevated D-dimer levels, has been observed in approximately 40% of patients with VMs. Design: Prospective convenience sample accrued from 2 interdisciplinary sites. Setting: Two interdisciplinary centers for vascular anomalies in Brussels, Belgium, and Caen, France Participants: The study population comprised 280 patients with clinical data, Doppler ultrasonograms (for 251 patients), and coagulation parameter measurements. Main Outcome Measure: Measurement of D-dimer levels. Results: A VM was diagnosed in 195 of 280 patients (69.6%), and 83 of them had elevated D-dimer levels; the sensitivity of D-dimer dosage was 42.6% (95% confidence interval, 35.6%-49.5%). Among the 85 patients without VM, D-dimer levels were elevated only in 3 patients; the specificity of the dosage was 96.5% (95% confidence interval, 92.5%-100%). Conclusions: Elevated D-dimer level is highly specific for VMs (pure, combined, or syndromic), and therefore this easy and inexpensive biomarker test should become part of the clinical evaluation of vascular anomalies. It can detect hidden VMs and help differentiate glomuvenous malformation (normal D-dimer levels) from other multifocal venous lesions. Elevated D-dimer level also differentiates a VM from a lymphatic malformation. Moreover, slow-flow Klippel-Trenaunay syndrome (capillaro-lymphatico-venous malformation with limb hypertrophy) can be distinguished from fast-flow Parkes Weber syndrome (capillary malformation with underlying multiple microfistulas and limb hypertrophy). For these reasons, D-dimer level measurement is a useful complementary tool for diagnosing vascular anomalies in everyday practice.

We describe a neurologically symptom-free adolescent with aggressive vertebral body haemangiomas at two sites.

OBJECTIVE. We sought to investigate whether the outer diameter of the vermiform appendix on cross-sectional sonography is as reliable a criterion with which to confirm acute appendicitis in patients with cystic fibrosis as in those without cystic fibrosis. CONCLUSION. The outer appendiceal diameter of 6 mm or more cannot be considered a reliable criterion for the diagnosis of acute appendicitis in patients with cystic fibrosis.

Recent advances in diffusion tensor imaging (DTI) have made it possible to reveal white matter anatomy and to detect neurological abnormalities in children. However, the clinical use of this technique is hampered by the lack of a normal standard of reference. The goal of this study was to initiate the establishment of a database of DTI images in children, which can be used as a normal standard of reference for diagnosis of pediatric neurological abnormalities. Seven pediatric volunteers and 23 pediatric patients (age range: 0-54 months) referred for clinical MR examinations, but whose brains were shown to be normal, underwent anatomical and DTI acquisitions on a 1.5 T MR scanner. The white matter maturation, as observed on DTI color maps, was described and illustrated. Changes in diffusion fractional anisotropy (FA), average apparent diffusion constant (ADC(ave)), and T2-weighted (T2W) signal intensity were quantified in 12 locations to characterize the anatomical variability of the maturation process. Almost all prominent white matter tracts could be identified from birth, although their anisotropy was often low. The evolution of FA, shape, and size of the white matter tracts comprised generally three phases: rapid changes during the first 12 months; slow modifications during the second year; and relative stability after 24 months. The time courses of FA, ADC(ave), and T2W signal intensity confirmed our visual observations that maturation of the white matter and the normality of its architecture can be assessed with DTI in young children. The database is available online and is expected to foster the use of this promising technique in the diagnosis of pediatric pathologies.

We present a case of spinal cord injury due to birth trauma and assess the value of sonography for diagnosis, lesion characterization, and follow-up. Sonography is a non-invasive and easily reproducible imaging method for examining a ventilated child, and its initial sensitivity is comparable to that of MRI. Sonography is the method of choice for guiding diagnosis in this type of traumatic lesion to the newborn.

In most cases of total hepatectomy (TH) required for hepatoblastoma (HB), the retrohepatic inferior vena cava (IVC) has to be removed with the native liver for complete tumor excision. Because the liver graft procured by living donation has no IVC, a reconstruction of the recipient IVC is needed. We report our experience with living-related liver transplantation (LRLT) and IVC replacement in such cases.Between May 1998 and December 1999, four children underwent TH, including IVC and LRLT with IVC replacement for otherwise irresectable HB after chemotherapy (SIOPEL 2 and 3 protocols). IVC reconstruction used an allogenic iliac vein procured from a cadaveric donor (bank graft) in two cases and an internal jugular vein procured from the donor parent in two cases. Median age and weight at surgery were 17 months (range 10-60) and 9.6 kg (range 8.3-17.9).In the living donors, there were two complications of the procurement: one intra-abdominal biliary collection and one subcutaneous abscess. In all four children, complete excision of the tumor could be achieved without any intra-operative complication. One patient died 5 months after LRLT due to lung metastases. Three patients were alive and well with no evidence of tumor recurrence 13-24 months after surgery. Reconstructed IVC was patent in two patients, and asymptomatic thrombosis occurred 2 years after operation in one patient.Total hepatectomy including the retrohepatic IVC is not a technical obstacle to LRLT. Therefore, scheduled surgery, at the best time after chemotherapy, can be considered in all patients with otherwise irresectable HBs.

BACKGROUND: Lymphatic malformations (LM) are rare benign congenital tumors appearing mainly in the head and neck with a considerably variable outcome. A need exists to validate a staging system, taking into account the prognosis of the malformation, including preoperative and postoperative complications, long-term sequelae, and persistence of the disease to improve parental counseling and evaluate the outcome of a surgical treatment of such tumors. METHODS: Twenty-two patients treated for LM were selected from a series of 129 patients operated on for congenital malformations of the head and neck between 1986 and 1997 at St-Luc University Hospital, Brussels, Belgium. Their charts were reviewed retrospectively, with a special focus on the anatomic location of the lesions and all the complications reported. According to de Serres et al, LM up to now have been divided into six possible categories according to their unilateral or bilateral infrahyoid and/or suprahyoid locations. RESULTS: Stage I (unilateral infrahyoid): nine patients, 11% of complications (without mediastinal extension: 0%, with mediastinal extension: 50%); stage II (unilateral suprahyoid): three patients, 33% of complications; stage III (unilateral suprahyoid and infrahyoid): eight patients, 75% of complications; stage V (bilateral suprahyoid and infrahyoid): two patients, 100% of complications. None of the children was initially seen with stage IV (bilateral suprahyoid) or stage VI (bilateral infrahyoid) LM. Overall complications, preoperative complications, postoperative com- plications, and long-term morbidity showed a significant in- crease from stage I to V (p

Article abstract The authors describe the clinical, radiologic, and pathologic features of a neonatal spinal neurenteric cyst (NC) presenting with long-lasting fever and acute myelopathy, and compare this observation with other infants reported in the literature. This observation shows that NC must be considered in the differential diagnosis of acute myelopathy with persistent fever in infancy. Fever is attributed to degenerative changes in the NC, triggering inflammatory cell infiltration and tumor necrosis factor alpha secretion.

Out of our series of 24 children seropositive for the Human Immunodeficiency Virus (HIV), parotid gland enlargement was noted in 4 children with AIDS-related complex (ARC) presenting also a Lymphocytic Interstitial Pneumonitis (LIP) on their chest radiographs. The ultrasound (US) aspect of the parotid gland suggests acinar enlargement (suggesting the presence of lymphocytic infiltration). The aspect displayed in the parotid mirrors the process developing in other areas (lungs, liver, spleen, lymph-nodes), i.e. a syndrome of lymphocytic (CD8) proliferation present at the stage of ARC.

Between 1986 and 1995, 128 patients were treated for various head and neck congenital malformations at Saint-Luc University Hospital, Louvain. We report three cases of fourth branchial pouch cysts requiring surgical removal. One of these cases presented with a third branchial pouch remnant on the same side and subsequently a fourth branchial pouch sinus. To our knowledge, this is the first case published in the literature. A fourth branchial pouch sinus tract can become manifest clinically by recurrent episodes of neck abscess or acute suppurative thyroiditis (especially in infants). The tract can be identified with a barium swallow during the period of latency and hypopharyngeal endoscopy under general anesthesia. Total excision of the fistula with dissection up to the pyriform sinus with or without a left thyroid gland lobectomy and isthmectomy is the treatment of choice.

BACKGROUND: The lack of a consensus in the literature on the imaging strategy in Langerhans cell histiocytosis (LCH) bone lesions in childhood. OBJECTIVE: To evaluate the relative value of radionuclide bone scan (RBS) and radiographic skeletal survey (RSS) in the detection of LCH bone lesions, both in the initial work-up of the disease and during the follow-up period. MATERIALS AND METHODS: Ten children with bone lesions evaluated by means of RSS and RBS in a retrospective study (1984-1993). RESULTS: Fifty radiologically and/or scintigraphically abnormal foci were detected: 27 anomalies in the initial work-up (12 by both RSS and RBS, 8 by RSS only and 7 by RBS only) and 23 additional anomalies during follow-up (10 by both RSS and RBS, 10 by RSS only and 3 by RBS only). RSS+/RBS- lesions (n = 18) are more frequently encountered in the skull (P = 0.038), and more frequently lack radiologic signs of osteoblastic activity (P = 0.020), than RSS+/RBS+ lesions (n = 22). RSS-/ RBS+ abnormalities (n = 10) were most frequently insignificant. CONCLUSION: In the initial work-up both RSS and RBS should be carried out, while in the follow-up only RSS should be performed.

OBJECTIVE: To evaluate the strategy of a combined diagnostic and therapeutic approach in children with intra-abdominal organ injury following blunt abdominal trauma. DESIGN: Retrospective clinical study. SETTING: Pediatric intensive care unit of an university hospital. PATIENTS: 38 children with documented intra-abdominal injury. INTERVENTION: Initial non-surgical treatment by a team of pediatric intensivists, radiologists and surgeons. MEASUREMENTS AND RESULTS: Physical examination, oriented blood and urine tests, plain abdominal film, abdominal ultrasound (US) and computed tomography (CT) with contrast. US documented intra-abdominal fluid in 30 and initial organ lesion in 14 out of 31 patients evaluated. Abdominal CT demonstrated the precise organ lesion in 34 out of 36 patients examined with solid organ lesion. Early laparotomy was needed in 7 because of severe shock, pneumoperitoneum and ruptured diaphragm, and delayed surgery in 6 patients. All 38 patients regained a normal life. CONCLUSIONS: The stepped diagnostic approach combined with initial non-surgical treatment by a team provided accurate diagnosis and appropriate treatment. Abdominal US, by demonstrating free intra-abdominal fluid is very sensitive to detect patients with intra-abdominal organ injury, CT scan with contrast is needed to give precise information of specific organ lesions.

Two years after an orthotopic liver transplantation, a multifocal hepatic tumor with lymphonodular metastases, identified as a fibrosarcoma, developed in a 4-year-old girl being treated with cyclosporine. On a needle biopsy sample, genetic typing of the HLA-DR group revealed that tumoral cells were from the recipient.

Biliary atresia is the most common indication for orthotopic liver transplantation (OLT) in children. The polysplenia syndrome anomalies, which occur in approximately 10% of children with biliary atresia, may represent special difficulties at liver transplantation. We have reviewed our experience with this syndrome in 116 children with biliary atresia who underwent liver transplantation between March 1984 and December 1989. The main features of the polysplenia syndrome, which included absence of the inferior vena cava, preduodenal portal vein, midgut malrotation, aberrant hepatic artery, and situs inversus, were encountered in 12 of the 116 children (10.3%). Severe portal vein hypoplasia (3.5 mm or smaller) was also present in 7 of these children. Eight patients received a complete and four received a reduced liver graft. The vascular anomalies increased the technical difficulty of OLT but could be surmounted, although they did contribute to the peroperative death of one child. The 1-month survival rate was 83% for the 12 children with features of the polysplenia syndrome and 88% for the other 92 children with biliary atresia alone.

A 4-year-old boy and a 14-year-old girl referred for a cholestatic syndrome were found to have a unifocal stricture of the extrahepatic bile duct. Both radiological (endoscopic-retrograde-choledocopancreatography) and histological findings were suggestive of primary sclerosing cholangitis. There was no past history of chronic inflammatory bowel disease nor any other disorder. Serum autoimmune markers were negative. Complete remission was observed after surgical drainage, and both patients remained symptom-free after a follow-up of 12 months and 8 years, respectively. Such unifocal form of the disease may have a better prognosis than the plurifocal disease. The absence of associated disorders and autoimmunity may also be an indicator of better prognosis in these patients.