In Tandem Intragenic Duplication of Doublesex and Mab-3-Related Transcription Factor 1 (DMRT1) in an SRY-Negative Boy with a 46,XX Disorder of Sex Development.

Disorders of sexual development (DSDs) encompass a group of congenital conditions associated with atypical development of internal and external genital structures. Among those with DSDs are 46,XX males, whose condition mainly arises due to the translocation of SRY onto an X chromosome or an autosome. In the few SRY-negative 46,XX males, overexpression of other pro-testis genes or failure of pro-ovarian/anti-testis genes may be involved, even if a non-negligible number of cases remain unexplained. A three-year-old boy with an SRY-negative 46,XX karyotype showed a normal male phenotype and normal prepubertal values for testicular hormones. A heterozygous de novo in tandem duplication of 50,221 bp, which encompassed exons 2 and 3 of the Doublesex and Mab-3-related transcription factor 1 (DMRT1) gene, was detected using MPLA, CGH-array analysis, and Sanger sequencing. Both breakpoints were in the intronic regions, and this duplication did not stop or shift the coding frame. Additional pathogenic or uncertain variants were not found in a known pro-testis/anti-ovary gene cascade using a custom NGS panel and whole genome sequencing. The duplication may have allowed DMRT1 to escape the transcriptional repression that normally occurs in 46,XX fetal gonads and thus permitted the testicular determination cascade to switch on. So far, no case of SRY-negative 46,XX DSD with alterations in DMRT1 has been described.

How E-cigarettes and vaping can affect asthma in children and adolescents.

PURPOSE OF REVIEW: Electronic nicotine delivery systems such as e-cigarettes are commonly felt to be harmless devices when compared to traditional cigarettes. However, an increasing number of studies support the biological plausibility for the potential detrimental effects of vaping on the respiratory mucosa. To date, few human studies have been carried out on adult vapers showing a reduction in lung function testing, especially in those with asthma, whereas the effects of vaping on children and adolescents have not been elucidated so far. RECENT FINDINGS: Several cross-sectional, national, population-based studies on large groups of adolescents have been carried out showing an association between vape exposure and self-reported asthma diagnosis and/or respiratory symptoms in this age group. The effects of second and third-hand exposure together with those of active and passive exposure in pregnancy, are almost completely unknown. SUMMARY: This review outlines recent data on the potential effects of vaping on asthma, focusing on vape composition, reported effects on the respiratory mucosa, available data in adolescents, and reasons behind the current vaping epidemic. The evidence so far available both in animals and humans suggests that vaping is not harmless, and its exposure should be limited in children and adolescents, especially when affected by asthma.

The evolving epidemiology of acute gastroenteritis in hospitalized children in Italy.

Few data are available on the prevalence and features of acute gastroenteritis (AGE) in hospitalized children in Italy, where specific rotavirus vaccines were introduced into the national vaccination plan in 2017. To evaluate vaccination effects on AGE epidemiology, we analysed data from children aged ≤ 18 years admitted for AGE at the University Hospital of Pisa in 2019, comparing them with those recorded in 2012. Demographical, clinical, diagnostic, and treatment data were collected reviewing medical records and were therefore compared. In 2019 and 2012, 86 (median age 2.5 years [IQR 1.4-5.9]) and 85 children (median age 2.3 years [IQR 1.3-5.1]) were respectively admitted with AGE. The most common symptoms were diarrhoea and vomiting; decreased skin turgor was more frequent in 2019 (54% and 34% respectively, p = 0.01). Viral infections were more common than bacterial ones; in 2019, a decrease in rotavirus infections (67% and 22%, p = 0.003) and an increase in adenovirus infections (50% and 10%, p = 0.002) and in the number of patients with negative stool testing (58% and 39%, p = 0.04) were found.Conclusions: Viral infections are the leading cause of AGE in hospitalized children in Italy. The introduction of rotavirus vaccines did not reduce the number of hospitalizations per year. Adenovirus and other non-routinely screened viruses may be undergoing a selection process making them common causative agents for AGE. What is Known: • Rotavirus is the leading cause of acute severe gastroenteritis in children worldwide, especially < 5 years of age. • The introduction of specific vaccines may be changing its epidemiology. • Few data are available on acute gastroenteritis in hospitalized children in Italy. What is New: • Viral infections are the leading cause of acute gastroenteritis in hospitalized children in Italy. • Specific vaccines are reducing rotavirus infections, but adenovirus and other non-routinely screened viruses may be undergoing a selection process making them common causative agents for gastroenteritis.

Potential effects of E-cigarettes and vaping on pediatric asthma.

Asthma is the most common chronic disease in childhood and exposure to tobacco smoke has been long recognized as a risk factor for its onset as well as for exacerbations and poor disease control. Since the early 2000s, electronic cigarettes have been marketed worldwide as a non-harmful electronic alternative to combustible cigarettes and as a device likely to help stop smoking, and their use is continuously rising, particularly among adolescents. However, several studies have shown that vape contains many different well-known toxicants, causing significant cytotoxic and pro-inflammatory effects on the airways in-vitro and in animal models. In humans, a variety of harmful lung effects related to vaping, ranging from bronchoconstriction to severe respiratory distress has been already reported. To investigate the potential effects of vaping in pediatric asthma, we searched relevant published studies in the MEDLINE/PubMed database by combining the adequate Medical Subject Headings terms and key words. At the end of our study selection process, five cross-sectional studies focusing on electronic cigarettes use in adolescents and self-reported asthma and/or other respiratory symptoms, one study focusing on the effects of electronic cigarettes second-hand exposure and one case report were retrieved. These preliminary data support a likely detrimental effect of vaping in asthmatic adolescents. Currently available evidence supports that electronic cigarettes are a potential threat to respiratory health, particularly in adolescents with asthma. High-quality studies on larger population assessing the long-term effects of vape exposure, are urgently needed.

Hyaluronic acid for the treatment of airway diseases in children: Little evidence for few indications.

BACKGROUND: Hyaluronic acid (HA) is major physiological component of the extracellular matrix, which, in its high molecular weight form (HMW-HA) has anti-inflammatory properties. The diffusion of many different medical devices for inhalation therapy containing HA has led to an increase in their prescription, also in children. Here, we systematically review the published evidence on the efficacy and safety of HA for the treatment of upper and lower airway diseases in childhood. METHODS: Relevant published studies (randomized controlled trials) for the efficacy of HA inhalation in children with upper airways diseases, asthma, cystic fibrosis (CF), and non-CF bronchiectasis were searched in Pubmed, Scopus, and Web of Knowledge databases by combining the adequate Medical Subject Headings terms and keywords, with no limit for the year of publication. RESULTS: We identified seven relevant publications for upper airways diseases, one for asthma, and five for CF, while we found no clinical trial including children with non-CF bronchiectasis. Meta-analysis was not conducted due to the heterogeneity of the included studies. CONCLUSIONS: The evidence of HA efficacy in the treatment of the upper and lower airways is still limited in children. Available data suggest that inhaled HMW-HA could be useful in the treatment of recurrent upper respiratory infections and chronic or recurrent inflammation of the middle ear and adenoids as well as of the lower airways in cystic fibrosis in association with hypertonic saline solution. Studies on larger populations and on the different formulations and nebulization methods, especially in pediatric age, are urgently needed.

Adolescent Gynecomastia due to Minimal Androgen Resistance Syndrome: A Case Report and Literature Review.

A 14-year-old boy with a 46,XY karyotype and persistent breast-3-stage gynecomastia is reported. The reproductive axis was investigated by standard laboratory methods and the androgen receptor (AR) gene was sequenced. Also, a literature review of phenotypes associated with the AR genetic variant p.Pro392Ser was performed. The boy presented with height in the upper normal range (+1.9 SDS) and normal body mass index (-0,3 SDS); pubertal development was PH5/G4 (mean testicular volume 15 mL; 0 SDS). Laboratory findings were normal for age and sex, except aromatization index (0.09; reference range 0.03-0.07). Analysis of the AR gene showed the single nucleotide variant c.1174C>T (p.Pro392Ser) in exon 1, leading to the diagnosis of minimal androgen insensitivity syndrome (AIS). This genetic variant is reported in other 8 patients with AIS and is associated with variable clinical phenotypes ranging from complete to partial and minimal AIS. To the best of our knowledge, this is the first adolescent in whom the p.Pro392Ser mutation is associated with isolated persistent gynecomastia. The underlying reason of phenotypic variability due to this AR mutation remains unknown. Persistent gynecomastia due to minimal AIS has been reported in few additional males with variable AR mutations. Since fertility troubles may occur in adult men with minimal AIS, early diagnosis can allow optimizing the clinical management.