Ospedale Microcitemico

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Background: Children with Down syndrome (DS) are at high risk for a broad spectrum of otorhinolaryngologic (ENT) disorders, including hearing impairment, obstructive sleep apnea (OSA), dysphagia, and language delay. These conditions often coexist and interact with the neurodevelopmental and anatomical features of DS, requiring early identification and coordinated management. Despite the clinical burden, ENT involvement in DS remains under-characterized and inconsistently addressed in care pathways. Methods: A narrative review was conducted to provide an integrative overview of ENT manifestations in pediatric patients with DS. A literature search was performed in PubMed, Scopus, and Web of Science, covering studies published between 1979 and 2025. Articles were included if they addressed ENT disorders in children with DS and met clinical relevance criteria. A total of 45 studies were selected and analysed by study design, focus, and contribution to diagnostic or therapeutic frameworks. Results: The majority of included studies were observational in nature, covering key domains such as conductive hearing loss, chronic otitis media with effusion, sleep-disordered breathing, and feeding/swallowing dysfunction. Several articles emphasized the importance of early audiologic and polysomnographic screening. Gaps in standardization and accessibility of multidisciplinary ENT care were consistently reported. A proposed framework for integrated evaluation is discussed. Conclusions: ENT manifestations in pediatric DS are frequent, multifactorial, and clinically impactful. A multidisciplinary, anticipatory model of care is essential for timely diagnosis and targeted intervention. This review highlights the need to formalize ENT pathways within comprehensive care protocols for children with DS.

Marfan Syndrome (MS) is a connective tissue disorder, an autosomal dominant condition mostly caused by variants in the FBN1 gene, which encodes for fibrillin-1 protein. Anomalies in the gene lead to a wide variety of clinical manifestations, including disorders of the cardiac, ocular and musculoskeletal system. We present a case of a child belonging to a Sardinian family of four generations, with a novel variant found in the FBN1 gene. To include this novel missense FBN1 variant into genetic counselling for Marfan Syndrome and to discuss its genotypic-phenotypic correlation. Firstly, the proband was diagnosed with Marfan Syndrome using 2020 Revised Ghent Criteria, and she then underwent genetic testing using Next Generation sequencing. The NGS revealed a novel heterozygous missense variant (c.2348A>G) in the FBN1 gene, in exon 20. This genetic variant caused a missense substitution of a serine residue with an arginine residue in the position 783 of Fibrillin-1 protein. The variant was then evaluated in the other family members, and was eventually only found in symptomatic individuals, regardless of the severity of their phenotype, demonstrating the segregation with MS; furthermore, it showed complete penetrance with the disease. Our results suggest that this variant is responsible for MS and it therefore should be included in genetic diagnoses and counselling discussion.

ContextThere has been concern about a potential increase in the incidence or severity of coronavirus disease 2019 (COVID-19) in individuals with adrenal insufficiency (AI). Data on the course of SARS-CoV-2 infection in AI children are lacking.ObjectiveEvaluate whether children with AI are more susceptible to the infection or are at risk of severe COVID-19.MethodsIn this multicenter, retrospective study among 1143 children with AI, 148 contracted SARS-CoV-2 (112 with primary, 36 with secondary AI) and were evaluated for severity and outcomes of infection, along with 74 control subjects with normal adrenal function.ResultsThe prevalence of COVID-19 in the AI cohort was 12.9%, not increased compared to pediatric Italian population in the same period. The severity was not increased in AI subjects and was classified as follows in patients vs controls: asymptomatic in 14.9% vs 10.8%; paucisymptomatic in 33.8% vs 37.8%; mild in 45.3% vs 45.9%; severe in 3.4% vs 2.7%; critical in 2.7% vs 2.7%. Among those with severe COVID, 4 patients with AI (2.7%) and 3 controls (4%) developed pneumonia while 3 patients with PAI (2%) and 2 controls (2.7%) developed multisystem inflammatory syndrome (P not statistically significant). Only 5 patients (3.4%) experienced an adrenal crisis during a severe COVID-19. The hospitalization rate was the same in patients vs controls (9.5%). All subjects completely recovered, and no COVID-related deaths were documented.ConclusionOur findings do not indicate that AI is associated with increased susceptibility to SARS-CoV-2 infection or higher risk for severe COVID-19 in children.

Background: Houge-Janssens syndrome 1 is a condition with onset in early childhood caused by heterozygous pathogenic variants in the PPP2R5D gene, which encodes a B56 regulatory subunit of the serine/threonine protein phosphatase 2A (PP2A). There is evidence that the PP2A-PPP2R5D complex is involved in regulating the phosphatidylinositol 3-kinase (PI3K)/AKT signalling pathway, which is crucial for several cellular processes, including the pathogenesis and progression of haemangiomas. Case presentation: We report the first PPP2R5D-related neurodevelopmental disorder case from Sardinia, a child with transient hypoglycaemia, facial dysmorphisms, and multiple haemangiomas. Whole Exome Sequencing analysis confirmed the clinical suspicion, detecting the presence of the de novo missense variant c.592G>A in the PPP2R5D gene. Conclusions: Haemangiomas have never been linked to the syndromic phenotype of the PPP2R5D-associated disorder. The close correlation between the PP2A enzyme and the PI3K/AKT signalling pathway suggests the possible correlation between its dysfunction and activation of haemangiogenesis. Our report highlights a possible link between the PPP2R5D-related disorder and altered angiogenesis, characterizing diffuse haemangiomas as a possible novel phenotypic trait of this condition.

Data on iron overload status and change thresholds that can predict mortality in patients with transfusion-dependent β-thalassemia (TDT) are limited. This was a retrospective cohort study of 912 TDT patients followed for up to 10years at treatment centers in Italy (median age 32years, 51.6% female). The crude mortality rate was 2.9%. Following best-predictive threshold identification through receiver operating characteristic curve analyses, data from multivariate Cox-regression models showed that patients with Period Average Serum Ferritin (SF) > 2145 vs ≤ 2145ng/mL were 7.1-fold (P < 0.001) or with Absolute Change SF > 1330 vs ≤ 1330ng/mL increase were 21.5-fold (P < 0.001) more likely to die from any cause. Patients with Period Average Liver Iron Concentration (LIC) > 8 vs ≤ 8mg/g were 20.2-fold (P < 0.001) or with Absolute Change LIC > 1.4 vs ≤ 1.4mg/g increase were 27.6-fold (P < 0.001) more likely to die from any cause. Patients with Index (first) cardiac T2* (cT2*) < 27 vs ≥ 27ms were 8.6-fold (P < 0.001) more likely to die from any cause. Similarly, results at varying thresholds were identified for death from cardiovascular disease. These findings should support decisions on iron chelation therapy by establishing treatment targets, including safe iron levels and clinically meaningful changes over time.

There are only a few nationwide studies on boys with central precocious puberty (CPP) and the last Italian study is a case series of 45 boys that dates back to 2000. We aimed to evaluate the causes of CPP in boys diagnosed during the last 2 decades in Italy and the relative frequency of forms with associated central nervous system (CNS) abnormalities on magnetic resonance imaging (MRI) compared to idiopathic ones. We performed a national multicenter retrospective study collecting data from 193 otherwise normal healthy boys with a diagnosis of CPP. Based on MRI findings, the patients were divided into: Group 1, no CNS abnormalities; Group 2, mild abnormalities (incidental findings) unrelated to CPP; and Group 3, causal pathological CNS abnormalities. The MRI findings show normal findings in 86%, mild abnormalities (incidental findings) in 8.3%, and causal pathological CNS abnormalities in 5.7% of the cases. In Group 3, we found a higher proportion of patients with chronological age at diagnosis < 7 years (P = .00001) and body mass index greater than +2 SDS (P < .01). Gonadotropin-releasing hormone analogue therapy was started in 183/193 subjects. The final height appeared in the range of the target height in all groups and in 9 patients in whom the therapy was not started. In our study on a large nationwide cohort of boys referred for precocious puberty signs, the percentage of forms associated with CNS abnormalities was one of the lowest reported in the literature.

Objective: Persistence of a fetal thickened Nuchal translucency (NT), one of the most sensitive and specific individual markers of fetal disorders, is strongly correlated with the possibility of a genetic syndrome, congenital infections or other malformations. Thickened NT can also be found in normal pregnancies. Several of its pathophysiological aspects still remain unexplained. Metabolomics could offer a fresh opportunity to explore maternal-foetal metabolism in an effort to explain its physiological and pathological mechanisms. Design: A population-based prospective cohort study (2020-2021). Setting: Cagliari, Italy. Population and Methods: Thirty-nine samples of amniotic fluids were collected from women who underwent amniocentesis due to an increased risk of aneuploidy, divisible into 12 foetuses with an enlarged nuchal translucency (&gt;NT) and 27 controls (C). Samples were analyzed using a Gas Chromatography Mass Spectrometry platform. Subsequently, multivariate and univariate statistical analyses and Receiver Operator Curves (ROC) were performed to find a specific metabolic pattern of &gt;NT class. Results: The supervised model analysis showed robust statistical parameters (R2X=0.2, R2Y=0.76, Q2=0.4, p&lt;0.002). The correlation between the complete metabolic profile and clinical parameters were evaluated (NT showed an R2=0.75, p=0.002, foetal crown-rump length showed R2=0.65, p=0.002, pregnancy Associated Plasma Protein-A showed R2=0.60). Nine metabolites significantly differing between &gt;NT foetuses and C were detected: 2-hydroxybutyric acid, 3-hydroxybutyric, 1,5 Anydro-Sorbitol, cholesterol, erythronic acid, fructose, malic acid, threitol and threonine which were linked to altered pathways involved in altered energetic pathways. Conclusion: Through the metabolomics approach it was possible to identified a specific metabolic fingerprint of the fetuses with &gt;NT.