Association among nocturnal enuresis, body weight and obstructive sleep apnea in children of south Italy: an observational study.

BACKGROUND: To evaluate the rate of nocturnal enuresis (NE), body weight and obstructive sleep apnea in children 5 to 10 years of age in South Italy and the possible association among these disorders. METHODS: We have administered 1100 validated questionnaires, in Italian language, to parents and we have analyzed data with a logistic regression. RESULTS: Forty-two percent of children had a BMI≥85th (group 1) vs 58.0% normal weight children at the same age (group 2). There is a higher number of overweight males compared to females without statistically differences. In group 1 there was a higher number of children with NE and obstructive sleep disorders and some children present with the association among these three disorders. CONCLUSIONS: There are no statistically differences between two study groups for the association body weight-NE, body weight-NE-obstructive sleep disorders.

Osteoporosis in childhood.

PURPOSE OF REVIEW: The aim of this review is to highlight recent findings in prevention, diagnosis, and treatment of pediatric osteoporosis. RECENT FINDINGS: Several genes are involved in bone mass acquisition, and various monogenic bone disorders characterized by reduced bone mineral density and increased bone fragility have been recently described. Moreover, many chronic diseases and/or their treatment have been associated with impaired bone mass acquisition. Pediatric osteoporosis should be adequately suspected and properly diagnosed in children at risk of fractures. Particularly, detection of vertebral fracture allows the diagnosis regardless of densitometric evaluation. Dual X-ray absorptiometry remains the most widely used densitometric technique in childhood, but interpretation of results should be made with caution because of different confounding factors. Bisphosphonates represent one of the main medical treatments of pediatric osteoporosis, and many different protocols have been proposed. Bisphosphonates administration should be characterized by a first phase, followed by a period of maintenance. Optimal route of administration, duration of therapy, and long-term safety of bisphosphonates treatment require further investigation. SUMMARY: Careful monitoring of children at risk of fractures is essential to pose early diagnosis of osteoporosis. In children with persistent risk factors and reduced probability of spontaneous recovery, medical treatment with bisphosphonates should be considered.

A 6.5 mb deletion at 3q24q25.2 narrows Wisconsin syndrome critical region to a 750 kb interval: A potential role for MBNLI.

We report on a patient with a 6.5 Mb interstitial de novo deletion in 3q24q25.2, characterized by array CGH. The patient is a 4-year and 2-month-old girl, who presented to us with mild developmental delay, absence of language, facial dysmorphism, hirsutism, strabismus, and Dandy-Walker Malformation. The main clinical signs typical of WS (Wisconsin syndrome) are evident in the patient. The molecular mapping of WS in 3q23q25 allowed geneticists to define the syndrome more accurately. Comparing the present patient's phenotype with that of cases with a molecular characterization so far reported, it was possible to narrow the critical region for WS to an interval of 750 Kb, where two genes (MBNL1 and TMEM14E) are harbored. The potential role of MBNL1 in causing the WS phenotype is discussed. © 2016 Wiley Periodicals, Inc.

DSM-5 criteria for PTSD in parents of pediatric patients with epilepsy: What are the changes with respect to DSM-IV-TR?

Increasing literature suggests the need to explore for post-traumatic stress disorder (PTSD) and post-traumatic stress symptoms in parents and caregivers of children with acute and chronic illnesses but scant data are available on epilepsy. The aim of the present study was to estimate full and partial PTSD rates among parents of children with epilepsy comparing DSM-5 and DSM-IV-TR criteria. Further, the aim of the present study was to examine possible gender differences between mothers and fathers. Results showed 9.1% and 12.1% PTSD rates in the total sample, according to DSM-5 or DSM-IV-TR criteria, respectively, with an overall consistency of 92.9% (Kohen's K=0.628, p=.453). Significant gender differences emerged for Avoidance/Numbing and Hyperarousal symptoms diagnosed by means of DSM-IV-TR criteria, as well as for Negative alterations in cognitions/mood and Hyperarousal symptoms, when adopting DSM-5 criteria. This study underscores the relevance of detecting PTSD in parents of children with a chronic illness such as epilepsy.

Gene editing of DNAH11 restores normal cilia motility in primary ciliary dyskinesia.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare autosomal recessive genetic disorder characterised by dysfunction of motile cilia. Ciliary dysmotility causes poor mucociliary clearance and leads to impairment of pulmonary function and severe respiratory infections. PCD has no specific therapy. With the aim to permanently restore gene function and normalise ciliary motility, we used gene editing to replace mutated with wild-type sequence in defective cells. METHODS: The target gene was dynein heavy chain 11 (DNAH11), an essential component of ciliary structure. Airway ciliated cells were collected from two patients with PCD with DNAH11 nonsense mutations and altered ciliary beating and pattern. Repair of the genetic defect was performed ex vivo by site-specific recombination using transcription activator-like effector nucleases (TALENs). RESULTS: In an epithelial cell line engineered to contain the DNAH11 target site, TALENs cleaved over 80% of the mutated DNAH11 sequence and replaced the mutated sequence with wild-type sequence in about 50% of cells. In airway ciliated cells of patients with PCD, site-specific recombination and normalisation of ciliary beating and pattern occurred in 33% and 29% of cells, respectively. CONCLUSION: This study demonstrates that gene editing can rescue ciliary beating ex vivo, opening up new avenues for treating PCD.

Vitamin D in childhood and adolescence: an expert position statement.

UNLABELLED: Vitamin D is a key hormone in the regulation of calcium and phosphorus metabolism and plays a pivotal role in bone health, particularly during pediatric age when nutritional rickets and impaired bone mass acquisition may occur. Great interest has been placed in recent years on vitamin D's extraskeletal actions. However, while recent data suggest a possible role of vitamin D in the pathogenesis of several pathological conditions, including infectious and autoimmune diseases, the actual impact of vitamin D status on the global health of children and adolescents, other than bone, remains a subject of debate. In the meantime, pediatricians still need to evaluate the determinants of vitamin D status and consider vitamin D supplementation in children and adolescents at risk of deficiency. This review is the result of an expert meeting that was held during the congress "Update on vitamin D and bone disease in childhood" convened in Pisa, Italy, in May 2013. CONCLUSION: The collaboration of the international group of experts produced this "state of the art" review on vitamin D in childhood and adolescence. After dealing with vitamin D status and its determinants, the review outlines the current debate on vitamin D's health benefits, concluding with a practical approach to vitamin D supplementation during childhood and adolescence. WHAT IS KNOWN: • Vitamin D deficiency is a worldwide health problem. • Vitamin D deficiency affects not only musculoskeletal health but also a potentially wide range of acute and chronic diseases. What is New: • We reviewed the literature focusing on randomized controlled trials of vitamin D supplementation during childhood and adolescence. • This review will help pediatricians to appreciate the clinical relevance of an adequate vitamin D status and it will provide a practical approach to vitamin D supplementation.

Vitamin D status and predictors of hypovitaminosis D in Italian children and adolescents: a cross-sectional study.

UNLABELLED: Hypovitaminosis D affects children and adolescents all around the world. Italian data on vitamin D status and risk factors for hypovitaminosis D during pediatric age are lacking. Six hundred fifty-two children and adolescents (range 2.0-21.0 years) living in the northwestern area of Tuscany were recruited at the Department of Pediatrics, University Hospital Pisa. None of them had received vitamin D supplementation in the previous 12 months. 25-hydroxyvitamin D (25-OH-D) and parathyroid hormone (PTH) levels were analyzed in all subjects. Severe vitamin D deficiency was defined as serum levels of 25-OH-D<25.0 nmol/L (10.0 ng/mL) and vitamin D deficiency a<50.0 nmol/L (20.0 ng/mL). Serum 25-OH-D levels of 50.0-74.9 nmol/L (20.0-29.9 ng/mL) indicated vitamin D insufficiency, whereas 25-OH-D levels ≥ 75.0 nmol/L (30.0 ng/mL) were considered sufficient. Hypovitaminosis D was defined as 25-OH-D levels<75.0 nmol/L (30.0 ng/mL). The median serum 25-OH-D level was 51.8 nmol/L, range 6.7-174.7 (20.7 ng/mL, range 2.7-70.0), with a prevalence of vitamin D deficiency, insufficiency, and sufficiency of 45.9, 33.6, and 20.5 %, respectively. The prevalence of severe vitamin D deficiency was 9.5 %. Adolescents had lower median 25-OH-D levels (49.8 nmol/L, range 8.1-174.7; 20.0 ng/mL, range 3.2-70.0) than children (55.6 nmol/L, range 6.8-154.6; 22.3 ng/mL, range 2.7-61.9, p=0.006). Non-white individuals (n=37) had median serum 25-OH-D levels in the range of deficiency (28.2 nmol/L, range 8.1-86.2; 11.3 ng/mL, range 3.2-34.5), with 36/37 having hypovitaminosis D. Logistic regression showed significant increased risk of hypovitaminosis D in the following: blood samples taken in winter (odds ratio (OR) 27.20), spring (OR 26.44), and fall (OR 8.27) compared to summer; overweight (OR 5.02) and obese (OR 5.36) subjects compared to individuals with normal BMI; low sun exposure (OR 8.64) compared to good exposure, and regular use of sunscreens (OR 7.06) compared to non-regular use. Gender and place of residence were not associated with vitamin D status. The 25-OH-D levels were inversely related to the PTH levels (r=-0.395, p<0.0001). Sixty-three out of the 652 (9.7 %) subjects showed secondary hyperparathyroidism. CONCLUSION: Italian children and adolescents who were not receiving vitamin D supplementation had high prevalence of hypovitaminosis D. Careful identification of factors affecting vitamin D status is advisable to promptly start vitamin D supplementation in children and adolescents.

Nuclear damage in peripheral lymphocytes of obese and overweight Italian children as evaluated by the gamma-H2AX focus assay and micronucleus test.

Childhood obesity, often characterized by a chronic low-grade inflammation, has been associated with an increased risk of developing some types of cancer later in life. Nuclear γ-H2AX foci represent the first detectable response of cells to DNA tumorigenesis lesions, such as the double-strand breaks (DSBs). An excess of micronucleated peripheral lymphocytes was found in subjects with cancer or inflammation-based diseases. We set out to investigate the expression of genome damage, from DNA lesions to chromosome mutations (micronuclei), in overweight and obese children. Using the γ-H2AX focus assay and micronucleus (MN) test, we analyzed peripheral lymphocytes from 119 Italian children classified as normal weight (n=38), overweight (n=20), or obese (n=61). Cultures treated with bleomycin (BLM) were also set up for each child in both assays to check functioning of the apparatus that ensures DNA integrity. We measured serum TNF-α, IL-6, and C-reactive protein (CRP) as markers of inflammation. Overweight and obese children had significantly higher levels of H2AX phosphorylation (0.0191±0.0039 and 0.0274±0.0029 γ-H2AXF/n) and increased MN frequencies (2.30±0.25 and 2.45±0.22‰) than normal-weight children (0.0034±0.0006 γ-H2AXF/n, and 0.92±0.12‰ MN), while all subjects responded to BLM induction, irrespective of their weight status. The fold increase of spontaneous MN frequencies in overweight and obese subjects was 2.5 and 2.7, respectively, well below the corresponding increase in the γ-H2AX foci (5.6- and 8.0-fold, respectively). IL-6 and CRP mean values were significantly higher in obese and overweight children than in controls. Here, we demonstrated that peripheral cells of overweight and obese children showed increased levels of DSBs, which were not completely repaired as part of them has been converted into micronuclei. Characterization of childhood obesity inflammation could be implemented using molecular markers of genome damage.

Mycoestrogen pollution of Italian infant food.

OBJECTIVE: To determine the concentrations of zearalenone and its metabolites in the leading brands of infant formula milks and meat-based infant foods commonly marketed in Italy, and to assess their repercussion in the provisional tolerable daily intakes of these estrogenic mycotoxins. STUDY DESIGN: A total of 185 cow's milk-based infant formulas and 44 samples of meat-based infant foods samples were analyzed. The analysis of mycotoxins was performed by immunoaffinity column clean-up and high-pressure liquid chromatography with fluorescence detection. RESULTS: Zearalenone was detected in 17 (9%) milk samples (maximum 0.76 µg/L). The α-zearalenol was detected in 49 (26%) milk samples (maximum 12.91 µg/L). The ß-zearalenol was detected in 53 (28%) milk samples (maximum 73.24 µg/L). The α-zearalanol and ß-zearalanol were not detected in milk samples. Although α-zearalenol was detected in 12 (27%) meat samples (maximum 30.50 µg/kg), only one meat-based sample was contaminated by α-zearalanol (950 µg/kg). Zearalenone, ß-zearalenol, and ß-zearalanol were not detected in meat samples. CONCLUSIONS: This study shows the presence of mycoestrogens in infant (milk-based and meat-based) food, and this is likely to have great implications for subsequent generations, suggesting the need to perform occurrence surveys in this type of food.

Circulating endothelial progenitor cells and large artery structure and function in young subjects with uncomplicated type 1 diabetes.

BACKGROUND: Carotid intima-media thickness (IMT), indices of large artery stiffness and measures of endothelium function may be used as markers of early atherosclerosis in type 1 diabetes mellitus (T1DM). The aim of the present study was to compare the indices of large artery structure and function as well as endothelial function and regenerating capacity between adolescents with T1DM and healthy control of similar age. In addition, the associations of different vascular measures with endothelial progenitor cells (EPCs), glyco-metabolic control and serum levels of advanced glycation endproducts (AGEs), soluble receptors for AGEs (sRAGE) and adiponectin were evaluated. METHODS: Sixteen uncomplicated young T1DM patients (mean age 18 ± 2 years, history of disease 11 ± 5 years, HbA1c 7.7 ± 1.1%) and 26 controls (mean age 19 ± 2 years) were studied. A radiofrequency-based ultrasound system (Esaote MyLab 70) was used to measure carotid IMT and wave speed (WS, index of local stiffness), applanation tonometry (PulsePen) was applied to obtain central pulse pressure (PP) and augmentation index (AIx), and carotid-femoral pulse wave velocity (PWV, Complior) was used as index of aortic stiffness. Peripheral endothelium-dependent vasodilation was determined as reactive hyperemia index (RHI, EndoPAT). Circulating EPCs, glycometabolic profile, AGEs (autofluorescence method), sRAGE and adiponectin were also measured. RESULTS: After adjusting for age, sex and blood pressure, T1DM adolescents had significantly higher carotid IMT (456 ± 7 vs. 395 ± 63 µm, p < 0.005), carotid WS (p < 0.005), PWV (p = 0.01), AIx (p < 0.0001) and central PP (p < 0.01) and lower EPCs (p = 0.02) as compared to controls. RHI was reduced only in diabetic patients with HbA1c ≥7.5% (p < 0.05). In the overall population, EPCs were an independent determinant of carotid IMT (together with adiponectin), while fasting plasma glucose was an independent determinant of carotid WS, AIx and central PP. CONCLUSIONS: Our findings suggest that young subjects with relatively long-lasting T1DM have a generalized preclinical involvement of large artery structure and function, as well as a blunted endothelium regenerating capacity. Hyperglycemia and suboptimal chronic glycemic control seem to deteriorate the functional arterial characteristics, such as large arteries stiffness, wave reflection and peripheral endothelium-dependent vasodilation, whereas an impaired endothelium regenerating capacity and adiponectin levels seem to influence arterial structure.

Growth outcome during GnRH agonist treatments for slowly progressive central precocious puberty.

BACKGROUND: Gonadotropin-releasing hormone agonists (GnRHa) represent the gold-standard treatment for central precocious puberty (CPP). In CPP children, GnRHa treatment slows bone age progression and preserves adult height (Ht) by suppressing sexual steroid secretion. In some patients, however, GnRHa induce an inappropriate growth deceleration impairing Ht outcome. Furthermore, slowly progressive CPP (spCPP) forms were reported which do not need GnRHa treatment. METHODS: We evaluated the growth outcome of 26 spCPP girls treated with triptorelin (TR) and 21 with leuprorelin acetate (LA) for 36.5 +/- 0.7 months. RESULTS: GnRHa treatment induced a progressive growth deceleration in both spCPP groups. No difference in bone maturation was detected (p > 0.05; TR vs. LA group), however compared to LA, TR treatment resulted in significantly higher Ht after 24 months (p < 0.05; LA vs. TR group). Although target height (TH) standard deviation score (SDS) and predicted adult height (PAH)-SDS at diagnosis were similar in both spCPP groups (p > 0.05; LA vs. TR group), final height (FH-SDS) was lower in LA-treated subjects (p < 0.05; LA vs. TR group). In both spCPP groups, FH-SDS was significantly lower than TH-SDS (p < 0.001) but not lower than PAH-SDS at diagnosis (p > 0.05). Ht-SDS correlated with 17beta-estradiol (E(2)) blood levels in both spCPP groups (p < 0.0001) throughout GnRHa treatment, and E(2) values were higher in the TR- than in the LA-treated patients during the 12 months after GnRHa administration (p < 0.05; LA vs. TR group). GnRHa-induced E(2) secretion and Ht-SDS at GnRHa withdrawal correlated positively with FH (p < 0.01 and p < 0.001, respectively). CONCLUSIONS: The effectiveness of GnRHa treatment in improving FH in spCPP girls was doubtful.

Sex steroidal targets & genetic susceptibility to idiopathic cryptorchidism.

UNLABELLED: Cryptorchidism, the most common congenital abnormality in newborn boys, is a major risk factor for male infertility and testicular malignancy in adulthood. This disorder appears as an isolated form or as part of impaired male sex development or a congenital malformation syndrome. Based mainly on the laboratory studies of the rodent models, sex steroidal signaling pathways have been shown to be involved in testicular descent; however, data on the human genetic susceptibility are less compelling. Mutations in the human genes encoding androgen receptor (AR), estrogen receptor alpha (ERalpha) and beta (ERbeta), and steroidogenic factor-1 (SF-1) have occasionally been identified but do not seem to be a frequent cause of this genital malformation. On the other hand, common polymorphisms in these genes have recently been investigated as possible contributing risk factors for idiopathic isolated (nonsyndromic) cryptorchidism, alone or by influencing susceptibility to other causal factors such as environmental endocrine disruptors. ABBREVIATIONS: Androgen Receptor (AR); DNA-Binding Domain (DBD) ;Environmental Estrogen Disruptors (EEDs); Estrogen Receptor Alpha (ERalpha); Estrogen Receptor Beta (ERbeta); Ligand-Binding Domain (LBD); Linkage Disequilibrium (LD); Odds Ratio (OR); Restriction Fragment Length Polymorphism (RFLP); Single Nucleotide Polymorphism (SNP); Steroidogenic Factor-1 (SF-1); Transactivation Domain (TAD); Testicular Dysgenesis Syndrome (TDS); Wild Type (WT).

Rickets in the Middle East: role of environment and genetic predisposition.

CONTEXT: The Middle East has a high incidence of rickets, and it is also common in Europe-dwelling children of Middle Eastern origin. OBJECTIVE: The objective of the study was to explore the mechanisms leading to rickets in children of the Middle East. DESIGN AND SETTING: We conducted a prospective study in 98 rachitic and 50 controls (aged 6 months to 4 yr) from university and community outpatient hospitals in Egypt and Turkey. MAIN OUTCOME MEASURES: We collected epidemiological, maternal, nutritional, radiographic, and biochemical parameters; markers of bone turnover; and vitamin D receptor (VDR) gene polymorphisms. RESULTS: Epidemiological factors had a key role in pursuit of rickets; Egyptian and Turkish patients had lower (P < 0.01) dietary calcium intake than controls and the recommended dietary intakes, and serum 25-hydroxyvitamin D levels were reduced in patients, the difference with controls being significant (P < 0.001) only in Turkey, although rickets was more severe in Egypt as determined by the x-ray score (P < 0.05). In Turkey, the F VDR allele frequency was significantly (P < 0.05) increased in patients. The BB VDR genotype was associated with lower serum 25-hydroxyvitamin D levels in both patients and controls and with severity of rickets. CONCLUSIONS: In Turkey most patients had vitamin D deficiency, whereas in Egypt they had mostly calcium insufficiency combined with vitamin D deficiency. In this environ, VDR genotypes may predispose to rickets by increased frequency of the F allele. The unique environs and genetic predisposition have to be accounted for in the design of preventive measures, rather than using European or American recommended dietary intake for calcium and vitamin D.

High growth rate of girls with precocious puberty exposed to estrogenic mycotoxins.

OBJECTIVE: To test the hypothesis that human puberty timing can be advanced by environmental estrogen exposure. STUDY DESIGN: We analyzed serum mycoestrogen contamination via high-performance liquid chromatography (HPLC) in 32 girls affected by central precocious puberty (CPP) and in 31 healthy female control subjects. All 32 patients received triptorelin (TR) for more than 12 months after diagnosis. RESULTS: Increased serum levels of zearalenone (ZEA; 933.7 +/- 200.3 pg/mL; 95% CI, 723.5-1143.9) and of its congener alpha-zearalenol (106.5 +/- 1.9 pg/mL; 95% CI, 104.5-108.5) contaminated 6 girls with CPP, who were from a bounded Tuscany area. At diagnosis, ZEA levels correlated with patient height (r = 0.906, P < .05) and weight (r = 0.887, P < .05), but not with bone age. In patients who were mycotoxin-positive, height (F = 4.192; P < .01), weight (F = 3.915; P < .01), and height velocity (F = 2.777, P < .05) were higher than patients who were mycotoxin-negative during 12-months TR treatment. Height correlated with weight both in patients who were mycotoxin-positive (r = 0.986, P < .001) and in patients who were mycotoxin-negative (r = 0.994, P < .001). Body mass index, bone age, and gonadal secretion was not different in patient groups before and during TR treatment (P > .05). CONCLUSIONS: Mycoestrogenic zearalenone is suspected to be a triggering factor for CPP development in girls. Because of its chemical resemblance to some anabolic agents used in animal breeding, ZEA may also represent a growth promoter in exposed patients.

No evidence of chromosome damage in children and adolescents with differentiated thyroid carcinoma after receiving 131I radiometabolic therapy, as evaluated by micronucleus assay and microarray analysis.

PURPOSE: As (131)I therapy, used to achieve ablation of thyroid gland remnant, can cause chromosome damage in cultured peripheral lymphocytes especially, we investigated whether administration of radioiodine may induce early genome damage in peripheral T lymphocytes of adolescents with differentiated thyroid carcinoma (DTC). METHODS: We studied 11 patients, aged 14.8 +/- 3.1 years, who assumed (131)I (range: 1.11-4.44 GBq) to ablate thyroid remnant. A blood sample for micronucleus assay and for evaluating expression of some genes involved in the DNA repair or the apoptosis pathways was obtained from each patient 1 h before (T(0)) and 24 (T(1)) and 48 h (T(2)) post-radioiodine administration. RESULTS: Compared to T(0), we did not find any difference in the number of micronucleated cells at both T(1) and T(2) in any subject. Nine out of 11 patients had altered expression levels in a majority of the DNA repair and apoptosis genes at T(1), which decreased at T(2). CONCLUSIONS: We demonstrated for the first time that peripheral cells of DTC children and adolescents who received (131)I at a mean dosage of 3.50 +/- 0.37 GBq did not show chromosome damage within 48 h from the end of radiometabolic therapy. This may be due to a prompt activation of the cell machinery that maintains the integrity of the genome to prevent harmful double-strand breaks from progressing to chromosome mutations, either by repairing the lesions or by eliminating the most seriously damaged cells via apoptosis.

Vitamin D in pediatric age: consensus of the Italian Pediatric Society and the Italian Society of Preventive and Social Pediatrics, jointly with the Italian Federation of Pediatricians.

Vitamin D plays a pivotal role in the regulation of calcium-phosphorus metabolism, particularly during pediatric age when nutritional rickets and impaired bone mass acquisition may occur.Besides its historical skeletal functions, in the last years it has been demonstrated that vitamin D directly or indirectly regulates up to 1250 genes, playing so-called extraskeletal actions. Indeed, recent data suggest a possible role of vitamin D in the pathogenesis of several pathological conditions, including infectious, allergic and autoimmune diseases. Thus, vitamin D deficiency may affect not only musculoskeletal health but also a potentially wide range of acute and chronic conditions. At present, the prevalence of vitamin D deficiency is high in Italian children and adolescents, and national recommendations on vitamin D supplementation during pediatric age are lacking. An expert panel of the Italian Society of Preventive and Social Pediatrics reviewed available literature focusing on randomized controlled trials of vitamin D supplementation to provide a practical approach to vitamin D supplementation for infants, children and adolescents.

Diagnosis, treatment and prevention of pediatric obesity: consensus position statement of the Italian Society for Pediatric Endocrinology and Diabetology and the Italian Society of Pediatrics.

The Italian Consensus Position Statement on Diagnosis, Treatment and Prevention of Obesity in Children and Adolescents integrates and updates the previous guidelines to deliver an evidence based approach to the disease. The following areas were reviewed: (1) obesity definition and causes of secondary obesity; (2) physical and psychosocial comorbidities; (3) treatment and care settings; (4) prevention.The main novelties deriving from the Italian experience lie in the definition, screening of the cardiometabolic and hepatic risk factors and the endorsement of a staged approach to treatment. The evidence based efficacy of behavioral intervention versus pharmacological or surgical treatments is reported. Lastly, the prevention by promoting healthful diet, physical activity, sleep pattern, and environment is strongly recommended since the intrauterine phase.

A Case of 22q11 Deletion Syndrome (22q11DS) with a Panayiotopoulos Epileptic Pattern: Are Additional Copy-Number Variations a Possible Second Hit in Modulating the 22q11DS Phenotype?

"22q11 deletion syndrome" (22q11DS) is a rare genetic syndrome, in which most patients share the same deletion, but their clinical features may vary a great deal. The genetic mechanisms underlying the variable expressivity and reduced penetrance of 22q11DS still have to be fully elucidated. Epilepsy has been reported in about 15.2% of the patients; however, few studies have focused on this topic, and in most cases, a detailed epileptic profile is missing. Since only a minority of patients experience epileptic seizures, 22q11deletion can be considered a predisposing factor, which is not sufficient "per se" to cause epilepsy; to date, no candidate gene for epilepsy has been identified in the deleted region. We report on a 6-year-old girl with 22q11DS presenting a form of epilepsy that can be classified as "Panayiotopoulos syndrome." Array CGH revealed an additional microduplication of 172 kb in 2q37, harboring three genes. One of these, DGKD (diacylglycerol kinase delta), is interrupted by the distal breakpoint of the duplication. DGKD encodes a cytoplasmic enzyme that phosphorylates diacylglycerol to produce phosphatidic acid. This is an important second messenger in a pathway of lipid signaling that has been implicated in epilepsy and other neurological diseases. Disruption of DGKD by a t(X;2) has been previously reported in a patient with epilepsy. The 2q37 microduplication was inherited from her mother, who never experienced epileptic seizures, thus this imbalance is not "per se" sufficient to cause epilepsy. It can be hypothesized that the epileptic phenotype is provoked by the simultaneous presence of 22q11.2 deletion and 2q37 duplication. It has been shown that rare additional copy-number variations (CNVs) outside the 22q11.2 region may modulate the risk of congenital heart defects. It is possible that also for the epileptic phenotype, the additional CNVs may represent an important modifying factor underlying the variable expressivity and incomplete penetrance in the 22q11DS.

Cross-sectional reference data for phalangeal quantitative ultrasound from early childhood to young-adulthood according to gender, age, skeletal growth, and pubertal development.

Bone mineral status by phalangeal quantitative ultrasound (QUS, DBM Sonic, IGEA, Carpi, Modena, Italy) was examined in 3044 (1513 males and 1531 females) healthy subjects, aged 2-21 years. The aim of the study was to provide a reference database for phalangeal QUS parameters, amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT), both expressed as centiles and Z score, according to gender, age, height, weight, body mass index (BMI), and pubertal stage to be used for estimating bone mineral status in patients with disorders of growth or of bone and mineral metabolism. In both sexes, AD-SoS and BTT increased significantly (P<0.0001) according to all the anthropometric variables. Females showed higher values than males in the age groups 9-14 for AD-SoS (P<0.04-P<0.0001) and in the age groups 11-13 for BTT (P<0.02). Males had higher BTT values than females in the age groups 6-8 and 15-21 (P<0.04-P<0.0001). AD-SoS was higher (P<0.02-P<0.0001) in females than in males at pubertal stages 2, 3, and 4, but it was higher (P=0.001) in males compared with females at pubertal stage 5. BTT was higher in males than females at pubertal stages 1 (P<0.0001), 2 (P<0.01), and 5 (P<0.0001). In both sexes, AD-SoS and BTT were significantly correlated between them (r=0.92, P<0.0001) and with all the anthropometric variables (r=0.53-r=0.85, P<0.0001). Age, weight, BMI, and pubertal stage were independent predictors of AD-SoS in males; age and pubertal stage were independent predictors of AD-SoS in females. In both sexes, height and pubertal stage, and also age only in females, were independent predictors of BTT. In conclusion, our data show that gender, age, height, and timing of sexual maturation are main determinants of bone structure and geometry, and that both these two processes may be captured by phalangeal QUS. It may be a useful tool to assess bone mineral status from early childhood to young-adulthood with a very small confounding effect related to bone sizes and without exposing the subjects to a source of radiation.