Gaslini Children Hospital

Genova, Italy

Gaslini Children Hospital

Genova, Italy
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Baban A.,Bambino Gesu Children Hospital | Marini M.,Gaslini Children Hospital | Trocchio G.,Gaslini Children Hospital | Santilli A.,Bambino Gesu Children Hospital | And 9 more authors.
American Journal of Medical Genetics, Part A | Year: 2014

Tetralogy of Fallot (TOF) (OMIM #187500) is the most frequent conotruncal congenital heart defect (CHD) with a range of intra- and extracardiac phenotypes. TBX5 is a transcription factor with well-defined roles in heart and forelimb development, and mutations in TBX5 are associated with Holt-Oram syndrome (HOS) (OMIM#142900). Here we report on the screening of 94 TOF patients for mutations in TBX5, NKX2.5 and GATA4 genes. We identified two heterozygous mutations in TBX5. One mutation was detected in a Moroccan patient with TOF, a large ostium secundum atrial septal defect and complete atrioventricular block, and features of HOS including bilateral triphalangeal thumbs and fifth finger clinodactyly. This patient carried a previously described de novo, stop codon mutation (p.R279X) located in exon 8 causing a premature truncated protein. In a second patient from Italy with TOF, ostium secundum atrial septal defect and progressive arrhythmic changes on ECG, we identified a maternally inherited novel mutation in exon 9, which caused a substitution of a serine with a leucine at amino acid position 372 (p.S372L, c.1115C>T). The mother's clinical evaluation demonstrated frequent ventricular extrasystoles and an atrial septal aneurysm. Physical examination and radiographs of the hands showed no apparent skeletal defects in either child or mother. Molecular evaluation of the p.S372L mutation demonstrated a gain-of-function phenotype. We also review the literature on the co-occurrence of TOF and HOS, highlighting its relevance. This is the first systematic screening for TBX5 mutations in TOF patients which detected mutations in two of 94 (2.1%) patients. © 2014 Wiley Periodicals, Inc.


Ghiggeri G.M.,Gaslini Children Hospital | Gigante M.,University of Foggia | Di Donato A.,Gaslini Children Hospital | Di Donato A.,Instituto G Gaslini
International Journal of Nephrology | Year: 2013

The kidney glomerular podocytes are the cellular target of many chronic nephropathies both determined and acquired genetically. Mutations that affected the expression and/or the function of nephrin, a key component of the slit-diaphragm, are often causes of these pathologies. Recent findings showed that murine podocytes could undergo epithelial-mesenchymal transformation (EMT), suggesting new hypotheses about the pathogenesis of glomerular fibrosis. Here, we show that also human podocytes can undergo EMT, but more importantly nephrin ablation itself can trigger this phenotypic transformation. In fact, a model of human podocyte with engineered nephrin deficiency constitutionally expressed high levels of α -SMA, vimentin, fibronectin, and other hallmarks of EMT. Since it is known that cell contact abrogation is one of the triggers of EMT, we reasoned that nephrin loss could account for such cell junction disruption and cause the EMT. Therefore, we demonstrated that also normal podocytes could spontaneously undergo EMT if grown in Ca2+-free medium, which is known to impair cell contacts. The analysis of the main intracellular signal transduction pathways evidenced some major anomalies consequent with the nephrin abrogation. The most intriguing was the activation of β -catenin pathway, which plays a critical role in podocyte ontogenesis as well as in the nephrin expression and EMT regulation. Also other important signaling proteins, like NF- B, p53, and retinoblastoma protein (RB), showed important activity modifications. Interestingly, most of the above indicated signaling pathway alterations were again reproducible by cell junction rupture, induced by Ca 2+ deprivation. Finally, immunofluorescence analysis on kidney sections of patients with NS of Finnish type confirmed the constitutive expression of α -SMA. © 2013 Gian Marco Ghiggeri et al.


PubMed | Markusovszky Hospital, San Gerardo Hospital, French Institute of Health and Medical Research, Semmelweis University and 13 more.
Type: Journal Article | Journal: PloS one | Year: 2016

Childhood cancer survivors are at high risk of long-term adverse effects of cancer and its treatment, including cardiac events. The pan-European PanCareSurFup study determined the incidence and risk factors for cardiac events among childhood cancer survivors. The aim of this article is to describe the methodology of the cardiac cohort and nested case-control study within PanCareSurFup.Eight data providers in Europe participating in PanCareSurFup identified and validated symptomatic cardiac events in their cohorts of childhood cancer survivors. Data on symptomatic heart failure, ischemia, pericarditis, valvular disease and arrhythmia were collected and graded according to the Criteria for Adverse Events. Detailed treatment data, data on potential confounders, lifestyle related risk factors and general health problems were collected.The PanCareSurFup cardiac cohort consisted of 59,915 5-year childhood cancer survivors with malignancies diagnosed between 1940 and 2009 and classified according to the International Classification of Childhood Cancer 3. Different strategies were used to identify cardiac events such as record linkage to population/ hospital or regional based databases, and patient- and general practitioner-based questionnaires.The cardiac study of the European collaborative research project PanCareSurFup will provide the largest cohort of 5-year childhood cancer survivors with systematically ascertained and validated data on symptomatic cardiac events. The result of this study can provide information to minimize the burden of cardiac events in childhood cancer survivors by tailoring the follow-up of childhood cancer survivors at high risk of cardiac adverse events, transferring this knowledge into evidence-based clinical practice guidelines and providing a platform for future research studies in childhood cancer patients..


Martinoli C.,University of Genoa | Garello I.,University of Genoa | Marchetti A.,University of Genoa | Palmieri F.,University of Genoa | And 3 more authors.
European Journal of Radiology | Year: 2012

In newborns, US has an established role in the detection and management of developmental dysplasia of the hip. Later in childhood, when the limping child is a major diagnostic dilemma, US is extremely helpful in the identification of the varied disease processes underlying this condition, as transient synovitis, septic arthritis, Perthes disease and slipped femoral capital epiphysis. In adolescent practicing sporting activities, US is an excellent means to identify apophyseal injures about the pelvic ring, especially when avulsions are undisplaced and difficult-to-see radiographically. Later on, in the adulthood, US is an effective modality to diagnose tendon and muscle injuries about the hip and pelvis, identify effusion or synovitis within the hip joint or its adjacent bursae and guide the treatment of these findings. The aim of this article is to provide a comprehensive review of the most common pathologic conditions about the hip, in which the contribution of US is relevant for the diagnostic work-up. © 2011 Elsevier Ireland Ltd. All rights reserved.


Girtler N.,University of Genoa | Girtler N.,Gaslini Children Hospital | Casari E.F.,University of Genoa | Casari E.F.,Gaslini Children Hospital | And 7 more authors.
Clinical and Experimental Rheumatology | Year: 2010

Objectives: Studying the characteristics of resilience may help to explain how, in the face of a chronic disease, people are able to cope in productive and effective ways. The Wagnild and Young Resilience Scale (RS) is an appropriate instrument to study resilience and has already been translated from the original English version into several languages. The aim of this study was to validate the Italian version of the RS, a 25-item scale ranging from 25 to 175 where higher scores indicate stronger resilience. Methods: The Minimal Translation Criteria were followed to translate the scale which was then filled out by 1090 students to assess the reliability, stability, internal consistency and concurrent validity. Results: Time stability was assessed in a sample of 117 students (M age = 20.18 yr, SD 1.25) by test-retest correlation (r=0.78). RS reliability was evaluated in a second sample of 973 students (M age = 16.95 yr, SD 1.50) with RS mean of 126.6 (SD 17.4). Concurrent validity was assessed by correlation with General Health Questionnaire (r=-0.51), Ego-Resilience Scale (r=0.63) and Beck Depression Inventory (r=-0.45). Internal consistency was evaluated by Cronbach alpha (α=0.84). Principal component analysis was performed on 24 out of the 25 items and resulted in six components. Conclusion: Our data indicated that the 24-item Italian version of the RS scale can be considered a useful instrument to measure resilience and can be used by healthcare staff to help patients cope effectively with stressful situations such as rheumatic and other chronic diseases. © Copyright CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 2010.


Gallucci M.,University of L'Aquila | Smith J.D.,Drexel University | Limbucci N.,Careggi Hospital | Rossi A.,Gaslini Children Hospital | And 4 more authors.
Neuroradiology Journal | Year: 2012

Some rare neurological diseases affecting children have no well defined etiology and pathogenetic mechanisms. In this article diseases like Reye syndrome, Behcet disease, pediatric neurosarcoidosis, Posterior Reversible Encephalopathy Syndrome are described. Some of the main neuroradiological differential aspects are also critically considered. Reye syndrome is characterized by symmetric thalamic, white matter and basal ganglia lesions, in children with recent history of salycilates or immunosuppressive drugs intake. The most typical MRI feature of neurosarcoidosis is basilar meningeal thickening and enhancement with intraparenchymal enhancing nodules and white matter focal abnormalities. The classical distribution of lesions helps differential diagnosis with infectious meningoencephalitis. Differential diagnosis with relapsing-remitting multiple sclerosis his helped by the evidence of meningeal abnormalities. Neuro-Behçet is characterized by mesodiencephalic lesions in children with encephalopathy and coexistence of oral and genital ulcers and ocular abnormalities. PRES can be differentiated from vasculitis for the typical posterior white matter involvement and the different clinical features.


Torre M.,Gaslini Children Hospital | Baban A.,Gaslini Children Hospital | Buluggiu A.,Gaslini Children Hospital | Costanzo S.,Gaslini Children Hospital | And 7 more authors.
Journal of Thoracic and Cardiovascular Surgery | Year: 2010

Objective: Poland syndrome is a rare congenital anomaly characterized by complete or partial agenesis of the pectoralis major muscle variably associated with other thoracic malformations, upper limb malformations, or both. More than 20 patients with dextrocardia and left-sided Poland syndrome have been previously described. The association between these 2 rare anomalies suggests a causal relationship, but the etiopathogenetic mechanism has not been clarified yet. We studied the clinical correlation between these 2 anomalies, and we tried to elucidate whether dextrocardia or Poland syndrome comes first. Methods: This is a multicentric multidisciplinary study conducted over the last 5 years. We identified 122 patients with Poland syndrome, and we investigated heart position through different imaging techniques. Logistic regression statistical analyses were carried out. Results: We observed dextrocardia in 14 (11.5%) patients, which was never associated with situs inversus. All of them presented with left-sided Poland syndrome and partial agenesis of 2 or more ribs. Conversely, all patients with Poland syndrome with partial agenesis of 2 or more ribs presented with dextrocardia, whereas dextrocardia was never associated with partial agenesis of a single rib. Three patients with dextrocardia presented with simple congenital heart defects. Conclusions: These findings suggest that mechanical factors during embryonic life could explain the strong association between left-sided Poland syndrome and dextrocardia. According to this hypothesis, partial agenesis of 2 or more ribs is needed to displace the heart toward the right side. The peculiar features of dextrocardia when associated with Poland syndrome (neither associated with situs inversus nor complex intracardiac anomalies) support our hypothesis. © 2010 The American Association for Thoracic Surgery.


Gallucci M.,University of L'Aquila | Smith J.D.,Drexel University | Limbucci N.,Careggi Hospital | Giangaspero F.,University of Rome La Sapienza | Rossi A.,Gaslini Children Hospital
Neuroradiology Journal | Year: 2012

Acute post-infectious immune disorders include Acute Disseminated Encephalomyelitis (ADEM) and its variants such as Acute Hemorrhagic Encephalomyelitis (AHEM), acute necrotizing hemorrhagic leukoencephalitis (ANHLE) of Weston Hurst, multiphasic and recurrent ADEM. Acute Necrotizing Encephalopathy of Childhood (ANE or ANEC) represents a dramatic event, consequent to viral infections, especially Influenza-A, and is now considered different from ADEM. ADEM and variants are classically described as uniphasic syndrome occurring in association with an immunization or vaccination (postvaccine encephalomyelitis) or systemic viral infection (parainfectious encephalomyelitis). However, multiphasic forms are not rare. Pathologically, there is perivascular inflammation, edema, and demyelination within the CNS. Clinical features are focal or multifocal neurologic disorder following exposure to virus or receipt of vaccine. The onset of the CNS disorder is usually rapid and include encephalopathy ranging from lethargy to coma, seizures, and focal and multifocal signs reflecting cerebral and spinal cord involvement. The mortality rate is estimated at 10 to 30 percent, with complete recovery rates of 50 percent cited. Poor prognosis is correlated with severity and abruptness of onset of the clinical syndrome. Multifocal CNS lesions are generally evident on MRI that can be similar from those observed in MS.


The kidney glomerular podocytes are the cellular target of many chronic nephropathies both determined and acquired genetically. Mutations that affected the expression and/or the function of nephrin, a key component of the slit-diaphragm, are often causes of these pathologies. Recent findings showed that murine podocytes could undergo epithelial-mesenchymal transformation (EMT), suggesting new hypotheses about the pathogenesis of glomerular fibrosis. Here, we show that also human podocytes can undergo EMT, but more importantly nephrin ablation itself can trigger this phenotypic transformation. In fact, a model of human podocyte with engineered nephrin deficiency constitutionally expressed high levels of -SMA, vimentin, fibronectin, and other hallmarks of EMT. Since it is known that cell contact abrogation is one of the triggers of EMT, we reasoned that nephrin loss could account for such cell junction disruption and cause the EMT. Therefore, we demonstrated that also normal podocytes could spontaneously undergo EMT if grown in Ca(2+)-free medium, which is known to impair cell contacts. The analysis of the main intracellular signal transduction pathways evidenced some major anomalies consequent with the nephrin abrogation. The most intriguing was the activation of -catenin pathway, which plays a critical role in podocyte ontogenesis as well as in the nephrin expression and EMT regulation. Also other important signaling proteins, like NF-B, p53, and retinoblastoma protein (RB), showed important activity modifications. Interestingly, most of the above indicated signaling pathway alterations were again reproducible by cell junction rupture, induced by Ca(2+) deprivation. Finally, immunofluorescence analysis on kidney sections of patients with NS of Finnish type confirmed the constitutive expression of -SMA.


PubMed | Gaslini Children Hospital
Type: Journal Article | Journal: The Journal of thoracic and cardiovascular surgery | Year: 2010

Poland syndrome is a rare congenital anomaly characterized by complete or partial agenesis of the pectoralis major muscle variably associated with other thoracic malformations, upper limb malformations, or both. More than 20 patients with dextrocardia and left-sided Poland syndrome have been previously described. The association between these 2 rare anomalies suggests a causal relationship, but the etiopathogenetic mechanism has not been clarified yet. We studied the clinical correlation between these 2 anomalies, and we tried to elucidate whether dextrocardia or Poland syndrome comes first.This is a multicentric multidisciplinary study conducted over the last 5 years. We identified 122 patients with Poland syndrome, and we investigated heart position through different imaging techniques. Logistic regression statistical analyses were carried out.We observed dextrocardia in 14 (11.5%) patients, which was never associated with situs inversus. All of them presented with left-sided Poland syndrome and partial agenesis of 2 or more ribs. Conversely, all patients with Poland syndrome with partial agenesis of 2 or more ribs presented with dextrocardia, whereas dextrocardia was never associated with partial agenesis of a single rib. Three patients with dextrocardia presented with simple congenital heart defects.These findings suggest that mechanical factors during embryonic life could explain the strong association between left-sided Poland syndrome and dextrocardia. According to this hypothesis, partial agenesis of 2 or more ribs is needed to displace the heart toward the right side. The peculiar features of dextrocardia when associated with Poland syndrome (neither associated with situs inversus nor complex intracardiac anomalies) support our hypothesis.

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