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Introduction: Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammation of the esophagus, characterized by symptoms related to esophageal dysfunction, resulting from severe eosinophilic infiltration of the esophageal mucosa. It is common in atopic subjects and food antigens have been identified as the most common triggers. However, a seasonal variation in EoE prevalence, correlated with air pollen levels, is reported, suggesting that also aeroallergens may play a role. Little is known about the interplay between EoE and concomitant atopy treatment for aeroallergens. Case presentation: We describe the case of an 11-year-old boy who presented dysphagia, vomiting, drooling, and chest pain while eating meat, developed 15 months after receiving sublingual immunotherapy (SLIT) for Alternaria (SUBLIVAC®). He underwent esophagogastroduodenoscopy (EGD) revealing severe eosinophilic predominant inflammation (100 eos/HPF), consistent with the diagnosis of EoE, not improving at the EGDs performed after both omeprazole and topical corticosteroids treatment, despite symptom improvement. Afterward, immunotherapy was switched from sublingual to injective form. At the EGD performed 1 month later, macroscopic examination of the esophageal mucosa was normal and eosinophilic infiltration was significantly decreased (5-10 eos/HPF). Conclusions: SLIT may induce EoE by chronic antigenic exposure of oral mucosa in patients with a robust allergic susceptibility: while attenuating the IgE-mediated immune reactions, the progressive contact with the causative allergen might induce a chronic stimulation of the immune system with the consequent activation of tissue eosinophils. Our data suggest monitoring patients receiving SLIT for EoE symptoms and to discontinue SLIT on their earlier appearance, possibly as a first-line treatment.
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In some subjects with severe neurological diseases, a reduced immune response to seasonal influenza vaccine has been demonstrated. Patients with Williams or Cornelia de Lange syndrome frequently have abnormalities in neurodevelopment. This study has evaluated the immunogenicity, safety and tolerability of a monovalent 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine in these subjects. Eighteen patients with Williams syndrome (ten males; mean age ± standard deviation [SD] 12.74 ± 4.49 years), 11 with Cornelia de Lange syndrome (six males; mean age 12.90 ± 4.85 years) and 30 age- and gender-matched healthy controls (16 males; mean age 12.49 ± 4.55 years), never vaccinated against influenza, received a dose of the vaccine between 1 and 30 November 2009. Four weeks later, the seroconversion rates in the three groups were between 72% and 80% and the seroprotection rates were 100%, with a similar increase in antibody levels. Two months later, most of the subjects remained seroconverted with no statistically significant difference between the groups, and about 94% of the patients with Williams syndrome, all of those with Cornelia de Lange syndrome and all of the healthy controls were still seroprotected. Safety and tolerability were very good, with no difference between the groups. None of the patients developed documented influenza during the study period. These results show that the immunogenicity, safety, and tolerability of a single dose of the monovalent 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine in children and adolescents with Williams or Cornelia de Lange syndrome and moderate to severe mental disabilities is very good, and similar to that of healthy subjects.
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Adjuvantes Imunológicos/administração & dosagem , Síndrome de Cornélia de Lange/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/imunologia , Pandemias , Polissorbatos/administração & dosagem , Esqualeno/administração & dosagem , Síndrome de Williams/imunologia , Adolescente , Criança , Humanos , Vacinas contra Influenza/efeitos adversosRESUMO
OBJECTIVES: Aortic valve stenosis (AVS) is the most common cause of surgical valve replacement worldwide. The vasoactive peptide urotensin II (UII) is upregulated in atherosclerosis and several other cardiovascular diseases; however, its role in the pathogenesis of AVS remains to be determined. Here, we investigated the expression of UII, urotensin-related peptide (URP), and the urotensin receptor (UT) and the role this system plays in AVS. METHODS: Immunohistochemistry and reverse-transcriptase polymerase chain reaction were used to examine the cellular localization and mRNA expression, of UII, URP, and UT in calcified and noncalcified aortic valves. Human aortic valve interstitial cells were isolated from normal valves and treated with UII or URP, and changes in cell proliferation, cholesterol efflux, calcium deposition, and ß-catenin translocation were assessed. RESULTS: The mRNA expression of UII, URP, and UT was significantly greater in patients with AVS. There was abundant presence of UII, URP, and UT immunostaining in diseased compared with nondiseased valves and correlated significantly with presence of calcification (P < .0001) and fibrosis (P < .0001). Treating human aortic valve interstitial cells with UII or URP significantly increased cell proliferation (P < .0001) and decreased cholesterol efflux (P = .0011 and P = .0002, respectively). UII also significantly reduced ABCA1 protein expression (P = .0457) and increased ß-catenin nuclear translocation (P < .0001) and mineral deposition (P < .0001). CONCLUSIONS: Together, these data suggest that the urotensin system plays a role in the pathogenesis of AVS and warrants further investigation.
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Myiasis by Oestrus ovis, the zoonotic infestation with Diptera larvae, primarily diagnosed in goats and rams in tropical and Mediterranean countries, is an uncommon disease in humans; indeed, literature data are still lacking. Nevertheless, few cases of human myiasis have been reported, leading to benign or severe complications. Here, we report a rare case of human rhinomyiasis detected in Northern Italy. A 39-year-old Italian woman, returning from vacation in Corsica, showed several sinusal symptoms and progressive asthenia and was therefore admitted at the Otorhinolaryngology Unit of Biella Hospital, Italy. Endoscopic examination of the nasal cavity revealed some formations, morphologically identified as O. ovis larvae. The patient then underwent endoscopic sinus surgery, followed by complete resolution of symptoms. Clinical presentation, diagnostic work-up and therapeutic procedures have been compared with few other cases found in the literature.
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Miíase/diagnóstico , Miíase/cirurgia , Doenças Nasais/diagnóstico , Doenças Nasais/cirurgia , Doença Relacionada a Viagens , Adulto , Astenia/parasitologia , Feminino , França , Humanos , Cirurgia Endoscópica por Orifício NaturalRESUMO
Cornelia de Lange syndrome (CdLS) is a multiple congenital anomaly/mental retardation syndrome, characterized by distinctive facial features, generalized hirsutism, growth and cognitive dysfunction, microcephaly and limb abnormalities. Currently mutations of three different genes, NIPBL, SMC1A, and SMC3, are known to be related to the CdLS phenotype with an overall detection rate of about 50%. Few data are available regarding the level of autonomy in everyday life of CdLS patients. Due to the collaboration of the Italian parents' support group, we collected information regarding clinical and behavioral problems and everyday abilities of 45 CdLS patients between 13 and 39 years, using a specific multi-item questionnaire. To better analyze clinical information we divided our patients into three groups according to age: 13-20, 21-29, and over 30 years. Data from clinical, malformative and behavioral problems were not significantly different from those described for CdLS patients. Regarding personal autonomies this study showed the significant limitations of these individuals. It is interesting to observe that patients between 21 and 29 years, showed the best performance, while those over 30 had more severe difficulties. We suggest that these data be interpreted as a minimum level of autonomy achievable for CdLS adolescent/young adults, as the level of care, rehabilitation and stimulation of these patients has increased in the last 30 years.
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Atividades Cotidianas , Síndrome de Cornélia de Lange/patologia , População Branca , Adolescente , Adulto , Distribuição por Idade , Cognição , Síndrome de Cornélia de Lange/complicações , Emprego , Humanos , Deficiência Intelectual/complicações , Itália , Conhecimento , Linguística , Pais , Instituições Acadêmicas , Comportamento Social , Adulto JovemRESUMO
Mutations in genes coding for transducers participating in the RAS/MAPK pathway have been identified as the molecular cause underlying a group of clinically related developmental disorders with cognitive deficits of variable severity. To determine the spectrum of cognitive defects associated with dysregulation of this signal cascade, we studied the profile of cognitive abilities in patients with mutations affecting the PTPN11, SOS1, HRAS, KRAS, BRAF, RAF1, and MEK1 genes and phenotype-genotype correlations. Our findings support the observation that heterogeneity in cognitive abilities can be at least partially ascribed to the individual affected genes and type of mutation involved. While mutations affecting transducers upstream of RAS were less frequently associated with mental retardation, mutations in downstream components of the pathway were generally associated with a more severe cognitive impairment. Among patients with a heterozygous PTPN11 mutation, the T468M substitution was associated with a mean IQ significantly higher compared to that of individuals carrying the N308D change. Our study provides insights on the range of cognitive abilities in patients with gene mutations causing dysregulation of RAS signaling suggesting that the presence and severity of cognitive involvement can be predicted in part by the gene involved.
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Transtornos Cognitivos/genética , Sistema de Sinalização das MAP Quinases/genética , Proteínas ras/genética , Adolescente , Adulto , Criança , Pré-Escolar , Deficiências do Desenvolvimento/genética , Feminino , Humanos , Lactente , MAP Quinase Quinase 1/genética , Masculino , Mutação , Fenótipo , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína SOS1/genética , Adulto JovemRESUMO
Congenital heart defects (CHDs) have been estimated to occur in approximately 20% of patients with Brachmann-de Lange syndrome (BDLS, also known as Cornelia de Lange syndrome, OMIM 122470). We report on the results of a prospective echocardiographic evaluation of a cohort of 87 Italian BDLS patients with longitudinal follow-up from 5 to 12 years. A cardiac anomaly was identified in 29/87 (33.3%) including 28 (32.2%) patients with a structural CHD, and an additional patient (1.2%) with isolated non-obstructive hypertrophic cardiomyopathy (HCM). Of the 28 patients with a CHD, 12 (42.9%) had an isolated obstructive CHD, 10 of which were pulmonary stenosis (36%), 8 (28.6%) had an isolated left to right shunt, and the remainder showed a combination of structural anomalies. Overall incidence of pulmonary stenosis was 39% (11/28). Isolated late-onset mitral or tricuspid valve dysplasia, albeit hemodynamically insignificant, was detected at follow-up examination in 4 (14.3%) patients older than 10 years, previously known to be normal. In contrast to previous studies, only two patients required surgery, one for closure of a large perimembranous ventricular septal defect (VSD) and associated ASD closure (1), and another for VSD closure and relief of pulmonary valve stenosis (1). The remainder are receiving medical follow-up. We believe that the overall frequency (33.3%) and evidence of 4 late onset dysplastic valves anomalies justifies both echocardiographic assessment in all BDLS patients at the first diagnostic assessment, and later on during medical follow-up.
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Síndrome de Cornélia de Lange/terapia , Cardiopatias Congênitas/terapia , Comunicação Interatrial/terapia , Doenças das Valvas Cardíacas/terapia , Estenose da Valva Pulmonar/terapia , Adolescente , Adulto , Criança , Estudos de Coortes , Síndrome de Cornélia de Lange/complicações , Ecocardiografia/métodos , Feminino , Seguimentos , Cardiopatias Congênitas/complicações , Comunicação Interatrial/complicações , Doenças das Valvas Cardíacas/complicações , Humanos , Lactente , Itália/epidemiologia , Estudos Longitudinais , Masculino , Estudos Prospectivos , Estenose da Valva Pulmonar/complicações , Obstrução do Fluxo Ventricular Externo/complicações , Obstrução do Fluxo Ventricular Externo/terapia , Adulto JovemRESUMO
The development of children who have syndromes with mental retardation and/or language delay can be worsened by sensorineural or conductive hearing loss (HL). Given the existing scarcity of data, we investigated the prevalence of otitis media with effusion and/or HL in 50 children with Cornelia de Lange syndrome (CdLS) aged 1-18 years, and its impact on the children's performance. The children underwent otological and audiological examinations in order to ascertain the relative frequencies of otitis media with effusion and/or hearing impairment; their demographic and clinical data were obtained by questionnaires and from information in their medical charts. Otitis media with effusion was diagnosed in 94%, and its prevalence was similar in all age groups; HL was detected in 40 children (80%). Conductive HL due to middle ear effusion was the main cause of hearing impairment alone (60%) or in combination with sensorineural deficit (20%). HL had a negative impact on performance regardless of the type. A history of routine audiological and/or otological assessments was reported by a minority of parents. Our findings indicate that otitis media with effusion and/or HL is an important feature of children with CdLS and may negatively affect their performance. Careful follow-up throughout childhood is necessary to detect and treat any hearing loss in children with CdLS in order to minimize its impact on performance.
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Síndrome de Cornélia de Lange/complicações , Síndrome de Cornélia de Lange/epidemiologia , Perda Auditiva/complicações , Perda Auditiva/epidemiologia , Otite Média com Derrame/complicações , Otite Média com Derrame/epidemiologia , Adolescente , Criança , Desenvolvimento Infantil/fisiologia , Pré-Escolar , Estudos Transversais , Síndrome de Cornélia de Lange/fisiopatologia , Feminino , Perda Auditiva/fisiopatologia , Humanos , Lactente , Itália/epidemiologia , Masculino , Otite Média com Derrame/fisiopatologia , Desempenho Psicomotor/fisiologiaRESUMO
Despite the fact that the achievement of appropriate immunization coverage for routine vaccines is a priority for health authorities worldwide, vaccination delays or missed opportunities for immunization are common in children with chronic diseases. The main aim of this cross-sectional study was to evaluate immunization coverage and the timeliness of vaccination in children suffering from 3 different rare genetic diseases: Rubinstein-Taybi syndrome (RSTS), Sotos syndrome (SS), and Beckwith-Wiedemann syndrome (BWS). A total of 57 children with genetic diseases (15 with RSTS, 14 children with SS, and 28 with BWS) and 57 healthy controls with similar characteristics were enrolled. The coverage of all the recommended vaccines in children with genetic syndromes was significantly lower than that observed in healthy controls (p < 0.05 for all the comparisons). However, when vaccinated, all of the patients, independent of the genetic syndrome from which they suffer, were administered the primary series and the booster doses at a similar time to healthy controls. In comparison with parents of healthy controls, parents of children with genetic diseases were found to more frequently have negative attitudes toward vaccination (p < 0.05 for all the comparisons), mainly for fear of the emergence of adverse events or deterioration of the underlying disease. This study shows that vaccination coverage is poor in pediatric patients with RSTS, BWS, and SS and significantly lower than that observed in healthy children. These results highlight the need for educational programs specifically aimed at both parents and pediatricians to increase immunization coverage in children with these rare genetic diseases.
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Doenças Genéticas Inatas/imunologia , Pais/psicologia , Aceitação pelo Paciente de Cuidados de Saúde , Vacinação/psicologia , Vacinas/administração & dosagem , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Esquemas de Imunização , Lactente , Masculino , Pessoa de Meia-IdadeRESUMO
To evaluate vaccination coverage of children and adolescents with inborn errors of metabolism (IEMs) and the attitudes of their parents towards vaccination, the vaccination status of 128 patients with IEM and 128 age- and gender-matched healthy controls was established by consulting the official vaccination chart. In children with IEMs, compared with healthy controls, low vaccination rates and/or delays in administration were observed for pneumococcal conjugate, meningococcus C, measles, mumps, rubella, diphtheria-tetanus-pertussis-inactivated polio, Bacillus Calmette-Guerin, and influenza vaccines. Among the parents of IEM patients, vaccine schedule compliance was primarily driven by the doctors at the hospital's reference centres; among the parents of the healthy controls, compliance was driven by the primary care paediatricians. These results show that IEM patients demonstrate sub-optimal vaccination coverage. Further studies of the different vaccines in each IEM disorder and educational programmes aimed at physicians and parents to increase immunization coverage in these patients are urgently needed.
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Conhecimentos, Atitudes e Prática em Saúde , Erros Inatos do Metabolismo , Pais/psicologia , Vacinação/estatística & dados numéricos , Vacinas/administração & dosagem , Adolescente , Criança , Pré-Escolar , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Feminino , Humanos , Esquemas de Imunização , Lactente , Masculino , Vacina contra Sarampo-Caxumba-Rubéola/administração & dosagem , Erros Inatos do Metabolismo/imunologia , Pais/educação , Médicos , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacinação/psicologia , Vacinas Combinadas/administração & dosagemRESUMO
BACKGROUND: Although individual occurrence is rare, syndromic obesity with mental retardation has been reported in conjunction with 140 different diseases. CASE PRESENTATION: The patient was born at term after a pregnancy complicated by threatened miscarriage. A diagnosis of Bardet-Biedl syndrome (BBS; OMIM #209900) was made in another hospital when she was 8 years old, but other clinical problems emerged subsequently. She came to our attention for the first time when she was 14 years old. The clinical picture, characterized by the presence of ophthalmological, renal, endocrinological, and liver disorders associated with a peculiar weight growth pattern, was more suggestive for Alström syndrome (ALMS; OMIM #203800); consequently, a genetic study was performed. Genetic analysis revealed a novel compound heterozygous frameshift mutation on exon 8 of ALMS1 (c. [3251_3258delCTGACCAG] and c. [6731delA]), which has not previously been described. CONCLUSION: Early onset of retinal degeneration associated with obesity represents a diagnostic challenge in paediatric and genetic practice, although the absence of skeletal abnormalities and developmental delay could help in addressing the clinical diagnosis. Confirmation of clinical suspicion by genetic analysis has been diriment in this case, since only a single gene is known to cause ALMS.
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Predisposição Genética para Doença , Obesidade/complicações , Degeneração Retiniana/etiologia , Adolescente , Diagnóstico Diferencial , Feminino , Testes Genéticos , Humanos , Obesidade/genética , Degeneração Retiniana/diagnóstico , Degeneração Retiniana/genética , SíndromeRESUMO
BACKGROUND: A bleeding diathesis is a common feature of Noonan syndrome, and various coagulation abnormalities have been reported. Platelet function has never been carefully investigated. METHODS: The degree of bleeding diathesis in a cohort of patients with Noonan syndrome was evaluated by a validated bleeding score and investigated with coagulation and platelet function tests. If ratios of prothrombin time and/or activated partial thromboplastin time were prolonged, the activity of clotting factors was measured. Individuals with no history of bleeding formed the control group. RESULTS: The study population included 39 patients and 28 controls. Bleeding score was ≥2 (ie, suggestive of a moderate bleeding diathesis) in 15 patients (38.5%) and ≥4 (ie, suggestive of a severe bleeding diathesis) in 7 (17.9%). Abnormal coagulation and/or platelet function tests were found in 14 patients with bleeding score ≥2 (93.3%) but also in 21 (87.5%) of those with bleeding score <2. The prothrombin time and activated partial thromboplastin time were prolonged in 18 patients (46%) and partial deficiency of factor VII, alone or in combination with the deficiency of other vitamin K-dependent factors, was the most frequent coagulation abnormality. Moreover, platelet aggregation and secretion were reduced in 29 of 35 patients (82.9%, P < .01 for all aggregating agents). CONCLUSIONS: Nearly 40% of patients with the Noonan syndrome had a bleeding diathesis and >90% of them had platelet function and/or coagulation abnormalities. Results of these tests should be taken into account in the management of bleeding or invasive procedures in these patients.
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Transtornos Hemorrágicos/sangue , Transtornos Hemorrágicos/diagnóstico , Transtornos Hemostáticos/sangue , Transtornos Hemostáticos/diagnóstico , Síndrome de Noonan/sangue , Síndrome de Noonan/diagnóstico , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Tempo de Tromboplastina Parcial , Agregação Plaquetária/fisiologia , Testes de Função Plaquetária , Tempo de Protrombina , Adulto JovemRESUMO
OBJECTIVE: Cornelia de Lange syndrome (CdLS) is a rare multisystem disorder in which hearing loss (HL) has been reported. However, no data are available concerning the association between audiological findings, clinical severity score and genotype. METHODS: The study involved 44 pediatric patients aged 1-18 years with a confirmed diagnosis of CdLS, all of whom underwent a full otolaryngological and audiological examination. The presence of NIPBL and SMC1 mutations was also evaluated. RESULTS: According to the severity of clinical phenotypes, 12 (27.3%) children were mild, 15 (34.1%) were moderate and 17 (38.6%) were severe. Thirty-eight children (86%) had OME. Eight children had normal hearing, including one (12.5%) with a severe phenotype. Bilateral sensorineural hearing loss (SNHL) was diagnosed in 10 children (22.7%): the degree of HL was severe in 8 (80%), all with a severe phenotype. Conductive hearing loss (CHL) was present in 26 patients (59.1%), of whom 8 (30.8%) had a severe phenotype. A severe phenotype was more prevalent among the patients with moderate to severe HL (10/16, 62.5%) than among those with slight/mild HL or normal hearing (7/28, 25.0% p=0.013). NIPBL mutations were detected in 22 patients (50%): 13 (59.1%) with truncating mutations, four (18.2%) with missense mutations, and five (22.7%) with splicing mutations. The frequency of NIPBL truncating mutations was similar in the children with SNHL and those with CHL, whereas this kind of mutation was not found in children with normal hearing. CONCLUSION: Together with SNHL, CHL is an important cause of HL in children with CdLS, and can be associated with a severe phenotype. Moreover, CHL can be associated with NIPBL mutations, particularly truncating mutations. These results highlight the importance of the early identification of audiological problems in children with CdLS and their precise genetic characterization.