Case report: Gastroenterological management in a case of cardio-facio-cutaneous syndrome

Backgroundcardio-facio-cutaneous syndrome is a rare genetic disorder affecting less than 900 people in the world. It is mainly characterized by craniofacial, dermatologic and cardiac defects, but also gastroenterological symptoms may be present, ranging from feeding difficulties to gastroesophageal reflux and constipation.In this report we describe a case of this syndrome characterized by severe feeding and growth difficulties, with a particular focus on the management of gastroenterological complications.Case presentationthe patient was a caucasian male affected by Cardio-Facio-Cutaneous syndrome who presented feeding difficulties already a few hours after birth. These symptoms worsened in the following months and lead to a complete growth arrest and malnutrition. He was first treated with a nasogastric tube placement. Subsequently, a laparoscopic Nissen fundoplication and a laparoscopic Stamm gastrostomy were performed. The child was fed with nocturnal enteral nutrition and diurnal oral and enteral nutrition. Eventually the patient resumed feeding validly and regained adequate growth.Conclusionthis paper aims to bring to light a complex rare syndrome that infrequently comes to the attention of the pediatricians and whose diagnosis is not always straightforward. We also highlight the possible complications under a gastroenterologic point of view. Our contribution can be helpful to the pediatrician in the first diagnostic suspect of this syndrome. In particular, it is worth highlighting that -in an infant with Noonan-like features- symptoms like suction or swallowing problems, vomiting and feeding difficulties should orient towards the diagnosis of a Cardio-facio-cutaneous syndrome. It is also important to stress that its related gastroenterological issues may lead to severe growth failure and therefore the role of the gastroenterologist is key to manage supplemental feeding and to establish whether a nasogastric or gastrostomic tube placement is necessary

Atypical cardiac defects in patients with RASopathies: Updated data on CARNET study

Background: RASopathies are a set of relatively common autosomal dominant clinically and genetically heterogeneous disorders. Cardiac outcomes in terms of mortality and morbidity for common heart defects (such as pulmonary valve stenosis and hypertrophic cardiomyopathy) have been reported. Nevertheless, also Atypical Cardiac Defects (ACDs) are described. The aim of the present study was to report both prevalence and cardiac outcome of ACDs in patients with RASopathies. Methods: A retrospective, multicentric observational study (CArdiac Rasopathy NETwork—CARNET study) was carried out. Clinical, surgical, and genetic data of the patients who were followed until December 2019 were collected. Results: Forty‐five patients out of 440 followed in CARNET centers had ACDs. Noonan Syndrome (NS), NS Multiple Lentigines (NSML) and CardioFacioCutaneous Syndrome (CFCS) were present in 36, 5 and 4 patients, respectively. Median age at last follow‐up was 20.1 years (range 6.9–47 years). Different ACDs were reported, including mitral and aortic valve dysfunction, ascending and descending aortic arch anomalies, coronary arteries dilation, enlargement of left atrial appendage and isolated pulmonary branches diseases. Five patients (11%) underwent cardiac surgery and one of them underwent a second intervention for mitral valve replacement and severe pericardial effusion. No patients died in our cohort until December 2019. Conclusions: Patients with RASopathies present a distinct CHD spectrum. Present data suggest that also ACDs must be carefully investigated for their possible impact on the clinical outcome. A careful longitudinal follow up until the individuals reach an adult age is recommended

Cardiac defects, morbidity and mortality in patients affected by RASopathies. CARNET study results

BACKGROUND: RASopathies are developmental disease caused by mutations in genes encoding for signal transducers of the RAS-MAPK cascade. The aim of the present study was to provide a comprehensive description of morbidity and mortality in patients with molecularly confirmed RASopathy. METHODS: A multicentric, observational, retrospective study was conducted in seven European cardiac centres participating to the CArdiac Rasopathy NETwork (CARNET). Clinical records of 371 patients with confirmed molecular diagnosis of RASopathy were reviewed. Mortality was described as crude mortality, cumulative survival and restricted estimated mean survival. Multivariable regression analysis was used to assess the impact of mutated genes on number of interventions and overall prognosis. RESULTS: Cardiac defects occurred in 80.3% of cases, almost half of them underwent at least one intervention. Overall, crude mortality was 0.29/100 patients-year. Cumulative survival was 98.8%, 98.2%, 97.7%, 94.3%, at 1, 5, 10, and 20 years, respectively. Restricted estimated mean survival at 20 years follow-up was 19.6 years. Ten patients died (2.7% of the entire cohort; 3.4% of patients with cardiac defect). Patients with hypertrophic cardiomyopathy (HCM) and age < 2 years or young adults, as well as subjects with biventricular obstruction and PTPN11 mutations had a higher risk of cardiac death. CONCLUSIONS: The risk of intervention was higher in individuals with Noonan syndrome and pulmonary stenosis carrying PTPN11 mutations. Overall, mortality was relatively low, even though the specific association between HCM, biventricular outflow tract obstructions and PTPN11 mutations appeared to be associated with early mortality, including immediate post-operative events and sudden death

Data on cardiac defects, morbidity and mortality in patients affected by RASopathies. CARNET study results

A comprehensive description of morbidity and mortality in patients affected by mutations in genes encoding for signal transducers of the RAS-MAPK cascade (RASopathies) was performed in our study recently published in the International Journal of Cardiology. Seven European cardiac centres participating to the CArdiac Rasopathy NETwork (CARNET), collaborated in this multicentric, observational, retrospective data analysis and collection. In this study, clinical records of 371 patients with confirmed molecular diagnosis of RASopathy were reviewed. Cardiac defects, crude mortality, survival rate of patients with 1) hypertrophic cardiomyopathy (HCM) and age <2 years or young adults; 2) individuals with Noonan syndrome and pulmonary stenosis carrying PTPN11 mutations; 3) biventricular obstruction and PTPN11 mutations; 4) Costello syndrome or cardiofaciocutaneous syndrome were analysed. Mortality was described as crude mortality, cumulative survival and restricted estimated mean survival. In particular, with this Data In Brief (DIB) paper, the authors aim to report specific statistic highlights of the multivariable regression analysis that was used to assess the impact of mutated genes on number of interventions and overall prognosis

Acute Cardiovascular Manifestations in 286 Children With Multisystem Inflammatory Syndrome Associated With COVID-19 Infection in Europe

Background: The aim of the study was to document cardiovascular clinical findings, cardiac imaging, and laboratory markers in children presenting with the novel multisystem inflammatory syndrome associated with coronavirus disease 2019 (COVID-19) infection. Methods: This real-time internet-based survey has been endorsed by the Association for European Paediatric and Congenital Cardiologists Working Groups for Cardiac Imaging and Cardiovascular Intensive Care. Children 0 to 18 years of age admitted to a hospital between February 1 and June 6, 2020, with a diagnosis of an inflammatory syndrome and acute cardiovascular complications were included. Results: A total of 286 children from 55 centers in 17 European countries were included. The median age was 8.4 years (interquartile range, 3.8-12.4 years) and 67% were boys. The most common cardiovascular complications were shock, cardiac arrhythmias, pericardial effusion, and coronary artery dilatation. Reduced left ventricular ejection fraction was present in over half of the patients, and a vast majority of children had raised cardiac troponin when checked. The biochemical markers of inflammation were raised in most patients on admission: elevated C-reactive protein, serum ferritin, procalcitonin, N-terminal pro B-type natriuretic peptide, interleukin-6 level, and D-dimers. There was a statistically significant correlation between degree of elevation in cardiac and biochemical parameters and the need for intensive care support (P<0.05). Polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 was positive in 33.6%, whereas immunoglobulin M and immunoglobulin G antibodies were positive in 15.7% cases and immunoglobulin G in 43.6% cases, respectively, when checked. One child in the study cohort died. Conclusions: Cardiac involvement is common in children with multisystem inflammatory syndrome associated with the Covid-19 pandemic. The majority of children have significantly raised levels of N-terminal pro B-type natriuretic peptide, ferritin, D-dimers, and cardiac troponin in addition to high C-reactive protein and procalcitonin levels. In comparison with adults with COVID-19, mortality in children with multisystem inflammatory syndrome associated with COVID-19 is uncommon despite multisystem involvement, very elevated inflammatory markers, and the need for intensive care support.info:eu-repo/semantics/publishedVersio

Adenoid assessment in paediatric patients: the role of flexible nasal endoscopy.

Adenoid hypertrophy is the most common cause of nasal obstruction in paediatric patients. Over the years, various methods to assess the adenoid size were proposed such as the posterior rhinoscopy and the radiological examination of the nasopharynx. Nasal endoscopy was introduced for children in the 80&#x0027;s, and nowadays this is a known and diffuse method in routine practice. The purpose of this article is to describe the personal experience in the assessment of the adenoid size in children, with a particular regard to the flexible nasal endoscopy, and to analyse the literature reports. The personal technique is described in performing nasal endoscopy in paediatric patients, reporting advantages and possible disadvantages of the procedure. A retrospective analysis was conducted on 6036 children since 1999 to 2010. In most cases children fully collaborated to complete the exam. No major or minor complications (such as nose bleedings or other traumatic injuries) were observed. No topical intranasal decongestant, local or general anaesthesia were used in our series. In our opinion, nasal endoscopy in children is a reliable, safe, accurate, easily tolerated and dynamic diagnostic method to assess the adenoid size

Semi-supine Exercise Stress Echocardiography in Children and Adolescents: Feasibility and Safety

Although exercise stress echocardiography (ESE) is a well-validated technique in adult population, its use in children is quite limited. We aimed to assess the feasibility, the safety and the reproducibility of ESE, using on-line scanning in semi-supine cyclo-ergometer protocol in a large pediatric population. Between July 2008 and January 2013, 42 patients (mean age 14 ± 3) were evaluated with a bicycle ESE performing 50 studies. ESE was successfully performed and well tolerated by all patients. None of the patients presented with adverse effects of stress-induced ischemia. HR was 82 ± 13 at rest, and 153 ± 19.1 during peak exercise. Among 544 views analyzed for grading of image quality, the visualization was optimal in 473 (87 %), suboptimal in 39, and inadequate in 32 (6 %). 37 tests were performed in patients with congenital or acquired coronary abnormality. Regional wall motion abnormalities (RWMA) were revealed in nine cases (24 %). The agreement between the two different observers showed a K index of 0.7276 (95 % CI 0.6497-0.8055) for the image quality and a K index of 0.5125 (95 % CI 0.4782-0.5468) for the RWMA analysis. Among ten patients with hypertrophic cardiomyopathy, we were able to demonstrate the new comparison of significant left ventricular outflow tract gradient (≥30 mmHg) during exercise in three patients (30 %). Bicycle stress echocardiography performed by on-line scanning during exercise is a feasible, safe, and reproducible modality in children. Further data to assess its diagnostic accuracy are, however, needed. Stress echocardiography provides a dynamic assessment of the myocardial structure and function under conditions of physiologic or pharmacologic stress

FEF(25-75) might be a predictive factor for bronchial inflammation and bronchial hyperreactivity in adolescents with allergic rhinitis.

Allergic rhinitis and asthma are closely associated. Bronchial hyperreactivity (BHR) is a pathophysiological characteristic of asthma. Allergic inflammation is characterized by eosinophilic infiltrate and may by indirectly assessed by exhaled nitric oxide (FeNO). Forced expiratory flow between 25 percent and 75 percent of vital capacity (FEF25-75) may predict BHR in adult patients with allergic rhinitis. The aim of this study was to evaluate the presence of BHR in a large group of adolescents with allergic rhinitis and whether FEF25-75 might be related with BHR and FeNO. Methods 150 adolescents with allergic rhinitis were enrolled. Clinical examination, skin prick test, spirometry, methacholine challenge, and FeNO were performed in all patients. Results Severe BHR is quite frequent in allergic adolescents. Impaired FEF25-75 values (such as less than 65 percent of predicted) constitute a relevant predictive factor for severe BHR (OR 4.4). FeNO levels were significantly related with BHR. Conclusion This study provides evidence that impaired FEF25-75 values might predict severe BHR and BHR is related with FeNO in adolescents. Therefore, BHR should be suspected in adolescents with low FEF25-75 values