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Background: Childhood obesity represents a major public health issue worldwide. Evidence showed the need to implement prevention strategies mainly focused on lifestyle habits. Sleep hygiene is a variable of great interest and this review systematically examined the effects of sleep duration in increasing childhood obesity risk., Methods: A systematic literature review was conducted from December 2023 to February 2024. Study selection and data extraction procedures were performed in accordance with Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines and Statement, and risk of publication bias was assessed by the Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies., Results: Original works in English were eligible for review and eleven studies that met the inclusion criteria were included. Studies collected were heterogeneous in terms of duration, sample characteristics, hours of sleep manipulation, anthropometric and hematological parameters collected, therefore it was not possible to perform a meta-analysis. A narrative synthesis of the reported evidence highlighted the impact of sleep duration above all on food intake, eating habits and hormone levels and consequently on the risk of childhood obesity development., Conclusion: This finding suggests the need to consider sleep hygiene as a modifiable lifestyle habit like diet and physical activity, in order to early prevent childhood obesity. Poor sleep hygiene can significantly contribute to weight gain and exacerbation of metabolic disorders linked to childhood obesity. Although more rigorous studies are needed, clinicians need to be aware of the role of sleep hygiene in reducing childhood obesity risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Porri, Luppino, Aversa, Corica, Valenzise, Messina, Pepe, Morabito, La Rosa, Lugarà, Abbate, Coco, Franchina, Lanzafame, Toscano, Li Pomi, Cavallaro and Wasniewska.)

Background: The increase in childhood obesity rates represents a serious public health problem. The project "EpPOI: Education to prevent childhood obesity" is aimed at a multidisciplinary approach to raise awareness of the importance of preventing childhood obesity through lifestyle education., Methods: Two actions by experts were performed: an intervention with children in schools and a meeting for both parents and school staff. Participants completed a questionnaire structured as a Likert scale., Results: The sample size was 96 people, and awareness of the childhood obesity problem as well as the need for obesity prevention was high among respondents. We also found great interest among participants in having more information on pediatric nutrition and physical activity, with a positive correlation with age. Furthermore, the multivariate regression model configured interest in having more information on nutrition and physical activity as an independent and statistically significant predictor of awareness of childhood obesity as a current issue., Conclusions: The results highlight the need to act on childhood obesity through lifestyle prevention strategies early in life.

Adiposity rebound (AR) refers to the second rise of the body mass index (BMI) curve that usually occurs between six and eight years of age. AR timing has a significant impact on patients' health: early AR (EAR), usually before the age of five, is considered to be the earliest indicator of obesity and its related health conditions later in life. Many studies have evaluated factors that can be predictors of EAR, and identified low birth weight and gestational weight gain as novel predictors of EAR, highlighting the role of the intrauterine environment in the kinetics of adiposity. Furthermore, children with breastfeeding longer than 4 months have been found to be less likely to have an EAR, whereas children born to advanced-age mothers, high maternal BMI had a higher risk of having an EAR. Some differences were found in the timing of AR in boys and girls, with girls being more likely to have EAR. The aim of this review is to answer the following three questions: 1) Which are the prenatal and perinatal factors associated with increased risk of EAR? Is gender one of these? 2) Which are the outcomes of EAR in childhood and in adulthood? 3) Which measures can be taken in order to prevent premature AR?, (© 2024. The Author(s).)

Purpose: Turner syndrome (TS) is the most common sex chromosomal abnormality found in female subjects. It is a result of a partial or complete loss of one of the X chromosomes. Short stature is a hallmark of TS. Attainment of adult height (AH) within the normal range for height within the general female population represents the usual long-term goal of growth hormone (GH) treatment. The aim of this systematic review was to understand the efficacy of GH therapy on AH of patients with TS., Methods: The literature review yielded for analysis 9 articles published from 2010 to 2021. Using the data from this literature search, the goal was to answer 5 questions: (1) What is the efficacy of GH on AH of girls with TS?; (2) Is AH influenced by the age at initiation of GH treatment?; (3) What is the optimal dose of GH to improve AH?; (4) Can the timing of either spontaneous or induced puberty influence AH?; and (5) Can the karyotype influence AH in patients with TS?, Findings: GH therapy and adequate dose could enable patients with TS to achieve appropriate AH compared with the possible final height without therapy. The greatest increase in height during GH therapy occurs in the prepubertal years, and if therapy is continued to AH, there is no further increase. Furthermore, karyotype did not show a predictive value on height prognosis and did not affect the outcome of GH administration or the height gain in girls with TS., Implications: Even if GH therapy is safe, close monitoring is indicated and recommended. Further evidence is needed to understand what other parameters may influence AH in patients undergoing GH therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Turner Syndrome (TS) is the most common female sex chromosome aneuploidy in females, and patients may present with hypergonadotropic hypogonadism due to gonadal dysgenesis. Timing and modalities of pubertal induction in these patients is still a matter of debate. Aim of this review was to focus on the latest update on pubertal induction in TS. Based on literature data, the following practical approach to this issue is recommended. Pubertal induction should begin between 11 and 12 years of age, starting with low doses of estradiol to preserve height potential. Transdermal 17β-Estradiol (17β-E2) could represent the first-choice induction regimen as it is more physiologic compared to an oral regimen and avoids the first-pass mechanism in the liver. In the case of poor compliance, administration of oral 17β-E2 or ethinyl estradiol could be offered. Incremental dose increases, approximately every 6 months, can contribute to mimic normal pubertal progression until adult dosing is reached over a 2- to 3-year period. Progestin should be added once breakthrough bleeding occurs or after 2 to 3 years of estrogen therapy or if ultrasound shows a mature uterus with thick endometrium. Treatment needs to be individualized and monitored by clinical assessment in relation to patient compliance and satisfaction. Well-designed prospective randomized clinical trials aimed to identify the best estrogen regimen for pubertal induction in TS girls are needed.

Introduction: Despite advances in the management of type 1 diabetes (T1D), there is an increasing incidence of skin reactions related to diabetes devices such as patch pumps and glucose sensors. Aim of the present study was to assess the prevalence of dermatological complications in pediatric patients with T1D using technological devices., Methods: Online survey regarding skin reactions related to the use of patch pumps and/or glucose sensors was administered to families of children and adolescents (0-17 years) with T1D. Data were collected on demographic characteristics, duration of diabetes, and clinical features of dermatological complications if present., Results: Our study population consisted of 139 patients (female 51.8%) aged 11.1 ± 3.3 years. More than half (51.1%) experienced skin reactions due to patch pumps or glucose sensors. Dermatological complications were mainly caused by continuous glucose monitoring (56.3% of total). Timing of appearance of dermatological reactions varied from a few days to several months after the introduction of the device. The application of hypoallergenic barrier bandages was the most frequently adopted measure to solve the issue., Conclusions: Our study confirmed high frequency of dermatological complications among pediatric patients with type 1 diabetes. Well-designed studies are awaited to provide clear recommendations to minimize the burden of skin issues related to technological devices.

In the era of precision medicine, allergen immunotherapy (AIT) represents a landmark for the management of IgE-mediated allergic diseases. AIT is recognized as a potentially curative therapy and is currently accepted and routinely prescribed worldwide. However, there are still unmet needs. The efforts of researchers are aimed at implementing current immunotherapeutic strategies to improve the standard care of patients suffering from IgE-mediated respiratory allergic diseases. In addition, over the horizon, the most realistic option is the active treatment of IgE-mediated food allergy with oral immunotherapy. Preclinical studies and clinical trials are increasingly conducted to identify innovative forms of AIT administration, potential biomarkers, alternative immunotherapeutic allergen candidates, and new adjuvants. Telemedicine could represent a further emerging field capable of supporting health service delivery and improving clinical outcomes of AIT., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Aims: Aim of our observational study was to assess the prevalence of allergic contact dermatitis among children and adolescents with type 1 diabetes who use technological devices for diabetes treatment and its management. Secondary outcome was to identify possible clinical and/or demographic variables that could be associated to contact dermatitis., Methods: Among a total of 215 patients using insulin pumps and/or glucose sensors followed-up at our Pediatric Diabetes Centre between January and September 2018, 64 patients were enrolled and 42 (19 male and 23 female) completed the study. Demographic and clinical features of the study population were statistically analysed. All the patients underwent patch testing with specific allergens belonged to resin and acrylate classes., Results: Eighteen patients experienced skin reactions suggestive of allergic contact dermatitis, demonstrating a prevalence of 8.4%. None of the demographic or clinical variables were associated to skin reactions. Colophonium was the most identified sensitizing allergen (87.5% of the cases)., Conclusions: The rate of sensitization to allergens included into diabetes devices among pediatric patients is higher than commonly assumed. Well-designed studies are needed to better investigate the association between type 1 diabetes and allergic contact dermatitis. Moreover, we suggest that manufactures should supply detailed information about adhesives in order to avoid dermatological complications and consequently a worsening of disease management and patients' quality of life., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In the past few years, the increasing use of devices for diabetes treatment, such as continuous subcutaneous insulin infusion pumps, flash glucose monitoring, continuous glucose monitoring systems, sensor-augmented pumps, and automated insulin delivery devices, has resulted in important improvements in disease management. Meanwhile, the longer a patient uses a device, the greater the likelihood of developing a skin reaction. Allergic contact dermatitis is the most frequently described skin side effect caused by adhesive tapes contained in the insulin infusion sets or glucose sensor sets and used to connect these devices to the body. We describe 18 patients, followed up at our Pediatric Diabetes Centre, who experienced dermatological complications due to diabetes device use from January 2018 to December 2018. All the patients were patch tested with allergens from a "standard" series and from a "plastics and glues" series. Patch tests resulted positive in 66.7% of patients. Colophonium was the most frequently isolated sensitizing allergen (41.1% of cases). It is a complex mixture of > 100 compounds derived from pine trees. Colophonium is commonly used, in both unmodified and modified forms, as a fast-acting adhesive for industrial, medical, or other commercial uses. Its presence in the adhesive of the insulin sets and glucose sensors was confirmed by the manufacturer of some devices brand. On the basis of our results, we stress the importance of contacting manufacturers for product information. We also highlight that there should be stricter legal restrictions to label medical adhesives, even if only small amounts of colophonium are used.

Maturity onset diabetes of the young (MODY) accounts for up to 4% of all cases of diabetes in pediatric patients. MODY is usually characterized by autosomal dominant inheritance, impaired insulin secretion, and an average age at diagnosis of 18-26 years. Mutations in the hepatocyte nuclear factor 1-alpha (HNF1A), glucokinase, hepatocyte nuclear factor 4-alpha, and hepatocyte nuclear factor 1-beta genes are the mutations most frequently observed in cases of MODY. We herein report a case of HNF1A-MODY characterized by an early onset of diabetes. Genetic investigations revealed a de novo heterozygous substitution, N237D (HNF1A c.709A>G), in exon 3 of the HNF1A gene. Our case supports the hypothesis that de novo mutations are more frequent than expected. This recent evidence may suggest that conventional clinical diagnostic criteria for MODY should be revised and personalized according to the individual patient.

Objectives: The objectives were to evaluate (1) the metabolic profile and cardiometabolic risk in overweight/obese children at first assessment, stratifying patients according to severity of overweight and age; and (2) to investigate the relationship between family history (FH) for obesity and cardiometabolic diseases and severity of childhood obesity., Methods: In this cross-sectional, retrospective, observational study, 260 children (139 female), aged between 2.4 and 17.2 years, with overweight and obesity were recruited. Data regarding FH for obesity and cardiometabolic diseases were collected. Each patient underwent clinical and auxological examination and fasting blood sampling for metabolic profile. Homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride-to-high-density lipoprotein cholesterol ratio, and atherogenic index of plasma were calculated. To evaluate the severity of obesity, children were divided into two groups for BMI standard deviation (SD) ≤2.5 and BMI SD >2.5. Moreover, study population was analyzed, dividing it into three groups based on the chronological age of patient (<8, 8-11, >11 years)., Results: BMI SD was negatively correlated with chronological age ( p  < 0.005) and significantly higher in the group of children <8 years. BMI SD was positively associated with FH for obesity. Patients with more severe obesity (BMI SD >2.5) were younger ( p  < 0.005), mostly prepubertal, presented a significantly higher HOMA-IR ( p  = 0.04), and had a significantly higher prevalence of FH for arterial hypertension, type 2 diabetes mellitus, and coronary heart disease than the other group., Conclusion: (1) Family history of obesity and cardiometabolic diseases are important risk factors for precocious obesity onset in childhood and are related to the severity of obesity. (2) Metabolic profile, especially HOMA-IR, is altered even among the youngest obese children at first evaluation. (3) Stratification of obesity severity, using BMI SD, is effective to estimate the cardiometabolic risk of patients.

Background: Children affected by neurodevelopmental disability could experience early pubertal changes at least 20 times more than the general population. Limited data about central precocious puberty (CPP) among children affected by cerebral palsy (CP) are available., Methods: This is a longitudinal, observational, retrospective, case-control study involving 22 children affected by CPP and CP (group A), 22 paired with CP but without CPP (group B), and 22 children with CPP without CP. Auxological, biochemical, and instrumental data were collected at diagnosis of CPP and at 2 follow-up visits., Results: No differences were detected between groups A (at baseline) and B. At diagnosis of CPP, height SDS adjusted for target height (H-TH SDS) was significantly reduced in A than in C (-0.63 ± 1.94 versus 1.56 ± 1.38), while basal LH and oestradiol levels were significantly elevated in A than in C. During follow-up, despite an effective treatment, growth impairment deteriorated in A than in C (Δ H-SDS from diagnosis of CPP to last follow-up: -0.49 ± 0.91 versus 0.21 ± 0.33, p = 0.023)., Conclusions: Diagnosis of CPP could be partially mislead in CP due to growth failure that got worse during follow-up despite therapy. CPP in CP seems to progress rapidly along time supporting the hypothesis of a more intense activation of hypothalamic-pituitary-gonadal-axis in these patients.

Aims: We aimed at evaluating a standard multiplex ligation-dependent probe amplification (MLPA) probe set for the detection of aneuploidy to diagnose Turner syndrome (TS). We first fixed an MLPA ratio cutoff able to detect all cases of TS in a pilot TS group. We then tested this value on a second group of TS patients and a short-stature population to measure specificity and sensitivity., Methods: 15 TS patients with X mosaicism or X structural abnormalities (Pilot TS Group), 45 TS karyotype-assessed patients (TS Group), and 74 prepubertal female patients with apparent idiopathic short stature (Short-Stature Group) were enrolled. All subjects underwent MLPA and karyotype analysis. In the TS and Short-Stature Groups, MLPA testing was performed in blind., Results: The choice of an MLPA threshold ratio of 0.76 for at least 1 probe allowed us to detect all TS cases, including mosaicisms. Sensitivity and specificity were 100% (CI 95%, 0.92-1) and 88.89% (CI 95%, 0.79-0.94), respectively. The positive predictive value was 88.5%, and the negative predictive value was 100%. MLPA detected the presence of Y chromosome material in 2 patients., Conclusion: MLPA is an accurate and inexpensive tool to screen for TS in girls with short stature. A customized MLPA kit may be useful for the screening of an even larger population., (© 2016 S. Karger AG, Basel.)

Aim: To prospectively investigate, during a 5-year follow-up, whether the prognosis of thyroid function with Hashimoto thyroiditis (HT) is different in euthyroid girls with Turner syndrome (TS) than in euthyroid girls without TS., Design: In 66 TS girls and 132 non-TS girls with euthyroid HT and similar thyroid functional test results at HT diagnosis, we followed up the evolution of thyroid status over time., Results: At the end of follow-up, the TS girls exhibited higher TSH levels, lower fT4 levels, and lower prevalence rates of both euthyroidism and subclinical hypothyroidism, but higher prevalence rates of both overt hypothyroidism and hyperthyroidism, irrespective of the karyotype., Conclusions: An association with TS is able to impair the long-term prognosis of thyroid function in girls with HT. Such an effect occurs irrespective of thyroid functional test results at HT diagnosis and is not necessarily linked with a specific karyotype., (© 2016 S. Karger AG, Basel.)

Aim: To follow-up for 5 years thyroid status evolution in 127 girls with mild (TSH 5-10 mU/l) subclinical hypothyroidism (SH) of different etiologies., Patients: The population was divided into two age-matched groups of 42 and 85 girls with either idiopathic (group A) or Hashimoto's thyroiditis (HT)-related SH (group B). Group B was in turn divided into three subgroups, according to whether SH was either isolated or associated with Turner syndrome (TS) or Down syndrome (DS)., Results: At the end of follow-up the rate of girls who became euthyroid was higher in group A (61.9% vs 10.6%), whereas the rates of patients who remained SH (55.3% vs 26.2%), became overtly hypothyroid (30.6% vs 11.9%) or required levothyroxine (l-T4) therapy (63.5% vs 23.8%) were higher in group B. Among the girls of group B, the risk of remaining SH or developing overt hypothyroidism was higher in the subgroups with TS or DS than in those with isolated HT., Conclusions: Long-term prognosis of mild and idiopathic SH is frequently benign, even though a l-T4 treatment may be needed throughout follow-up in almost a quarter of cases; long-term prognosis is different in the girls with either idiopathic or HT-related SH; and the association with either TS or DS impairs the outcome of HT-related SH., (© 2015 European Society of Endocrinology.)

Subjects with hypergonadotropic hypogonadism due to Turner's syndrome show low cortical mineral density, osteoporosis and risk of fractures. It is not clear if this bone fragility derives from chromosomal abnormalities or is the result of inadequate bone formation due to estrogen deficiency. The aim of this study was to investigate the cellular mechanisms underlying bone fragility in subjects with Turner's syndrome before induction of puberty and after hormonal replacement therapy (HRT). For this purpose, we have evaluated the osteoclastogenic potential of non-fractioned and T-cell depleted cultures of peripheral blood mononuclear cells (PBMCs) belonging to girls with Turner's syndrome who had not been treated with HRT yet, girls and young women who were on HRT and age-matched controls. Untreated subjects showed high FSH serum levels, whereas the other subjects displayed normal FSH serum levels. T-cell immunophenotype was analyzed through flow cytometry. Biochemical and DXA analyses were performed. Spontaneous osteoclastogenesis in non-fractioned and T-cell depleted cultures of PBMC belonging to girls with high FSH levels was more evident than in cultures of subjects with normal FSH levels. In the former, osteoclastogenesis was sustained by monocytes expressing high levels of c-fms, TNF-α and RANK, and T-cells producing high RANKL and TNF-α; in the latter it was supported by T-cells expressing high RANKL levels. CD4(+)CD25(high) T-cells were reduced in all subjects, whereas CD3(+)/CD16(+)/CD56(+) NKT-cells were increased in those with high FSH levels. High RANKL and CTX levels were detected in the sera. Bone impairment was already detectable by DXA in subjects aged under 10, although it became more evident with aging. In conclusion, our results demonstrated that bone fragility in subjects with Turner's syndrome is associated to enhanced osteoclastogenesis. This process seems to be due to high FSH serum levels before HRT, whereas it is caused by high RANKL during HRT., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Only few studies have investigated to now whether the association with Turner syndrome (TS) may affect the course of Hashimoto's thyroiditis (HT) in children. Aim of this study was to ascertain whether the presentation and long-term course of HT in TS children may be characterized by a peculiar and atypical pattern. The clinical and biochemical findings at HT diagnosis in 90 TS children (group A) were compared with those recorded in 449 girls with HT but without TS (group B); in group A patients, thyroid function tests were re-evaluated after a median time interval of 4.9 years. At HT diagnosis median TSH levels and the rate of cases presenting with a thyroid dysfunction picture were significantly lower in group A, irrespective of karyotype abnormalities. In group A only 34.8 % of the girls who had initially presented with euthyroidism remained euthyroid even at re-evaluation, whilst 67.7 % of those who had presented with subclinical hypothyroidism became overtly hypothyroid over time; also such evolutive pattern was irrespective of karyotype abnormalities. (1) In TS girls, HT presents with a milder hormonal pattern, which often deteriorates over time; (2) these biochemical features are not necessarily linked with a specific karyotype.

Objective: Primary gonadal failure may occur in most individuals with Turner syndrome (TS). Since ovaries in TS girls undergo premature apoptosis and cryopreservation of ovarian tissue is now feasible, it would be useful to identify a reliable marker of ovarian reserve in these patients. We planned to evaluate ovarian function in a group of TS patients by measuring both traditional markers and inhibin B and to compare these results with those of a control group., Study Design: We enrolled 23 patients with TS and 17 age-matched healthy girls. The median age of our TS patients was 17.6 years. Three out of the 23 patients (13%) showed spontaneous pubertal development and regular menstrual cycles; the remaining 20 (86.9%) presented with primary amenorrhea., Results: The median level of inhibin B in the TS patients with primary amenorrhea was 42 pg/mL and did not differ significantly among the different subgroups in relation to karyotype. The median inhibin B level in the control group was significantly higher than in the TS girls with primary amenorrhea (83 vs. 42 pg/mL, p<0.00001). In the three patients with TS and spontaneous menstrual cycles, the inhibin B levels were significantly higher when compared to the values of the TS girls with primary amenorrhea., Conclusion: TS patients with primary amenorrhea have significantly lower levels of inhibin B than TS girls with spontaneous puberty and healthy controls. Inhibin B does not correlate with follicle-stimulating hormone/luteinizing hormone. If our results are confirmed in further studies, inhibin B could become a first-line screening test for assessing ovarian reserve and a longitudinal marker of the possible decline of ovarian function in TS.

Unlabelled: Aim of this commentary is to summarize the salient literature news on the relationships between autoimmune thyroid diseases (ATDs) and either Down syndrome (DS) or Turner syndrome (TS).According to literature reports both Hashimoto's thyroiditis (HT) and Graves' disease (GD) are more frequent in children with DS or TS than in those without these chromosomopathies.An up-regulation of proinflammatory cytokines might be responsible for the enhanced susceptibility of TS children to ATDs, whereas a dysregulation of immune system may favor the development of ATDs in DS.In TS children biochemical presentation of HT is less severe than in peer controls. In both DS and TS GD picture at the time of diagnosis is not significantly different than in the pediatric general population.The evolution over time of GD in DS and TS does not differ from that observed in the pediatric general population, whereas the evolution of HT in both TS and DS is more severe than in girls without these chromosomopathies., Conclusions: The association with TS or DS is able to affect both epidemiology and course of ATDs by conditioning: a) an increased susceptibility to these disorders; b) a less severe biochemical presentation and a more severe evolutive pattern of HT in TS girls; c) a more severe biochemical presentation and evolution of HT in DS patients.

Background: This study was carried out because of the rarity of peripheral precocious puberty (PPP) in boys with McCune-Albright syndrome (MAS) and the lack of data on adult height of treated MAS males, treatment for this disorder being not as yet standardized., Aims: To report the adult height of a MAS boy with PPP who was treated with ketoconazole - cyproterone acetate - leuprolide depot and to describe some atypical aspects of MAS presentation and course in this boy., Case History: The case concerns a boy presenting with unilateral macroorchidism, no signs of PPP or initially isolated Sertoli cell activation and MAS mutation that subsequently also activated Leydig cells, thus inducing a change in phenotypic expression., Conclusions: a) In a MAS boy presenting with unilateral macroorchidism and no other signs of PPP, a consecutive involvement of Leydig cells may follow the initially isolated activation of Sertoli cells; b) prolonged treatment with ketoconazole - cyproterone acetate - leuprolide depot may be well tolerated and effective, as demonstrated by the very good adult height outcome recorded in our patient.

Aim: To analyze the factors that might allow an early discrimination between permanent (P) and transient (T) congenital hypothyroidism (CH)., Methods: Clinical, biochemical and imaging data of 64 children with eutopic gland, who were positively screened and treated for CH during the period 1998-2011, were retrospectively analyzed., Results: During a 3-year treatment period, the mean doses of L-thyroxine (L-T4) per kilogram of body weight at various times were significantly lower in the 46 children with T CH than in the remaining 18 with P CH. No patients with T CH had required any increment of the doses of L-T4 per kilogram of body weight to maintain normal thyroid-stimulating hormone levels over time, whereas 16/18 children with P CH during the same period had needed some dose increments (p < 0.0001)., Conclusions: (a) L-T4 requirements >4.9 µg/kg/day at 12 months or >4.27 µg/kg/day at 24 months are highly suggestive of P CH, irrespective of gland ultrasonography; (b) L-T4 requirements <1.7 µg/kg/day at 12 months or <1.45 µg/kg/day at 24 months are highly suggestive of T CH, at least in the cases with eutopic gland, and (c) the analysis of L-T4 requirements during the first years of treatment might allow an early discrimination between T and P CH in the cases with eutopic gland., (© 2015 S. Karger AG, Basel.)

Background: Allgrove's 4A syndrome determines ocular surface changes. This is the first report providing an up-to-dated analysis of the ocular surface in an affected patient., Case Presentation: An 18-years-old male Caucasian patient, with a complex progressive gait disorder and adrenal insufficiency, was referred for ophthalmic evaluation, as part of the clinical assessment. He underwent the following tests: best corrected visual acuity, tear osmolarity, tear film break-up time (BUT), corneal fluorescein staining, Schirmer's I test, lid margin assessment, corneal sensitivity, in vivo corneal confocal microscopy, conjunctival impression cytology, tonometry and fundus exam. A dry eye condition was documented by the Schirmer's I test of 0 mm/5' in both eyes, accompanied by tear hyperosmolarity, mild meibomian gland dysfunction, reduced BUT, mucus filaments in the tear film and conjunctival epithelium metaplasic changes. The corneal confocal microscopy showed the presence of activated keratocytes, while the nerve pattern was normal., Conclusions: The dry eye in this patient appears to be due to tear aqueous deficiency and can be considered as part of the 4A syndrome. The decreased tear production, resulting from a deterioration of the autonomic innervation of the lacrimal glands rather than an impaired corneal innervation, can be considered as part of the systemic autonomic dysfunction present in this disease.

Background: Epidemiological studies on the association between Turner syndrome (TS) and Graves' disease (GD) are sparse and no studies are available on the clinical course of GD in TS., Objectives: To retrospectively investigate the GD prevalence in children and young adults with TS and to compare the GD course in patients with or without TS who were followed up for 4.1 ± 0.6 and 4.5 ± 3.7 years, respectively., Design: The prevalence of GD in 408 TS patients was evaluated; presentation and evolution of GD under therapy were evaluated both in 7 patients with TS (group A) and in 89 patients without TS (group B)., Results: (a) The prevalence of GD in TS patients was 1.7%; (b) GD in TS was not associated with a specific karyotype; (c) with respect to group B patients, those of group A exhibited at presentation more advanced age, a lower fT4 level and more frequent association with other autoimmune diseases, and (d) the clinical course under methimazole therapy was not different in the two groups., Conclusions: The prevalence of GD in children and young adults with TS is 1.7% and in TS patients, GD presents later and its clinical course is not different than in those without TS.

Objective: To evaluate adult height (AH) in 25 girls with Turner syndrome (TS) who were treated from before 6 years of age for 10.0 ± 1.7 years with a fixed GH dose of 0.33 mg/kg per week., Patients and Design: After a 6-month pretreatment assessment all patients were measured 6-monthly under therapy to assess height SDS (H-SDS) and height velocity (HV) until AH achievement., Results: Following initial acceleration, HV declined after the first 4 years of therapy. At the end of the sixth year of therapy, H-SDS gain was 1.9 ± 1.1. Thereafter, H-SDS gain from baseline decreased, becoming 0.9 ± 0.9 SDS at AH achievement. Bone maturation velocity did not significantly change throughout the prepubertal period. According to Lyon standards for TS, mean AH SDS was significantly higher than pretreatment H-SDS (P<0.0001), with a mean H-SDS change of 0.9 ± 0.9. However, the prevalence of patients with AH <-2 SDS (according to Sempé standards) was close to those recorded at the start of therapy (16/25 vs 18/25). No significant differences in terms of AH were found between patients with either X monosomy or X-chromosomal abnormalities and between girls with either spontaneous or induced puberty., Conclusions: We infer that the therapeutic regimen adopted in this prospective study is sufficient to induce a significant growth acceleration during the first year, but the response waned after 6 years of treatment.

Unlabelled: The aim of the present paper is to describe a novel missense mutation (G107R) of WFS1 gene that was unexpectedly detected, in two siblings from Southern Italy, outside exon 8; a very unusual finding which has previously been reported only twice in Italian patients with Wolfram syndrome (WS). Although in Spanish pedigrees' WFS1 mutations are frequently located in exon 4, this finding is very infrequent in other pedigrees, particularly in Italian patients., Conclusions: a) our report of two siblings with one novel WSF1 mutation (G107R) expands the molecular spectrum of WS; b) this is the 3rd report of Italian patients harbouring one mutation outside exon 8 and the 2nd with one mutation in exon 4; c) on the basis of the present observations, and literature data we can infer that mutation locations outside exon 8 do not seem to be clearly associated with peculiar phenotype expressions of WFS1 gene., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Unlabelled: Klinefelter syndrome (KS) is the most frequent chromosomal aneuploidy with a prevalence of 1:500 men but it often remains a largely undiagnosed condition and only 10% of cases are identified in childhood and adolescence. We report the anamnestic, clinical and auxological findings of 14 KS patients diagnosed in paediatric age. 3/14 patients (21%) with KS were diagnosed in prenatal age by amniocentesis, 1 patient was diagnosed at birth due to genital ambiguity and the remaining 10/14 (71.4%) were diagnosed at a chronological age younger than 15 years old for a clinical picture characterized by a peculiar cognitive and behavioral pattern or genital anomalies and abnormalities of pubertal development. The classical karyotype 47 XXY was present in 10/14 subjects (72%), a mosaic form (46 XY/47 XXY) was present in 2/14 (14%) and a complex aneuploidy (48 XXYY and 48 XXXY)was present in the remaining 2/14 (14%) patients. All KS patients diagnosed in childhood and adolescence (10/14 =71.4 %) showed a stature taller than the respective target height and also the predicted final height (calculated from a chronological age older than 7 years old) and the reached final height were significantly taller than target height., Conclusion: according to our retrospective data we can assert that KS in paediatric age is characterized by a stature taller than target

Background: Cow's milk allergy is common in infancy, and total avoidance of this food is the only effective approach. In alternative, oral immunotherapy has been proposed to achieve tolerance. Once desensitization is achieved, daily intake of milk is recommended to maintain it, but this may be impractical for children/parents. We assessed whether a twice weekly maintenance regimen is effective., Methods: Children who were successfully desensitized with oral immunotherapy were randomized to two maintenance regimens for 1 year: group A had to eat 150-200 ml milk daily, group B had to eat 150-200 ml milk twice weekly. Both regimens were associated to a totally free diet. Maintenance of tolerance and adverse events were recorded during 1 year. Specific IgE, IgG4 and prick-by-prick test to milk were carried out before immunotherapy (T0), before maintenance (T1), and after 1 year (T2)., Results: Recorded episodes included asthma, oral itching, urticaria, rhinitis, abdominal pain variously combined, usually associated with concomitant illness or exercise. The episodes were 8 in group A and 9 in group B, with no difference. None of the children discontinued the feeding maintenance. Specific IgG4 increased at T1 and remained high at T2. Specific IgE and skin reactivity significantly decreased at T2. There was no difference in those parameters between the groups., Conclusion: After achieving desensitization to cow milk with oral immunotherapy, a maintenance regimen with milk given twice weekly is as effective as the daily maintenance., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

48, XXYY is a very rare sex chromosome aneuploidy, characterized by both an extra X and Y chromosome with a prevalence of 1:18,000-1:40,000. Most patients are diagnosed prenatally by cytogenetic examination of amniotic fluid, or during the first years of life because of severe developmental delay, cognitive impairment and behavioural disorders. This syndrome shares two findings with Klinefelter syndrome, namely tall stature and hypergonadotropic hypogonadism but at this time no genital anomalies have been reported in patients with this tetrasomy. We describe a 48, XXYY neonate and a clinical picture characterized by small penis, bifid scrotum, scrotal hypospadias and testes palpable in the labioscrotal folds.

Klinefelter syndrome (KS) with the classic 47,XXY karyotype is the most frequent chromosomal aneuploidy, with a prevalence of 1 in 700 men; although the classic clinical picture is well-known and easily recognizable, most patients remain undiagnosed. The rate of diagnosis during childhood is extremely low, and only 10% of cases are identified before puberty, with a subsequent rate of ascertainment during lifetime of 25%. The low rate of timely diagnosis is because most of the classical signs and symptoms of androgen deficiency appear in mid- to late adolescence but it is important to recognize that adult men with KS may show a great variability in clinical and physical features. A common, often underappreciated, element in young boys and children with KS is the characteristic cognitive and behavioral pattern. We describe 2 patients who were diagnosed at 7.1 and 10 years through a characteristic neurocognitive profile. Both of them showed low-normal scores when evaluated by tests of general intelligence and a behavioral profile characterized by immaturity, low self-esteem, and learning disabilities. Clinical examination showed tall stature and progressive growth acceleration between 5 and 7 years, and one of them had hypoplastic scrotum with monolateral cryptorchidism. To achieve the goal of an early diagnosis of KS, it is necessary to increase medical awareness of the disease and, in particular, to augment pediatricians' knowledge that during prepubertal age pathognomonic clinical features of KS are often lacking but a characteristic cognitive and behavioral pattern is commonly present.

Spinal muscular atrophy with respiratory distress (SMARD 1) is a very rare autosomal recessive motor neuron disorder that affects infants and is characterized by diaphragmatic palsy, symmetrical distal muscular weakness, muscle atrophy, peripheral sensory neuropathy and autonomic nerve dysfunction. SMARD 1 is inherited as an autosomal recessive trait and the mutations have been identified in the gene encoding immunoglobulin μ-binding protein 2 (IGHMBP2), located on chromosome 11q13. It is considered a fatal form of infantile motoneuron disease and most of the patients dies within the first 13 months of life. We present a female child with genetically confirmed SMARD 1 displaying a mild phenotype and no severe signs of respiratory involvement, typically found in this form, up to 38 months despite a diaphragmatic palsy diagnosed at 6 months of age. Therefore, our clinical observation suggests that respiratory failure is not secondary, in any case, to the diaphragmatic palsy but other pathogenetic mechanisms might be involved., (Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Background: To date, there is no agreement about the frequency or the features of thyroid abnormalities in McCune-Albright syndrome (MAS). The aim of our study was to detect thyroid abnormalities in a cohort of MAS children and adolescents and to give indications for their treatment and follow-up., Methods: In 36 patients, 22 females and 14 males, thyroid function and sonographic features of thyroid were evaluated every 6-12 months., Results: Three males and 1 female had hyperthyroidism: 2 with nodular, 2 with diffuse goiters. They were treated with methimazole (0.2-0.5 mg/kg/day) with good clinical and biochemical responses. The remaining 32 patients were euthyroid, even if 7 displayed sonographic alterations, of whom 5 had nodular goiter with nodules >1 cm, and 2 micronodular goiter. Fine-needle aspiration biopsy was performed in 2 patients with nodules >1 cm, 1 showing hemorrhagic nodule and 1 colloid cystic nodule., Conclusions: Prevalence of thyroid alterations in the studied MAS series was 31%. 64% of 11 patients with thyroid alterations had nodular goiters, with nodules >1 cm. As the onset of thyroid disease ranged from 1 to 20 years, a strict monitoring of thyroid function is recommended every 6 months. Satisfactory treatment can be obtained and maintained with antithyroid drugs., (Copyright © 2012 S. Karger AG, Basel.)

Background: There are few studies investigating the factors which may affect different biochemical presentations of Hashimoto's thyroiditis (HT) and these are frequently based on limited pediatric populations., Aims: (1) To assess the frequency of thyroid function patterns at HT diagnosis in 608 children and adolescents, and (2) to analyze the factors that affect thyroid status at diagnosis., Results: At presentation, test results showed euthyroidism in 52.1% of patients (subgroup A), overt or subclinical hypothyroidism in 41.4%, and overt or subclinical hyperthyroidism in 6.5%. The mean age of patients with thyroid dysfunctions (subgroup B) was significantly lower than that of subgroup A, and the rate of children below 10 years of age was significantly greater in subgroup B. Other variables related to thyroid function patterns were prepubertal status; association with either Down or Turner syndromes, which correlated with increased risk of thyroid dysfunctions, and association with other autoimmune diseases, which correlated with decreased risk of thyroid dysfunctions. None of the remaining factors analyzed were associated with increased risk of thyroid dysfunctions., Conclusions: Biochemical thyroid function patterns at HT presentation in childhood and adolescence are mainly conditioned by patients' age., (Copyright © 2012 S. Karger AG, Basel.)

Erythema multiforme is characterized by itching macules, papules and bullae, symmetrically distributed on the dorsum of the hands. They can follow the administration of several drugs or infections with various agents, and in particular with herpes simplex virus. The recurrent variant is very rare, especially in the paediatric age group. We describe the case of a male adolescent with recurrent erythema multiforme caused by herpes virus and transient natural killer deficiency.