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Background and Aims: Inflammation may influence the cardio-metabolic profile which relates with the risk of chronic diseases. This study aimed to assess the inflammatory status by metabolic health (MH)/body mass index (BMI) category and to assess how inflammatory markers can predict the cardio-metabolic profile in European adolescents, considering BMI.Methods and Results: A total of 659 adolescents (295 boys) from a cross-sectional European study were included. Adolescents were classified by metabolic health based on age- and sex-specific cut-off points for glucose, blood pressure, triglycerides, high density cholesterol and BMI. C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin (IL-6), complement factors (C3, C4) and cell adhesion molecules were assessed.Results: Metabolically abnormal (MA) adolescents had higher values of C3 (p < 0.001) and C4 (p = 0.032) compared to those metabolically healthy (MHy). C3 concentrations significantly increased with the deterioration of the metabolic health and BMI (p < 0.001). Adolescents with higher values of CRP had higher probability of being in the overweight/obese-MH group than those allocated in other categories. Finally, high C3 and C4 concentrations increased the probability of having an unfavorable metabolic/BMI status.Conclusions: Metabolic/BMI status and inflammatory biomarkers are associated, being the CRP, C3 and C4 the most related inflammatory markers with this condition. C3 and C4 were associated with the cardio-metabolic health consistently. [ABSTRACT FROM AUTHOR]

The aim of this study was to expand knowledge about endocrine disorders in individuals with Cornelia de Lange syndrome (CdLS), a rare developmental genetic disorder with anomalies in multiple organs and systems. Hormone levels, clinical scores, anthropometric measurements, and molecular analysis were assessed in 24 individuals with CdLS. Hyperprolactinemia was the most common endocrine disorder. Three patients showed subclinical hypothyroidism. Concerning the gonadotropic axis, mildly delayed puberty was observed, as well as genital anomalies, such as cryptorchidism. Despite short stature, levels of insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 tended to be normal. Three prepubertal individuals without risk factors had higher than normal values for the homeostatic model assessment of insulin resistance (HOMA-IR) and for insulinemia, suggesting insulin resistance. Furthermore, two adults had elevated body mass indexes associated with HOMA-IR values over the cut-off values. CdLS may lead to dysregulation of the endocrine system, particularly in patients with high HOMA-IR values and insulinemia who are at risk of insulin resistance. Therefore, clinical follow-up with comprehensive hormonal assessment appears warranted in individuals with CdLS., (©Copyright 2024 by Turkish Society for Pediatric Endocrinology and Diabetes / The Journal of Clinical Research in Pediatric Endocrinology published by Galenos Publishing House.)

Cornelia de Lange syndrome (CdLS) is a rare congenital developmental disorder with multisystemic involvement. The clinical presentation is highly variable, but the classic phenotype, characterized by distinctive craniofacial features, pre- and postnatal growth retardation, extremity reduction defects, hirsutism and intellectual disability can be distinguished from the nonclassic phenotype, which is generally milder and more difficult to diagnose. In addition, the clinical features overlap with those of other neurodevelopmental disorders, so the use of consensus clinical criteria and artificial intelligence tools may be helpful in confirming the diagnosis. Pathogenic variants in NIPBL, which encodes a protein related to the cohesin complex, have been identified in more than 60% of patients, and pathogenic variants in other genes related to this complex in another 15%: SMC1A, SMC3, RAD21, and HDAC8. Technical advances in large-scale sequencing have allowed the description of additional genes (BRD4, ANKRD11, MAU2), but the lack of molecular diagnosis in 15% of individuals and the substantial clinical heterogeneity of the syndrome suggest that other genes and mechanisms may be involved. Although there is no curative treatment, there are symptomatic/palliative treatments that paediatricians should be aware of. The main medical complication in classic SCdL is gastro-esophageal reflux (GER), which should be treated early., (Copyright © 2024 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Early-life onset of high blood pressure is associated with the development of cardiovascular diseases in adulthood. In adolescents, limited evidence exists regarding the association between adherence to the Mediterranean Diet (MedDiet) and normal blood pressure (BP) levels, as well as its potential to modulate genetic predisposition to HTN. This study investigated the interaction between a MedDiet score and a recently developed HTN-genetic risk score (HTN-GRS) on blood pressure levels in a European adolescent cohort. The MedDiet score was derived from two non-consecutive 24-h dietary recalls and ranged from 0 (indicating low adherence) to 9 (indicating high adherence). Multiple linear regression models, adjusted for covariates, were employed to examine the relationship between the MedDiet score and BP z-scores and to assess the interaction effects between the MedDiet score and HTN-GRS on BP z-scores. MedDiet score showed a negative association with z-systolic BP (SBP) (ß = -0.40, p < 0.001) and z-diastolic BP (DBP) (ß = -0.29, p = 0.001). Additionally, a significant interaction effect was identified between the MedDiet score and HTN-GRS on z-SBP (ß = 0.02, p < 0.001) and z-DBP (ß = 0.02, p < 0.001). The modulatory effect of the MedDiet was more pronounced in females than in males, and HTN-GRS exhibited a stronger influence on DBP than on SBP.   Conclusion: The study suggests that higher adherence to the MedDiet is associated with reduced BP levels in adolescents and provides evidence of a genetic-diet interaction influencing BP in adolescents. What is Known: • Adherence to the Mediterranean diet may reduce BP levels. What is New: • It is the first study to assess the connection between adherence to a Mediterranean diet, a hypertension genetic risk score, and how they interact in influencing blood pressure. • It is conducted within a multicenter cohort of European adolescents., (© 2024. The Author(s).)

Introduction: From genome wide association study (GWAS) a large number of single nucleotide polymorphisms (SNPs) have previously been associated with blood pressure (BP) levels. A combination of SNPs, forming a genetic risk score (GRS) could be considered as a useful genetic tool to identify individuals at risk of developing hypertension from early stages in life. Therefore, the aim of our study was to build a GRS being able to predict the genetic predisposition to hypertension (HTN) in European adolescents., Methods: Data were extracted from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) cross-sectional study. A total of 869 adolescents (53% female), aged 12.5-17.5, with complete genetic and BP information were included. The sample was divided into altered (≥130 mmHg for systolic and/or ≥80 mmHg for diastolic) or normal BP. Based on the literature, a total of 1.534 SNPs from 57 candidate genes related with BP were selected from the HELENA GWAS database., Results: From 1,534 SNPs available, An initial screening of SNPs univariately associated with HTN ( p  < 0.10) was established, to finally obtain a number of 16 SNPs significantly associated with HTN ( p  < 0.05) in the multivariate model. The unweighted GRS (uGRS) and weighted GRS (wGRS) were estimated. To validate the GRSs, the area under the curve (AUC) was explored using ten-fold internal cross-validation for uGRS (0.802) and wGRS (0.777). Further covariates of interest were added to the analyses, obtaining a higher predictive ability (AUC values of uGRS: 0.879; wGRS: 0.881 for BMI z -score). Furthermore, the differences between AUCs obtained with and without the addition of covariates were statistically significant ( p  <   0.05)., Conclusions: Both GRSs, the uGRS and wGRS, could be useful to evaluate the predisposition to hypertension in European adolescents., 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., (© 2023 Pérez-Gimeno, Seral-Cortes, Sabroso-Lasa, Esteban, Lurbe, Béghin, Gottrand, Meirhaeghe, Muntaner, Kafatos, Molnár, Leclercq, Widhalm, Kersting, Nova, Salazar-Tortosa, Gonzalez-Gross, Breidenassel, Sinningen, De Ruyter, Labayen, Rupérez, Bueno-Lozano and Moreno.)

This study assesses a possible cardiac dysfunction in individuals with Cornelia de Lange syndrome (CdLS) without diagnosed congenital heart disease (CHD) and its association with other factors. Twenty patients and 20 controls were included in the study divided into three age-dependent groups (A: < 10 yrs, B: 10-20 yrs, C: > 20 yrs), and were evaluated using conventional echocardiography, tissue doppler imaging (TDI), two-dimensional speckle tracking and genetic and biochemical analyses. The left ventricular global longitudinal strain (GLS) was altered (< 15.9%) in 55% of patients, being pathological in the older group (A: 19.7 ± 6.6; B: -17.2 ± 4.7; C: -13.6 ± 2.9). The speckle tracking technique revealed a downward trend in the values of strain, strain rate and velocity, especially in the oldest group. Likewise, the ejection fraction (LVEF) and shortening fraction (LVFS) values, although preserved, also showed a decreased with age (p < 0.05). The analytical markers of cardiovascular risk and cardiac function showed no alterations. The molecular analyses revealed 16 individuals carrying pathogenic variants in NIPBL, two with variants in SMC1A, one with a variant in RAD21 and one with a HDAC8 variant. This is the first systematic approach that demonstrates that individuals with CdLS may present early cardiomyopathy, which can be detected by speckle tracking technique even before the appearance of clinical symptoms and the alteration of other echocardiographic or analytical parameters. For all these reasons, cardiological followup is suggested even in the absence of CHD, especially from adolescence onwards., (© 2022. The Author(s).)

The Schuurs−Hoeijmakers syndrome (SHMS) or PACS1 Neurodevelopment Disorder (PACS1-NDD) is a rare autosomal dominant disease caused by mutations in the PACS1 gene. To date, only 87 patients have been reported and, surprisingly, most of them carry the same variant (c.607C>T; p.R203W). The most relevant clinical features of the syndrome include neurodevelopment delay, seizures or a recognizable facial phenotype. Moreover, some of these characteristics overlap with other syndromes, such as the PACS2 or Wdr37 syndromes. The encoded protein phosphofurin acid cluster sorting 1 (PACS-1) is able to bind to different client proteins and direct them to their subcellular final locations. Therefore, although its main function is protein trafficking, it could perform other roles related to its client proteins. In patients with PACS1-NDD, a gain-of-function or a dominant negative mechanism for the mutated protein has been suggested. This, together with the fact that most of the patients carry the same genetic variant, makes it a good candidate for novel therapeutic approaches directed to decreasing the toxic effect of the mutated protein. Some of these strategies include the use of antisense oligonucleotides (ASOs) or targeting of its client proteins.

Due to the absence of easily applicable cut-off points to determine high blood pressure or hypertension in children, as in the adult population, blood pressure is rarely measured in the pediatrician's clinical routine. This has led to an underdiagnosis of high blood pressure or hypertension in children. For this reason, the present study evaluate the utility of five equations for the screening of high blood pressure in children: blood pressure to height ratio, modified blood pressure to height ratio, new modified blood pressure to height ratio, new simple formula and height-based equations. The authors evaluated 1599 children between 5 and 18 years. The performance of the five equations was analyzed using the receiver-operating characteristics curves for identifying blood pressure above P90th according to the American Academy of Pediatrics Clinical Practice Guideline 2017. All equations showed an area under the curve above 0.882. The new modified blood pressure to height ratio revealed a high sensitivity whereas the height-based equations showed the best performance, with a positive predictive value above 88.2%. Finally, all equations showed higher positive predictive values in children with overweight or obesity. The height-based equation obtained the highest PPV values above 71.1% in children with normal weight and above 90.2% in children with overweight or obesity. In conclusions, the authors recommend the use of the height-based equations equation because it showed the best positive predictive values to identify children with elevated blood pressure, independently of their sex, pubertal and weight status., (© 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Introduction: Eating behavior is often established during the first years of life. Therefore, it is important to make a research on it to understand the relationships that children have with food and how this can contribute to prevent the development of childhood obesity. An appropriate assessment of eating behavior can be achieved using the "Child Eating Behavior Questionnaire" (CEBQ). This questionnaire has been validated in several populations and languages, but it has never been translated, adapted, and validated for Spanish children., Aim: To evaluate the reliability and internal consistency of the CEBQ questionnaire, culturally adapted and translated into Spanish (Spain), in Spanish families with children aged 3 to 6 years, as well as its association with children's body mass index (BMI) to test its construct validity., Materials and Methods: Children between 3 and 6 years old were recruited from the ongoing MELI-POP randomized controlled clinical trial, as well as from public schools located in middle class neighborhoods of Zaragoza, Spain, to complete the sample. Sociodemographic characteristics and anthropometric measures were obtained according to standardized methods. The 35-item CEBQ questionnaire was completed twice with a time difference of 3 weeks between each response. Statistical analyses included the evaluation of internal consistency and reliability of the questionnaire, a confirmatory factor analysis, and the association between the different CEBQ scales and the children's BMI., Results: A total of 197 children completed variables; 97 of them were boys (49.2%) and 100 girls (50.8%). Mean age of the total sample was 4.7 ± 0.9 years. There was a high test-re-test reliability of the questionnaire with values close to 1, with an average of 0.66 and a good internal consistency (Cronbach alpha with values above 0.7), so that a high reliability is established between the items in each scale. A gradual positive association was found between the score of different "pro-intake" scales of the CEBQ: "Food Responsiveness," "Emotional Overeating," and "Enjoyment of food" and the children's BMI; at the opposite, negative associations were observed between BMI and the score of anti-intake scales "Satiety Responsiveness," "Slowness in Eating," and "Emotional Undereating.", Conclusion: The Spanish version of the CEBQ is a useful tool to assess the eating behavior of Spanish children because the high reliability and internal validity. There is a significant association between eating behavior and BMI in Spanish children., Competing Interests: JS-S is a non-paid member of the Scientific Committee of the International Nut and Dried Fruit Foundation. He has received grants/research support from the American Pistachio Growers and International Nut and Dried Fruit Foundation through his Institution. He is an honorary member of the “Instituto Danone” in Spain and non-paid member of International Danone Institute. The remaining 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., (Copyright © 2022 Jimeno-Martínez, Maneschy, Moreno, Bueno-Lozano, De Miguel-Etayo, Flores-Rojas, Jurado-Castro, de Lamas, Vázquez-Cobela, Martinez-Lacruz, Portoles, Martínez, Navas-Carretero, Schröder, Fitó, Babio, Salas-Salvadó, Leis, Gil-Campos and Rupérez.)

Childhood obesity has been related to metabolic syndrome and low-grade chronic inflammation. This study aimed to evaluate the impact of physical activity intensities and practice on inflammation, endothelial damage, and cardiometabolic risk factors in children. There were 513 participants, aged 6-14 years, recruited for the study. Physical activity was measured by accelerometry, and the children were classified into four groups according to quartiles of moderate to vigorous physical activity (MVPA) practice as very low active, low active, moderate active, and high active. Anthropometric measures, blood pressure, and plasma metabolic and proinflammatory parameters were analyzed. Very low active group presented a worse lipid profile and higher insulin, leptin, adiponectin, resistin, matrix metallopeptidase-9, and tissue plasminogen activator inhibitor-1, while lower levels of tumor necrosis factor-alpha, Type 1 macrophages, and interleukin 8 than high-active children. Regression analyses showed that a higher MVPA practice was associated with lower levels of triacylglycerols (β: -0.118; p = .008), resistin (β: -0.151; p = .005), tPAI (β: -0.105; p = .046), and P-selectin (β: -0.160; p = .006), independently of sex, age, and body mass index (BMI). In contrast, a higher BMI was associated with higher levels of insulin (β: 0.370; p < .001), Homeostasis Model Assessment (β: 0.352; p < .001), triacylglycerols (β: 0.209; p < .001), leptin (β: 0.654; p < .001), tumor necrosis factor-alpha (β: 0.182; p < .001), Type 1macrophages (β: 0.181; p < .001), and tissue plasminogen activator inhibitor (β: 0.240; p < .001), independently of sex, age, and MVPA. A better anthropometric, metabolic, and inflammatory profile was detected in the most active children; however, these differences were partly due to BMI. These results suggest that a higher MVPA practice and a lower BMI in children may lead to a better cardiometabolic status.

Disturbances in eating behaviors have been widely related to obesity. However, little is known about the role of obesity-related biomarkers in shaping habitual patterns of eating behaviors (i.e., eating styles) in childhood. The objective of the present study was to explore the relationships between several biomarkers crucially involved in obesity (ghrelin, insulin resistance, and leptin/adiponectin ratio) and eating styles in children and adolescents with obesity. Seventy participants aged between 8 and 16 (56.2% men) fulfilled the Spanish version of the Dutch Eating Behavior Questionnaire for Children to measure external, emotional, and restrained eating styles. In addition, concentrations of ghrelin, leptin, adiponectin, insulin, and glucose were obtained through a blood test. Hierarchical multiple regression analyses controlling for age and sex were computed for each eating style. Results indicated that individuals with higher ghrelin concentration levels showed lower scores in restrained eating (β = -0.61, p < 0.001). The total model explained 32% of the variance of the restrained pattern. No other relationships between obesity-related biomarkers and eating behaviors were found. This study highlights that one of the obesity-risk factors, namely lower plasma ghrelin levels, is substantially involved in a well-known maladaptive eating style, restraint eating, in childhood obesity.

Tenorio syndrome (TNORS) (OMIM #616260) is a relatively recent disorder with very few cases described so far. Clinical features included macrocephaly, intellectual disability, hypotonia, enlarged ventricles and autoimmune diseases. Molecular underlying mechanism demonstrated missense variants and a large deletion encompassing RNF125, a gene that encodes for an U3 ubiquitin ligase protein. Since the initial description of the disorder in six patients from four families, several new patients were diagnosed, adding more evidence to the clinical spectrum. In this article, we described 14 additional cases with deep phenotyping and make an overall review of all the cases with pathogenic variants in RNF125. Not all patients presented with overgrowth, but instead, most patients showed a common pattern of neurodevelopmental disease, macrocephaly and/or large forehead. Segregation analysis showed that, though the variant was inherited in some patients from an apparently asymptomatic parent, deep phenotyping suggested a mild form of the disease in some of them. The mechanism underlying the development of this disease is not well understood yet and the report of further cases will help to a better understanding and clinical characterization of the syndrome., (© 2021 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Postzygotic mosaicism (PZM) in NIPBL is a strong source of causality for Cornelia de Lange syndrome (CdLS) that can have major clinical implications. Here, we further delineate the role of somatic mosaicism in CdLS by describing a series of 11 unreported patients with mosaic disease-causing variants in NIPBL and performing a retrospective cohort study from a Spanish CdLS diagnostic center. By reviewing the literature and combining our findings with previously published data, we demonstrate a negative selection against somatic deleterious NIPBL variants in blood. Furthermore, the analysis of all reported cases indicates an unusual high prevalence of mosaicism in CdLS, occurring in 13.1% of patients with a positive molecular diagnosis. It is worth noting that most of the affected individuals with mosaicism have a clinical phenotype at least as severe as those with constitutive pathogenic variants. However, the type of genetic change does not vary between germline and somatic events and, even in the presence of mosaicism, missense substitutions are located preferentially within the HEAT repeat domain of NIPBL. In conclusion, the high prevalence of mosaicism in CdLS as well as the disparity in tissue distribution provide a novel orientation for the clinical management and genetic counselling of families., (© 2021. The Author(s).)

Longitudinal changes of physical activity (PA) from childhood into adolescence have not been accurately described yet for the Spanish population. The aim of this study is to evaluate the changes of PA, assessed by accelerometry and anthropometric measures in a cohort of 213 children from the prepubertal to pubertal period, focusing on those with valid data from both time points ( n = 75). Sedentary time (ST) increased about 50%, while all PA intensities declined from the pre-pubertal to pubertal period. Light PA (LPA) was the major contributor, decreasing by about 30%. Boys were more active than girls in both periods, but they showed a higher decline in PA, especially moderate-to-vigorous PA (MVPA). The proportion who reached the recommendation of 60 min of MVPA decreased by 33.3% in boys and 4.6% in girls. Children with obesity or overweight had lower MVPA than those with normal-weight in the pre-pubertal period, but no differences were found in the pubertal period. This study shows a decrease of PA and an increase of sedentarism in the transition from childhood to adolescence, particularly in boys. Regardless of body weight, adolescents tend to be less active. Therefore, prevention programs should be implemented to achieve optimal PA and reduce sedentarism during infancy considering the differences found by sex., Competing Interests: The authors declare no conflict of interest. The sponsors had no role in the design, execution, interpretation, or writing of the study.

High blood pressure (BP) is a risk factor for cardiovascular disease and sodium consumption is related to high BP. Moreover, sugar-sweetened beverages (SSB) and the Dietary Approach to Stop Hypertension (DASH) influence BP. For this reason, we investigated whether: 1) children with risk of elevated BP had a higher consumption frequency (CF) of energy-dense salty foods (EDSF), high-sugary foods (HSF) and SSB or a low DASH score; and 2) children with a higher CF of EDSF showed a worse anthropometric and metabolic profile. Anthropometry, BP and general biochemical parameters were measured in 687 Spanish children (5-16 years) with normal or excess weight. A food frequency questionnaire was used to calculate EDSF, HSF and SSB consumption, and modified DASH score. Results showed that sex and pubertal stage influenced modified DASH score. Diastolic hypertension was associated to higher CF of EDSF in the whole sample and to higher CF of SSB in pubertal children, both independently of nutritional status. In addition, CF of EDSF was positively associated with CF of HSF and SSB and inversely associated with modified DASH score. Targeted policies and intervention programs, specific for different age ranges, should be established that aim to reduce salt consumption from snacks and processed foods, which could reduce HSF and SSB consumption as well.

Characteristic or classic phenotype of Cornelia de Lange syndrome (CdLS) is associated with a recognisable facial pattern. However, the heterogeneity in causal genes and the presence of overlapping syndromes have made it increasingly difficult to diagnose only by clinical features. DeepGestalt technology, and its app Face2Gene, is having a growing impact on the diagnosis and management of genetic diseases by analysing the features of affected individuals. Here, we performed a phenotypic study on a cohort of 49 individuals harbouring causative variants in known CdLS genes in order to evaluate Face2Gene utility and sensitivity in the clinical diagnosis of CdLS. Based on the profile images of patients, a diagnosis of CdLS was within the top five predicted syndromes for 97.9% of our cases and even listed as first prediction for 83.7%. The age of patients did not seem to affect the prediction accuracy, whereas our results indicate a correlation between the clinical score and affected genes. Furthermore, each gene presents a different pattern recognition that may be used to develop new neural networks with the goal of separating different genetic subtypes in CdLS. Overall, we conclude that computer-assisted image analysis based on deep learning could support the clinical diagnosis of CdLS., Competing Interests: The authors declare no conflicts of interest.

There are three human enzymes with HMG-CoA lyase activity that are able to synthesize ketone bodies in different subcellular compartments. The mitochondrial HMG-CoA lyase was the first to be described, and catalyzes the cleavage of 3-hydroxy-3-methylglutaryl CoA to acetoacetate and acetyl-CoA, the common final step in ketogenesis and leucine catabolism. This protein is mainly expressed in the liver and its function is metabolic, since it produces ketone bodies as energetic fuels when glucose levels are low. Another isoform is encoded by the same gene for the mitochondrial HMG-CoA lyase ( HMGCL ), but it is located in peroxisomes. The last HMG-CoA lyase to be described is encoded by a different gene, HMGCLL1, and is located in the cytosolic side of the endoplasmic reticulum membrane. Some activity assays and tissue distribution of this enzyme have shown the brain and lung as key tissues for studying its function. Although the roles of the peroxisomal and cytosolic HMG-CoA lyases remain unknown, recent studies highlight the role of ketone bodies in metabolic remodeling, homeostasis, and signaling, providing new insights into the molecular and cellular function of these enzymes.

Introduction: Premature pubarche (PP) is generally thought to be a benign condition, but it can also be the first sign of underlying disease., Objective: To analyse the aetiology and the evolution of the anthropometric, analytical and metabolic risk parameters of a group of patients with PP., Material and Methods: A descriptive and analytical retrospective study of 92 patients affected by PP. Anthropometry, analyses, bone age and indicators of lipid metabolism were all evaluated., Results: The sample included 92 patients with PP (67 female and 25 male), with a mean age of 7.1±0.6 for girls and 8.3±0.7 for boys. Small for gestational age was recorded in 7.7%. There was an accelerated bone age (1.20±0.1 years). A total of 21 patients were classified as idiopathic (23%), 60 as idiopathic premature adrenarche (65%), and 11 with non-classic congenital adrenal hyperplasia (12%). Puberty was reached early (11+0.9 years old in boys and 9.9±0.8 in girls), as was menstruation age (11.8+1.1 years old), P<.001. The stature finally reached was close to their genetic stature. There is a positive correlation between body mass index, blood glucose and LDL cholesterol, as well as a tendency towards hyperinsulinaemia., Conclusions: The present study shows that PP is a benign condition in the majority of cases, but non-classic congenital adrenal hyperplasia (12%) is not uncommon. Menstruation and puberty started early and bone age was accelerated. Growth was normal, and more or less in line with genetic size. PP associated with obesity is linked with analytical variations of metabolic risks., (Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Childhood obesity is a high prevalence health problem. Although there are clinical guidelines for its management, there is variability in its clinical approach. The aim of this study is to describe the usual clinical practice in Paediatric Endocrinology Units in Spain and to evaluate if it resembles the recommended guidelines., Material and Methods: An observational, cross-sectional and descriptive study was carried out by means of a questionnaire sent to paediatric endocrinologists of the Spanish Society of Paediatric Endocrinology. The questions were formulated based on the recommendations of "Clinical Practice Guidelines on the Prevention and Treatment of Childhood Obesity" issued by the Spanish Ministry of Health., Results: A total of 125 completed questionnaires were obtained from all Autonomous Communities. Variability was observed both in the number of patients attended and in the frequency of the visits. The majority (70%) of the paediatricians who responded did not have a dietitian, psychologist or psychiatrist, in their centre to share the treatment for obese children. As regards treatment, dietary advice is the most used, and 69% have never prescribed weight-loss drugs. Of those who have prescribed them, 52.6% did not use informed consent as a prior step to them being used., Conclusions: There are few centres that comply with the recommendations of the clinical practice guidelines on prevention and treatment of childhood obesity as an established quality plan. Clinical practice differs widely among the paediatric endocrinologists surveyed. There are no uniform protocols of action, and in general there is limited availability of resources for the multidisciplinary treatment required by this condition., (Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction and Objectives: Small for gestational age (SGA) children without catch-up growth can benefit from treatment with growth hormone (rhGH). However, they should be monitored very closely because they are at increased risk of metabolic syndrome., Material and Method: A group of 28 SGA children with a mean age of 8.79 years and undergoing treatment with rhGH were selected for evaluation. Over the course of 4 years, an annual evaluation was performed on the anthropometric variables (weight, height, body mass index [BMI], growth rate, blood pressure and waist perimeter), metabolic risk variables (glycaemia, glycosylated haemoglobin, cholesterol ratio, insulinaemia, insulin-like growth factor 1[IGF1], IGF binding protein-3 [IGFBP-3], IGF1/IGFBP3 ratio, and HOMA index), and body composition variables., Results: Treatment with rhGH was associated with a significant increase in height (-2.76±.11 SD to -1.53±.17 SD, P=.000), weight (-1.50±.09 SD to -1.21±.13 SD; P=.016), and growth rate (-1.43±.35 SD to .41±.41 SD; P=.009), without a corresponding change in the BMI. Insulinaemia (9.33±1.93mU/ml to 16.55±1.72mU/ml; P=.044) and the HOMA index (3.63±.76 to 6.43±.67; P=.042) increased, approaching insulin resistance levels. No changes were observed in the lipid profile. Body composition changes were observed, with a significant increase in lean mass (73.19±1.26 to 78.74±1.31; P=.037), and a reduction of fat mass (26.81±1.26 to 21.26±1.31; P=.021)., Conclusion: Treatment with rhGH is effective for improving anthropometric variables in SGA patients who have not experienced a catch-up growth. It also produces changes in body composition, which may lead to a reduction in risk of metabolic syndrome. However, some insulin resistance was observed. It is important to follow up this patient group in order to find out whether these changes persist into adulthood., (Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction and Objectives: Small for gestational age (SGA) patients have an increased risk of developing a cardiovascular pathology, as well as a metabolic syndrome. Our objective is to evaluate the cardiac morphology and function of SGA children treated with growth hormone (GH), identifying changes that could potentially have long-term consequences., Methods: We selected 23 SGA school-age patients and 23 healthy children. We measured their weight, height, blood pressure and heart rate. Using transthoracic echocardiography, we evaluated cardiac chamber size, ascending and abdominal aortic diameter as well as the systolic and diastolic function of both ventricles., Results: SGA children have a higher systolic and diastolic blood pressure (P<.05) without significant changes in their heart rate. They also have a thicker interventricular septum (SGA Z-score 1.57 vs. 0.89; P=.026) and a worse right ventricular systolic function, with a lower TAPSE (SGA Z-score -0.98 vs. 0.95; P=.000), as well as a lower blood flow rate in the pulmonary artery (SGA 0.85m/s vs. 0.97m/s; P=.045). No significant difference was observed in the patients' left ventricular function. SGA patients' ascending aortic diameter was greater (SGA Z-score -1.09 vs. -1.93; P=.026), whereas the systolic abdominal aortic diameter was smaller (SGA Z-score-0.89 vs. -0.19; P=.015)., Conclusions: We found functional and morphological cardiac changes in SGA school-age patients treated with GH. It is important to follow-up this patient group in order to determine if these changes contribute to an increased cardiac morbidity in adulthood., (Copyright © 2016 Elsevier España, S.L.U. All rights reserved.)

Background and Objectives: Small for gestational age (SGA) children are at increased risk of metabolic syndrome. Our objective is to evaluate changes in body composition produced by growth hormone (GH) treatment., Patients and Method: A group of 28 SGA children without catch-up growth and undergoing treatment with GH was selected for evaluation. Over the course of 3 years from the beginning of the treatment with GH, the children's body composition variables (bone mineral density [BMD], fat and lean body mass proportion) were evaluated annually with dual-energy X-ray absorptiometry. A study of correlation between metabolic and body composition variables was also made., Results: Treatment with GH produces a reduction in fat mass proportion in relation to lean body mass, decreasing from 25.94±6.09 to 22.88±5.38% (P=.034). In the abdominal regions we observe an increase in lean mass, from 1,356,91±426,71 to 2,570,96±814,36g (P=.000) and a tendency for visceral fat deposits to decrease. BMD in lumbar vertebrae improved from -1.55±0.68 to -0.90±0.79Z (P=.019)., Conclusions: Treatment with GH produces changes in body composition, improving BMD and increasing the proportion of lean body mass with a reduction in fat mass. If these changes persisted into adulthood, they may cause a reduction in the metabolic and cardiovascular risk in this group of patients., (Copyright © 2016 Elsevier España, S.L.U. All rights reserved.)

For years now, a stronger tendency towards overweight among diabetes 1 population has been described, a tendency already observed during childhood and pubescence. Insulin replacement therapy to be one of the main underlying factors. Clarifying these issues and determining whether this weight gain may bring in an increased cardiovascular risk in these patients during their adulthood is critical in order to develop strategies that prevent or at least diminish this evolution. This review aims at updating the anthropometric status and the presence of excess body fat in children and adolescents with type 1 diabetes as compared to healthy population, establishing the relevance of the different factors implied and their potential effect on cardiovascular risk., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

Cornelia de Lange Syndrome (CdLS) is a congenital autosomal dominant (NIPBL, SMC3 and RAD21) or X-linked (SMC1A and HDAC8) disorder characterized by facial dysmorphism, pre and postnatal growth retardation, developmental delay and/or intellectual disability, and multiorgan involvement. Musculoskeletal malformations are usually bilateral and affect mainly the upper limbs; the range goes from brachyclinodactyly to severe reduction defects. Instead lower extremities are usually less and mildly involved. Here, we report on a 3-year-old Senegalese boy with typical craniofacial CdLS features, pre and postnatal growth retardation, atrial septal defect, developmental delay and right ipsilateral limb malformations, consistent with oligodactyly of the 3rd and 4th fingers, tibial agenesis and fibula hypoplasia. Exome sequencing and Sanger sequencing showed a novel missense mutation in NIPBL gene (c.6647A>G; p.(Tyr2216Cys)), which affects a conserved residue located within NIPBL HEAT repeat elements. Pyrosequencing analysis of NIPBL gene, disclosed similar levels of wild-type and mutated alleles in DNA and RNA samples from all tissues analyzed (oral mucosa epithelial cells, peripheral blood leukocytes and fibroblasts). These findings indicated the absence of somatic mosaicism, despite of the segmental asymmetry of the limbs, and confirmed biallelic expression for NIPBL transcripts, respectively. Additionally, conditions like Split-hand/foot malformation with long-bone deficiency secondary to duplication of BHLHA9 gene have been ruled out by the array-CGH and MLPA analysis. To our knowledge, this is the first CdLS patient described with major ipsilateral malformations of both the upper and lower extremities, that even though this finding could be due to a random event, expands the spectrum of limb reduction defects in CdLS., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)