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Background The aim of our study is to compare two groups of celiac patients: the first one in which diagnosis was based on the New 2012 ESPGHAN criteria, and the second one based on the 1991 Revised Criteria in order to find relevant difference for sex, M/F ratio, age at diagnosis, clinical features at the onset, presence and prevalence of concomitant autoimmune disorders. Methods Our study involves 61 patients having the CD onset from February 2013 to February 2020. The patients who received diagnosis according to the New 2012 ESPGHAN Criteria were enrolled in group 1. The patients who received diagnosis according to the Revised 1991 Espghan Criteria were enrolled in group 2. Prevalence of comorbidities was analysed through chi-square test. Results In group 1 the prevalence of comorbidities such as IDDM and thyroiditis was of 53%, while in group 2 was only of 24%. Analysing the difference of the IDDM prevalence between the two groups we found a relevant difference. In the same way also the prevalence of thyroiditis was significantly different. In group 1, male patients, in particular, seem to have a higher incidence of CD related autoimmune disorders. Conclusions An increased prevalence of IDDM, thyroiditis and JIA in the first group shows that the new diagnostic criteria could expose patients to a greater lengthy of disease activity responsible for the onset of such comorbidities. Further studies should be carried out on more numerous samples of patient in order to confirm this data.

Background Tumors are rare in neonatal age. Congenital mesoblastic nephroma (CMN) is a usually benign renal tumor observed at birth, or in the first months of life. It may also be identified prenatally, and associated with polyhydramnios leading to preterm delivery. Effective treatment is surgical in most cases, consisting in total nephrectomy. In literature, very few studies report on the neonatal management of such a rare disease, and even less are those describing its uncommon complications. Cases presentation We report on two single-center newborns affected with CMN. The first patient is a preterm female baby, born at 30+1 weeks of gestation (WG) due to premature labor, with prenatal (25 WG) identification of an intra-abdominal fetal mass associated with polyhydramnios. After that clinical stability, weight gain, instrumental (computed tomography, CT, showing a 4.8 x 3.3 cm left renal neoformation) and histological/molecular characterization of the lesion (renal needle biopsy picture of classic CMN with ETV6-NTRK3 translocation) were obtained, a left nephrectomy was performed at 5 weeks of chronological age. The following clinical course was complicated by intestinal obstruction due to bowel adherences formation, and then by an enterocutaneous fistula, requiring multiple surgical approaches including transitory ileo- and colostomy, before the conclusive anastomoses intervention. The second patient is a 17-day-old male term baby, coming to our observation due to postnatal evidence of palpable left abdominal mass (soon defined through CT, showing a 7.5 x 6.5 cm neoformation in the left renal lodge), feeding difficulties, and poor weight gain. He then developed hypertension and hypercalcemia, needing intravenous diuretic treatment and which regressed after nephrectomy (histological diagnosis of cellular CMN with ETV6-NTRK3 fusion), performed at day 26. In neither case was chemotherapy added. Both patients have been included in multidisciplinary follow-up, and presently show regular growth and neuromotor development, normal renal function and no local/systemic recurrences or other gastrointestinal/urinary disorders. Conclusions The finding of a fetal abdominal mass should prompt suspicion of CMN, especially if it is associated with polyhydramnios, and alert obstetricians and neonatologists also for the risk of preterm delivery. Although being a usually benign condition, CMN may be associated with neonatal systemic-metabolic or postoperative complications. High-level surgical expertise, careful neonatological intensive care, and histopathological/cytogenetic-molecular definition are the cornerstones for the optimal management of patients. This should also include an individualized follow-up, oriented to early detection of any possible recurrences or associated anomalies, and to improve the quality of life of these children and their families.

Background: In Sicily, the first wave of COVID-19 showed a low epidemic impact in paediatric population, while the second and the third waves had a higher impact on clinical presentation of COVID-19 in children and a significantly higher severe outcome in patients with multisystem inflammatory syndrome in children (MIS-C), with a frequent life-threatening progression. Methods: We describe a cohort of 22 Sicilian children (11 M; 11 F; age: 1.4-14 years), presenting with clinical features compatible with MIS-C. Patients with negative swab had a history of recent personal or parental infection. Results: The following diagnostic criteria were detected: fever (100%); cheilitis and/or pharyngeal hyperaemia (86%); latero-cervical lymphadenitis (82%); rash (73%); abdominal pain and/or vomiting and/or diarrhoea (64%); conjunctivitis (64%); hands and feet oedema (18%). 59% showed cardiac involvement (6 pericardial effusion; 8 mitral valve insufficiency; 4 insufficiency of two valves; 3 coronary artery lesions CAL)). In all the patients, treatment was started within 72 hours after the admission, with IVIG (2 g/Kg/dose), methylprednisolone (2mg/Kg/day in 73% of patients; 30 mg/Kg/day for 3 days, followed by 2 mg/Kg/day in 27% of patients). 2 patients were treated with enoxaparin. TSS was described in 2 patients, who received additionally vasoactive drugs, albumin, diuretics. Cardiac involvement evolved into the complete resolution of lesions in most of the patients. All the patients were included in a follow-up, to investigate on clinical outcome and resolution of organ involvement. Cardiac valve insufficiency persisted only in 18% of children, CAL persisted only in 33% of children with coronary involvement, however without the evolution into aneurisms. Conclusions: The preferred treatment strategy was more aggressive at the diagnosis of MIS-C, to block the cytokine cascade. Most of our patients, in fact, received a first-line treatment with IVIG and steroids. This approach could explain the favourable prognosis, the rapid restoring of cardiac function also in patients with MAS or shock, and the good outcome during the 10 months follow-up in all the patients.

Background Osteopathia Striata with Cranial Sclerosis (OS-CS), also known as Horan-Beighton Syndrome, is a rare genetic disease; about 90 cases have been reported to date. It is associated with mutations (heterozygous for female subjects and hemizygous for males) of the AMER1 gene, located at Xq11.2, and shows an X-linked pattern of transmission. Typical clinical manifestations include macrocephaly, characteristic facial features (frontal bossing, epicanthal folds, hypertelorism, depressed nasal bridge, orofacial cleft, prominent jaw), hearing loss and developmental delay. Males usually present a more severe phenotype than females and rarely survive. Diagnostic suspicion is based on clinical signs, radiographic findings of cranial and long bones sclerosis and metaphyseal striations, subsequent genetic testing may confirm it. Case presentation Hereby, we report on a female newborn with frontal and parietal bossing, narrow bitemporal diameter, dysplastic, low-set and posteriorly rotated ears, microretrognathia, cleft palate, and rhizomelic shortening of lower limbs. Postnatally, she manifested feeding intolerance with biliary vomiting and abdominal distension. Therefore, in the suspicion of bowel obstruction, she underwent surgery, which evidenced and corrected an intestinal malrotation. Limbs X-ray and skull computed tomography investigations did not show cranial sclerosis and/or metaphyseal striations. Array-CGH analysis revealed normal findings. Then, a target next generation sequencing (NGS) analysis, including the genes involved in skeletal dysplasias, was performed and revealed a de novo heterozygous nonsense mutation of the AMER1 gene. The patient was discharged at 2 months of age and included in a multidisciplinary follow-up. Aged 9 months, she now shows developmental and growth (except for relative macrocephaly) delay. The surgical correction of cleft palate has been planned. Conclusions Our report shows the uncommon association of intestinal malrotation in a female newborn with OS-CS. It highlights that neonatologists have to consider such a diagnosis, even in absence of cranial sclerosis and long bones striations, as these usually appear over time. Other syndromes with cranial malformations and skeletal dysplasia must be included in the differential diagnosis. The phenotypic spectrum is wide and variable in both genders. Due to variable X-inactivation, females may also show a severe and early-onset clinical picture. Multidisciplinary management and careful, early and long-term follow-up should be offered to these patients, in order to promptly identify any associated morbidities and prevent possible complications or adverse outcomes.

BackgroundCat eye syndrome (CES) is a rare chromosomal disease, with estimated incidence of about 1 in 100,000 live newborns. The classic triad of iris coloboma, anorectal malformations, and auricular abnormalities is present in 40% of patients, and other congenital defects may also be observed. The typical associated cytogenetic anomaly relies on an extra chromosome, derived from an inverted duplication of short arm and proximal long arm of chromosome 22, resulting in partial trisomy or tetrasomy of such regions (inv dup 22pter-22q11.2).Case presentationWe report on a full-term newborn, referred to us soon after birth. Physical examination showed facial dysmorphisms, including hypertelorism, down slanted palpebral fissures, and dysplastic ears with tragus hypoplasia and pre-auricular pit. Ophthalmologic evaluation and heart ultrasound identified left chorioretinal and iris coloboma and ostium secundum type atrial septal defect, respectively. Based on the suspicion of cat eye syndrome, a standard karyotype analysis was performed, and detected an extra small marker chromosome confirming the CES diagnosis. The chromosomal abnormality was then defined by array comparative genome hybridization (a-CGH, performed also in the parents), which identified the size of the rearrangement (3 Mb), and its de novo occurrence. Postnatally, our newborn presented with persistent hypoglycemia and cholestatic jaundice. Endocrine tests revealed congenital hypothyroidism, cortisol and growth hormone (GH) deficiencies, which were treated with replacement therapies (levotiroxine and hydrocortisone). Brain magnetic resonance imaging, later performed, showed aplasia of the anterior pituitary gland, agenesis of the stalk and ectopic neurohypophysis, confirming the congenital hypopituitarism diagnosis. She was discharged at 2 months of age, and included in a multidisciplinary follow-up. She currently is 7 months old and shows a severe global growth failure, and developmental delay. She started GH replacement treatment, and continues oral hydrocortisone, along with ursodeoxycholic acid and levothyroxine, allowing an adequate control of glycemic and thyroid profiles as well as of cholestasis.ConclusionsCES phenotypic spectrum is wide and highly variable. Our report highlights how among the possible associated endocrine disorders, congenital hypopituitarism may occur, leading to persistent hypoglycemia and cholestasis. These patients should be promptly assessed for complete hormonal evaluations, in addition to major malformations and midline anomalies. Early recognition of such defects is necessary to decrease fatal events, as well as short and long-term related adverse outcomes.

BackgroundGenetic diseases are chronic conditions with relevant impact on the lives of patients and their families. In USA and Europe it is estimated a prevalence of 60 million affected subjects, 75% of whom are in developmental age. A significant number of newborns are admitted in the Neonatal Intensive Care Units (NICU) for reasons different than prematurity, although the prevalence of those with genetic diseases is unknown. It is, then, common for the neonatologist to start a diagnostic process on suspicion of a genetic disease or malformation syndrome, or to make and communicate these diagnoses. Many surveys showed that the degree of parental satisfaction with the methods of communication of diagnosis is low. Poor communication may have short and long-term negative effects on health and psychological and social development of the child and his family. We draw up recommendations on this issue, shared by 6 Italian Scientific Societies and 4 Parents’ Associations, aimed at making the neonatologist's task easier at the difficult time of communication to parents of a genetic disease/malformation syndrome diagnosis for their child. MethodsWe used the method of the consensus paper. A multidisciplinary panel of experts was first established, based on the clinical and scientific sharing of the thematic area of present recommendations. They were suggested by the Boards of the six Scientific Societies that joined the initiative: Italian Societies of Pediatrics, Neonatology, Human Genetics, Perinatal Medicine, Obstetric and Gynecological Ultrasound and Biophysical Methodologies, and Pediatric Genetic Diseases and Congenital Disabilities. To obtain a deeper and global vision of the communication process, and to reach a better clinical management of patients and their families, representatives of four Parents' Associations were also recruited: Italian Association of Down People, Cornelia de Lange National Volunteer Association, Italian Federation of Rare Diseases, and Williams Syndrome People Association. They worked from September 2019 to November 2020 to achieve a consensus on the recommendations for the communication of a new diagnosis of genetic disease.ResultsThe consensus of experts drafted a final document defining the recommendations, for the neonatologist and/or the pediatrician working in a fist level birthing center, on the first communication of genetic disease or malformation syndrome diagnosis. Although there is no universal communication technique to make the informative process effective, we tried to identify a few relevant strategic principles that the neonatologist/pediatrician may use in the relationship with the family. We also summarized basic principles and significant aspects relating to the modalities of interaction with families in a table, in order to create an easy tool for the neonatologist to be applied in the daily care practice. We finally obtained an intersociety document, now published on the websites of the Scientific Societies involved.ConclusionsThe neonatologist/pediatrician is often the first to observe complex syndromic pictures, not always identified in the prenatal period. It is necessary for him to know the aspects of genetic diseases related to communication and bioethics, as well as the biological and clinical ones, which together outline the cornerstones of the multidisciplinary care of these patients. This consensus provide practical recommendations on how to make the first communication of a genetic disease /malformation syndrome diagnosis. The proposed goal is to make easier the informative process, and to implement the best practices in the relationship with the family. A better doctor-patient/family interaction may improve health outcomes of the child and his family, as well as reduce legal disputes with parents and the phenomenon of defensive medicine.

BACKGROUND Alternating Hemiplegia of Childhood (AHC) is an uncommon and complex disorder characterized by age of onset before 18 months, recurrent hemiplegia of one or either sides of the body or quadriplegia. Neurological comorbidities observed in two couples of AHC affected children are here reported together with data drawn by literature review. Results of genetic analysis obtained in the probands are also discussed. Developmental delay, epilepsy, tonic or dystonic spells, nystagmus and autonomic manifestations are frequently reported. AHC is mainly caused by mutations in ATP1A3 gene, and to a lesser extent in ATP1A2 gene.CASE PRESENTATION Clinical and genetic findings of a couple of twins and a couple of siblings affected by AHC from two different Italian families were deeply examined. Intrafamilial clinical variability was shown in the present cases. A pathogenic variant rs606231437 in ATP1A3 gene was detected in twins. For the affected siblings of family 2, the genetic results showed that the older brother and the healthy father shared a novel variant of GRIN2A (c.3175T>A) gene, and two missense mutations in SCNIB (rs150721582) and KCNQ2 (rs771211103) genes. In the younger brother was found only the GRIN2A variant.CONCLUSIONS Developmental delay, epileptic seizures and motor dysfunction are features frequently associated to paroxysmal hemiplegic attacks. Hemiplegic episode is only a sign even if the most remarkable of several neurological comorbidities in AHC carriers. The comparison of molecular analysis among the four probands brings out how the genetic framework is not recurrent, but may result from an unexpected greater genetic heterogeneity.

BackgroundHypohidrotic Ectodermal Dysplasia (HED) is a genetic disorder which affects structures of ectodermal origin. X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common form of disease. XLHED Is characterized by hypotrichosis, hypohydrosis and hypodontia. The cardinal features of classic HED become obvious during childhood. Identification of a hemizygous EDA pathogenic variant in an affected male confirms the diagnosis. Case PresentationWe report on a male newborn with the main clinical characteristics of the X-linked HED including hypotrichosis, hypodontia and hypohidrosis. Gene panel sequencing identified a new hemizygous missense variant of uncertain significance (VUS) c.1142G >C (p.Gly318A1a) in the EDA gene, located on the X chromosome and inherited from the healthy mother. ConclusionDespite the potential functional impact of VUS remains uncharacterized, our goal is to evaluate the clinical potential consequences of missense VUS on EDA gene. Given the proband’s phenotype compatibility with classic HED, it is reasonable to attribute a causative role to the variant found in hemizygosis in the gene EDA. The present case demonstrates that this novel VUS could broaden the spectrum of genes mutations involved in the HED phenotype.

Background: The last months were signed by the pandemic diffusion of COVID-19, with the need to minimize the inflow of children and adolescents affected by chronic diseases into the hospitals. Otherwise, paediatricians had to limit visits and to consider a new setting for febrile children.Patients were assisted by telephonic consultations guaranteed by the paediatricians of free choice and by the paediatric specialists. However, patients frequently needed a direct specialistic evaluation in the case of flares, abnormal laboratory parameters and adverse reactions to drugs.Another frequent question was the differential diagnosis of febrile episodes, to distinguish a recurrent fever, linked to autoinflammation, from an infectious disease.We proposed to paediatricians of free choice in west-Sicily a questionnaire about difficulties met in the follow-up of children with rheumatologic diseases, autoinflammatory syndromes, congenital hypothyroidism.Results: 55 questionnaires were collected: the most frequent recorded conditions were periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA syndrome) and Familial Mediterranean Fever; Juvenile Idiopathic Arthritis, congenital hypothyroidism.All the paediatricians needed specialistic support to adequately control flares, adjustment of drugs dosage.Conclusions: Patients and paediatricians need a specialistic support for the follow-up and to reach a good compliance to treatment.This period characterized by smart working, telemedicine, strategies to monitor remotely the patients, can find the winning strategy in the approach of the “Co-working”, a new cooperation between hospital and paediatricians of free choice, in the global follow-up of paediatric chronic diseases.

Introduction Autosomal recessive polycystic kidney disease (ARPKD; MIM#263200) is one of the most frequent pediatric renal cystic diseases, with an incidence of 1:20,000. It is caused by mutations of the PKHD1 gene, on chromosome 6p12. The clinical spectrum is highly variable, ranging from late-onset milder forms to severe perinatal manifestations. The management of newborns with severe pulmonary insufficiency is challenging, and causes of early death are sepsis or respiratory failure. In cases of massive renal enlargement, early bilateral nephrectomy and peritoneal dialysis may reduce infant mortality. However, there is no conclusive data on the role of surgery, and decision-making is driven by patient’s clinical condition and expertise of the center. Patient presentation We hereby describe a preterm female newborn with perinatal, rapid and bilateral, abnormal growth of both kidneys, respiratory failure and initial signs of liver disease. She was subsequently confirmed to be affected by a rare and severe homozygous mutation of the PKHD1 gene, inherited from both her consanguineous parents. Our patient died 78 days after birth, due to a fungal sepsis which worsened her respiratory insufficiency. Conclusions This patient report shows some of the clinical and ethical issues of neonatal ARPKD, and the need of multidisciplinary approach and good communication with the family. Target next generation sequencing (NGS) techniques may guide and support clinicians, as well as guarantee to these patients the most appropriate clinical management, avoiding unnecessary and/or disproportionate treatments.

Background: Antimicrobial resistance in Neonatal Intensive Care Unit (NICU) patients is a threat, due to the large use of antimicrobial treatment and invasive devices in fragile babies.Since 2014 an active surveillance program of multidrug-resistant Gram-negative bacteria (MDR-GNB) carriage is in place in the five NICUs of Palermo, Italy. In 2017 an increase in the prevalence of MDR-GNB and in particular of extended-spectrum β-lactamases-producing Klebsiella pneumoniae (ESBL-KP) was observed in “Civico” hospital NICU. Aim: To estimate the impact of a coordinated intervention strategy in achieving long-lasting reduction of MDR-GNB prevalence in the NICU.Methods: Rectal swabs were obtained monthly and processed to detect MDR-GNB using standard methods. MDR-GNB were characterized by pulsed-field gel electrophoresis (PFGE). From November 2017 the following intervention measures were applied: a) two-months strengthening of sample collection; b) stakeholders’ meetings; c) improvement of prevention measures and antimicrobial policy. Prevalence of MDR-GNB carriage observed in the 12 months before and in the 24 months after intervention were compared by chi-square test. Risk factors for MDR-GNB carriage in a subgroup of patients were identified by a multivariate logistic regression model. Findings: During the strengthened microbiological surveillance MDR-GNB and ESBL-KP were detected in rectal swabs (34.8%; 23.2%), nasal swabs (24.6%; 14.5%), oral swabs (14.5%; 5.4%), milk samples (32.1%; 17.9%), soother swabs (30.8%; 17.9%) and from a sub-intensive room surface. Thirteen ESBL-KP strains isolated from clinical and environmental samples showed identical PFGE patterns. ESBL-KP was detected no more until June 2018. No MDR-GNB isolate was detected for three months. Prevalence of MDR-GNB and ESBL-KP carriage after intervention significantly decreased compared to the previous year (20.6% vs 62.2 %; pConclusions: MDR-GNB broadly circulate in NICU setting and can colonize different body sites and spread by various vehicles. A coordinated strategy of multiple interventions with active cooperation between epidemiologists and clinicians in the NICU can effectively reduce their circulation and in particular the carriage of most dangerous ESBL-KP strains.