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A 3-month-old, full term female infant, adequate for gestational age, and exclusively breastfed, was admitted with a 10 day history of generalised scaling erythematous dermatitis, affecting the face (perinasal, nasolabial folds and periauricular), acral and intertriginous areas, with irritability and failure to thrive. Her mother had been treated with isoniazid since the third trimester because of family contact with tuberculosis. Based on a diagnosis of suspected impetiginised eczema, the infant was treated with flucloxacillin and prednisolone, and maternal isoniazid was suspended, with no improvement. Investigations found low serum zinc levels in the infant (33 μg/dL; normal range (NR) >60 μg/dL), normal plasma zinc levels in the mother (111.3 μg/dL; NR 68–120 μg/dL) and lower than the normal range of zinc levels in breast milk (270μg/L; NR 1000–2500 μg/L), suggesting acrodermatitis caused by zinc deficiency. Oral zinc supplementation (3 mg/kg/day) was started with a marked improvement in skin lesions, as well as good weight gain. At the age of 6 months, after food diversification, supplementation was suspended, without any recurrence of symptoms.

Transitions between epithelial and mesenchymal cellular states (EMT/MET) contribute to cancer progression. We hypothesize that EMT followed by MET promotes cell population heterogeneity favouring tumour growth. We developed an EMT model by on/off exposure of epithelial EpH4 cells (E-cells) to TGFβ1 that mimics phenotypic EMT (M-cells) and MET. We aimed at understanding whether phenotypic MET is accompanied by molecular and functional reversion back to epithelia, by using RNA sequencing, Immunofluorescence (IF), proliferation, wound healing, focus formation and mamosphere formation assays, as well as cell-xenografts in nude mice. Phenotypic reverted-epithelial cells (RE-cells), obtained after MET induction, presented pure epithelial morphology and proliferation rate resembling E-cells. However, RE transcriptomic profile and IF staining of epithelial and mesenchymal markers revealed a unique and heterogeneous mixture of cell-subpopulations, with high self-renewal ability fed by oxidative phosporylation. RE-cells heterogeneity is stably maintained for long periods after TGFβ1 removal, both in vitro and in large derived tumours in nude mice. Overall, we show that phenotypic reverted-epithelial cells (RE-cells) do not return to the molecular and functional epithelial state, present mesenchymal features related with aggressiveness and cellular heterogeneity that favour tumour growth in vivo. This work strengthens epithelial cells reprogramming and cellular heterogeneity fostered by inflammatory cues as a tumour-growth promoting factor in vivo.

Henoch–Schönlein purpura (HSP) is characterized by nonthrombocytopenic palpable purpura, arthritis or arthral­gia, and gastrointestinal and/or renal involvement. Gastrointestinal symptoms are reported in 50%-75% and they are related to a previous group A streptococcal infection in 40%. A healthy 5-year-old girl presented with a three-week history of a recurrent purpuric rash on the lower limbs, ar­thralgia and angioedema, without renal involvement. During the third relapse, she had severe, diffuse and persistent abdominal pain and bloody stools. An abdominal ultrasound revealed transmural edema of the last ileal segment, compatible with ileitis. She received prednisolone for five days, with full clinical recovery. Antistreptolysin O titer was elevated. The remaining laboratory tests were normal (antinuclear, anti-neutrophil and anti-Saccharomyces cerevisiae antibodies; rheumatoid factor; stool cultures, parasitological examination and viral antigen tests). One month later, an abdominal ultrasound revealed no abnormalities. Terminal ileitis is a very rare complication of HSP in children but has a good prognosis.

Funding Acknowledgements Type of funding sources: Other. Main funding source(s): MG and CS were supported by a PhD FCT grant (SFRH/BD/128893/2017) and by an individual grant from CAPES [BEX 0554/14-6], respectively. This work was financially supported by the project POCI-01-0145-FEDER-030011, funded by FEDER, through COMPETE2020-POCI, and by national funds, through FCT/MCTES (PTDC/MEC-CAR/30011/2017). iBiMED is a research unit supported by the Portuguese Foundation for Science and Technology (REF: UID/BIM/04501/2020) and FEDER/Compete2020 funds). Introduction Amyloid-like protein aggregates play a decisive role in the pathology of heart failure. Alterations in protein homeostasis, in particular, the clearance of toxic amyloid-like aggregates are emerging therapeutic targets in cardiovascular medicine. The clinical benefits of cardiac rehabilitation and exercise training are widely accepted in heart failure; however, little is known about the potential benefit of exercise training in amyloid-like protein aggregates. Purpose To assess the effects of a moderate-intensity exercise training program on amyloid-like protein aggregates levels among patients with heart failure with reduced ejection fraction. Methods Eighteen subjects participated in the study; eight patients (age: 66.6 ± 5.9 years; FEVE: 38.4 ± 8.9%) with heart failure with reduced ejection fraction participated in a 3-month exercise training program (2 x 60 min sessions per week of moderate-intensity aerobic and resistance exercise). Ten healthy subjects (age: 68. 4 ± 3.1 years) were recruited to an age-matched reference group. Amyloid-like protein aggregates were assessed before and after 3 months of exercise training. Clinical data, medication, anthropometrics, and cardiorespiratory fitness were also assessed. Thioflavin T (ThT) dye fluorescence was used to quantify the plasma levels of amyloid-like aggregates and the Fourier transform infrared spectroscopy (FTIR) was applied to evaluate the conformation of cross-β-sheet structures characteristic of amyloid protein aggregates. Results Exercise program improved cardiorespiratory fitness by 14.0 ± 17.1% (17.4 ± 3.2 to 19.7 ± 2.9 ml/kg/min) and reduced NT-proBNP levels by 16.5% (34.2) (median concentration of 632 pg/mL (720.8) to 517.5 pg/mL (707.0)) in the heart failure patients. A slight decrease of amyloid-like aggregates levels was observed in post-exercise training samples (a reduction of 3.1%); interestingly, after the exercise training program, the heart failure patients showed levels of amyloid-like aggregates similar to the reference group (1132.0 ± 114.2 vs. 1094.8 ± 132.9 a.u.). Additionally, the PLS-R multivariate analysis of the amide I region of the FTIR spectra revealed enrichment of antiparallel β-sheets (1693 cm-1) assigned to amyloid-like oligomers in the samples of heart failure patients before, but not after, the exercise program. Of note, oligomeric species, as intermediates of amyloid assembly, can contribute to the increase of amyloid burden, but also, some have been reported to be highly reactive and toxic to cells, being key elements of amyloid pathogenesis. Conclusions Our preliminary results indicate that 3 months of exercise training may have significant effects on amyloid-like oligomers, and start hindering the formation of the larger ThT-positive aggregates among patients with heart failure. Abstract Figure.

Introduction With the widespread introduction of conjugate meningococcal and pneumococcal vaccines, the prevalence and etiology of invasive bacterial infections have changed. We aimed to review all cases of bacteremia in a level II pediatric department over a ten-year period in the post-pneumococcal conjugate vaccine era. Methods We reviewed all positive blood cultures (BC) obtained in our department between 2007 and 2016. Results were classified as contaminants, potential pathogens or confirmed pathogens, based on species, number of positive BC in the episode and the patients’ medical history. Demographic and clinical data were collected for patients with identified pathogens. Results A total of 638 positive BC were identified (6.6% of total BC); 120 (1.2%) were considered to represent true bacteremia. The most frequently identified microorganism was Streptococcus pneumoniae (29.2%), with a decrease in the number of cases between 2008 and 2015. Staphylococcus aureus was the second most common organism (19.2%) being 21.7% of these methicillin-resistant. Escherichia coli was the most common isolate in children aged less than three months. Conclusion We found a rate of true bacteremia in children similar to recent studies. Although Streptococcus pneumoniae remains the most common microorganism, its prevalence may be declining. Monitoring microbiological data in children has implications in practice, particularly in local antibiotic prescription.

Background Pre-infarct angina (PIA) has been shown to reduce reperfusion injury and infarct size in patients with ST-elevation myocardial infarction (STEMI) and currently represents the most efficient form of myocardial conditioning yet discovered. The role of diabetes on ischemic preconditioning remains controversial – while some pre-clinical studies suggest that diabetes blunts ischemic conditioning, clinical studies are lacking. Methods We retrospectively evaluated consecutive patients with STEMI admitted in our hospital from January 2008 to August 2018 who underwent primary angioplasty (PCI). PIA was defined as chest, arm or jaw pain during the preceding 48h before STEMI diagnosis. Peak creatine kinase and peak Troponin T levels were used as a surrogate of infarct size. Ischemic time (IT) was defined as the time between the onset of symptoms to the restoration of flow after either guidewire passage, thrombus aspiration or first balloon inflation. Results Of the 1143 included patients, 74% (n=845) were male and mean age was 62.6±13.1 years. A quarter of STEMI-patients had diabetes (25%, n=285). Almost a third of the patients (32%, n=359) had a history of angina in the preceding 48h before STEMI (PIA). The proportion of PIA was similar between diabetic and non-diabetic patients. In patients with diabetes, PIA was associated with lower creatine kinase (CK) (1144 [500–2212] vs 1715 [908–3309] U/L, p=0.0029) and Troponin T (TnT 3.30 [1.90–6.58] vs 4.88 [2.50–9.58] ng/mL, p=0.0022) despite similar IT as compared to those without PIA (328 [200–554] vs. 258 [180–530] minutes, p=0.1365). In non-diabetic patients, PIA was not significantly associated with infarct size (TnT 3.74 [2.23–7.11] vs 4.56 [2.44–7.77] ng/mL, p=0.1945; CK 1549 [910 - 2909] vs 1793 [996 - 3078] U/L, p=0.0653) even after adjustment for the increased ischemic time (240 [150–550] vs. 210 [140–405] minutes, p=0.0128) (β=−0.12, p=0.085 for CK and β=−0.11, p=0.183 for TnT). A significant interaction was observed between the existence of PIA and diabetes on peak TnT (p=0.026 for interaction) and CK (p=0.047 for interaction), which was independent of the culprit vessel and IT. During a median follow-up period of 18.0 [12.1–25.5] months, 268 (24.0%) MACE events have occurred (165 deaths, 27 strokes, 46 myocardial infarctions and 26 target vessel revascularization). PIA was associated with a significant reduction in the incidence of MACE (HR 0.66 (95% CI: 0.48–0.89)) driven by a reduction on mortality (HR 0.44 (95% CI: 0.28–0.70)). Diabetes was associated with an increased incidence of MACE (HR 1.42 (95% CI: 1.07–1.89)). No interaction was found between diabetes and PIA on their effect on MACCE events. Conclusion PIA is a strong predictor of favourable outcomes in the setting of STEMI. The effect of PIA on myocardial protection in patients with STEMI undergoing primary PCI seems to be modulated by the presence of diabetes. Distribution of Peak CK and Peak TnT Funding Acknowledgement Type of funding source: None

Background The supracondylar fracture of the humerus is one of the most common fractures in pediatric age. Many classifications were proposed, with Gartland being the most widely used one and Lagrange and Rigault (L&R) the most used in French-speaking countries. Objectives The goal of this study was to compare the Wilkins-modified Gartland classification with the L&R classification in terms of reproducibility. Methods Three observers with similar training levels classified 35 fractures according to both classifications twice to evaluate both intra and interobserver variation. Results The mean intraobserver variation was 0.78 and 0.77 for Gartland and L&R classifications, respectively, and the mean interobserver variation was 0.55 and 0.62 for Gartland and L&R classifications, respectively. Conclusions Both classifications reveal adequate to usage in clinical and investigational practices, which is consistent with the literature.

Rhinovirus is a common picornavirus with over 150 serotypes and three species, which is responsible for half of the human common cold cases. In people with chronic respiratory conditions and elders, it may also cause life-threatening diseases. Transmission routes are not definitively established but may involve direct human-to-human and indirect transmission (surfaces and aerosols based). In the present study, year-long presence of virus was tested by qPCR in the nostrils of young healthy volunteers and indoor and outdoor air samples. Results were correlated to atmospheric conditions (meteorological and air quality parameters) and voluntaries immune system-related genetic polymorphisms (TOLLIP rs5743899, IL6 rs1800795, IL1B rs16944, TNFA rs1800629) typed by PCR-RFLP. Nasal samples showed increased frequency and viral titers of Rhinovirus in spring and autumn. No indoor air samples tested positive for Rhinovirus, whereas outdoor air samples tested positive in late autumn. Sun radiation, atmospheric SO2, and benzene levels correlated with nostrils Rhinovirus detection. Both IL6 and TOLLIP polymorphisms but not TNFA or IL1B influenced Rhinovirus detection in the nostrils of voluntaries. Taken together, the results indicate that Rhinovirus circulation is determined by environmental conditions (weather, air-borne virus, and air pollution) and genetically encoded individual variation in immunity.

Vaginal bleeding can occur shortly after delivery in 3%–5% of newborns as a consequence of placental hormone withdrawal . Although usually benign, its differential diagnosis includes central precocious puberty, tumours and other pathological conditions. A girl born at 26 weeks of gestation presented with five episodes of vaginal bleeding, each lasting less than a week, initiated at 4 months of age. Luteinising hormone and oestradiol levels were in the pubertal range. Later, she exhibited breast development, with no other pubertal signs. An ultrasonography test revealed an impregnated endometrium and a right ovarian cyst with 43 mm of diameter. A cranioencephalic MRI was unremarkable. Clinicians adopted expectant management and there was clinical, hormonal and radiological resolution in 3 months. The spontaneous resolution suggested mini-puberty of infancy. This is usually an asymptomatic condition, but to date, four cases of an exacerbated form in extremepremature infants have been reported. Long-term follow-up data are missing.A girl born at 26 weeks of gestation presented with five episodes of vaginal bleeding, each lasting less than a week, initiated at 4 months of age. Luteinising hormone and oestradiol levels were in the pubertal range. Later, she exhibited breast development, with no other pubertal signs. An ultrasonography test revealed an impregnated endometrium and a right ovarian cyst with 43 mm of diameter. A cranioencephalic MRI was unremarkable. Clinicians adopted expectant management and there was clinical, hormonal and radiological resolution in 3 months. The spontaneous resolution suggested mini-puberty of infancy. This is usually an asymptomatic condition, but to date, four cases of an exacerbated form in extremepremature infants have been reported. Long-term follow-up data are missing.

Deregulation of tRNAs, aminoacyl-tRNA synthetases and tRNA modifying enzymes are common in cancer, raising the hypothesis that protein synthesis efficiency and accuracy (mistranslation) are compromised in tumors. We show here that human colon tumors and xenograft tumors produced in mice by two epithelial cancer cell lines mistranslate 2- to 4-fold more frequently than normal tissue. To clarify if protein mistranslation plays a role in tumor biology, we expressed mutant Ser-tRNAs that misincorporate Ser-at-Ala (frequent error) and Ser-at-Leu (infrequent error) in NIH3T3 cells and investigated how they responded to the proteome instability generated by the amino acid misincorporations. There was high tolerance to both misreading tRNAs, but the Ser-to-Ala misreading tRNA was a more potent inducer of cell transformation, stimulated angiogenesis and produced faster growing tumors in mice than the Ser-to-Leu misincorporating tRNA. Upregulation of the Akt pathway and the UPR were also observed. Most surprisingly, the relative expression of both misreading tRNAs increased during tumor growth, suggesting that protein mistranslation is advantageous in cancer contexts. These data highlight new features of protein synthesis deregulation in tumor biology. published

Congenital aniridia is a rare genetic disorder characterized by varying degrees of iris hypoplasia that are associated with additional ocular abnormalities. More than 90% of the causal mutations identified are found in the PAX6 gene, a transcription factor of critical importance in the process of neurogenesis and ocular development. Here, we investigate clinical, molecular, and craniofacial features of a large Brazilian family with congenital aniridia. Among the 56 eyes evaluated, phenotype variation encompassed bilateral total aniridia to mild iris defects with extensive variation between eyes of the same individual. PAX6 molecular screening indicated a heterozygous splice mutation (c.141 + 1G>A). Thus, we hypothesize that this splicing event may cause variation in the expression of the wild-type transcript, which may lead to the observed variation in phenotype. Affected individuals were more brachycephalic, even though their face height and cephalic circumference were not significantly different when compared to those of non-affected relatives. From this, we infer that the head shape of affected subjects may also be a result of the PAX6 splice-site mutation. Our data summarize the clinical variability associated with the ocular phenotype in a large family with aniridia, and help shed light on the role of PAX6 in neurocranial development. Fil: Fernandes Lima, Z.S.. Universidade Federal do Rio Grande do Sul; Brasil Fil: Paixão-Côrtes, V.R.. Universidade Federal do Rio Grande do Sul; Brasil Fil: de Andrade, A.K.M.. Faculdade de Medicina; Brasil Fil: Fernandes, A.S.. Universidade Federal de Alagoas; Brasil Fil: Coronado, B.N.L.. Universidade Federal de Alagoas; Brasil Fil: Monte Filho, H.P.. Universidade Federal de Alagoas; Brasil Fil: Santos, M.J.. Universidade Federal de Alagoas; Brasil Fil: Omena Filho, R.L.. Universidade Federal de Alagoas; Brasil Fil: Biondi, Facundo Carmelo. Universidade Federal do Rio Grande do Sul; Brasil Fil: Ruiz Linares, A.. University College London; Estados Unidos Fil: Ramallo, Virginia. Universidade Federal do Rio Grande do Sul; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Hunemeier, T.. Universidade Federal do Rio Grande do Sul; Brasil Fil: Schuler Faccini, L.. Universidade Federal do Rio Grande do Sul; Brasil Fil: Monlleo, I.L.. Universidade Federal de Alagoas; Brasil

The urinary tract infections associated with catheterization are very common in hospital and home care contexts. Currently there are several recommendations for its prevention, however, when approaching the kind of solute used in the urinary meatus prior to catheterization doubts continue to persist. Thus this study aimed at determining the effectiveness of cleaning the urinary meatus with water or saline comparing to its sterilization through a systematic review and meta-analysis. In order to do so, the principles proposed by the Cochrane Handbook were followed, a critical analysis was conducted by two researchers and the statistical analysis was performed with the use of STATA 11.1. We concluded that the cleaning or disinfection of the urinary canal prior to bladder catheterization is not statistically significant (OR=1.07, CI 95%=0.68-1.68, p=0.779) and that there is some evidence that the use of water/saline reduces rates of UTI (urinary tract infection).

Invasive pneumococcal disease predominantly affects younger children, elderly, and immunocompromised patients. Pneumococcal meningitis is a particularly important form of presentation, considering its high rate of morbimortality. We present the case of a previously healthy 12-year-old adolescent male who was hospitalized due to suspicion of osteoarticular infection in his left foot. A few hours later, he developed meningeal signs, exhibiting slight pleocytosis andStreptococcus pneumoniaeisolates in both cerebrospinal fluid and blood. Imaging studies were inconclusive regarding the nature of the foot disorder. We considered the hypothesis of osteomyelitis of the navicular bone as the most likely, for which he completed six weeks of antibiotic therapy. There was a favorable clinical evolution, along with complete absence of osteoarticular or neurological sequelae. The relevance of this clinical case resides in the unusual presentation of invasive pneumococcal disease in this age group, as well as in the rare form of orthopedic involvement.

// Ilaria Guerriero 1 , Daniela D’Angelo 2 , Pierlorenzo Pallante 2 , Mafalda Santos 1 , Marianna Scrima 1 , Donatella Malanga 3 , Carmela De Marco 3 ,Maria Ravo 4 , Alessandro Weisz 4 , Carmelo Laudanna 3 , Michele Ceccarelli 1, 5 , Geppino Falco 1, 6 , Antonia Rizzuto 7 , Giuseppe Viglietto 1, 3 1 Biogems.c.ar.l., Istituto di Ricerche Genetiche “Gaetano Salvatore”, Ariano Irpino, Avellino, Italy 2 Istituto per l’Endocrinologia e l’Oncologia Sperimentale, IEOS-CNR, c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universita “Federico II” of Napoli, Napoli, Italy 3 Dipartimento di Medicina Sperimentale e Clinica, Universita Magna Graecia of Catanzaro, Italy 4 Laboratorio di Medicina Molecolare e Genomica, Dipartimentodi Medicina e Chirurgia, Universita di Salerno, Baronissi, Italy 5 Department of Biological and Environmental Studies, Universita del Sannio, Benevento, Italy 6 Dipartimento di Biologia, Universita degli Studi di Napoli Federico II, Complesso Universitario Monte S.Angelo, Napoli, Italy 7 Dipartimento di Scienze Mediche e Chirurgiche, Universita Magna Graecia of Catanzaro, Italy Correspondence to: Giuseppe Viglietto, email: viglietto@unicz.it Keywords: NSCLC, PI3K/AKT, microRNA, miR-196a Received: January 11, 2016 Accepted: November 02, 2016 Published: November 17, 2016 ABSTRACT Hyperactivation of the PI3K/AKT pathway is observed in most human cancer including lung carcinomas. Here we have investigated the role of miRNAs as downstream targets of activated PI3K/AKT signaling in Non Small Cell Lung Cancer (NSCLC). To this aim, miRNA profiling was performed in human lung epithelial cells (BEAS-2B) expressing active AKT1 (BEAS-AKT1-E17K), active PI3KCA (BEAS-PIK3CA-E545K) or with silenced PTEN (BEAS-shPTEN). Twenty-four differentially expressed miRNAs common to BEAS-AKT1-E17K, BEAS-PIK3CA-E545K and BEAS-shPTEN cells were identified through this analysis, with miR-196a being the most consistently up-regulated miRNA. Interestingly, miR-196a was significantly overexpressed also in human NSCLC-derived cell lines (n=11) and primary lung cancer samples (n=28). By manipulating the expression of miR-196a in BEAS-2B and NCI-H460 cells, we obtained compelling evidence that this miRNA acts downstream the PI3K/AKT pathway, mediating some of the proliferative, pro-migratory and tumorigenic activity that this pathway exerts in lung epithelial cells, possibly through the regulation of FoxO1, CDKN1B (hereafter p27) and HOXA9.

We report the case of a 50-year-old woman with systemic lupus erythematosus who had previously undergone pacemaker implantation. She developed recurrent pulmonary thromboembolism and was diagnosed with antiphospholipid syndrome. During investigation, pacemaker endocarditis was discovered, and the system was surgically explanted. Surprisingly, all microbiological studies, including culture of the extracted material and extensive serological analysis, were negative and she remained well with anticoagulation plus her usual immunosuppressant regimen.The data indicate that her pacemaker endocarditis could be an equivalent of the nonbacterial thrombotic endocarditis often described in native valves. Resumo: Descreve-se o caso de uma doente de 50 anos com lúpus eritematoso sistémico e história prévia de implantação de pacemaker. Esta desenvolveu tromboembolismo pulmonar recorrente, tendo-lhe sido diagnosticada síndrome antifosfolipídica. Durante a investigação foi descoberta uma endocardite de pacemaker, tendo sido sujeita a extracção cirúrgica do sistema. Inesperadamente, todos os exames microbiológicos, incluindo culturas do material removido, e extensa análise serológica, foram negativos, tendo a doente se mantido clinicamente estável com anticoagulação oral e o habitual regime imunossupressor.Os dados indicam que a esta endocardite de pacemaker poderá ser um equivalente da endocardite trombótica não bacteriana, habitualmente descrita em válvulas nativas. Keywords: Pacemaker, Endocarditis, Antiphospholipid syndrome, Palavras-chave: Pacemaker, Endocardite, Síndrome antifosfolipídica

Sternoclavicular arthritis is an unusual osteoarticular infection and can be associated with severe complications. Cases in a paediatric population are infrequently reported, making this approach challenging. Kingella kingae is an agent of increasing recognition in paediatric invasive infections, principally below 2 years of age. A case of K. kingae osteoarthritis in a 17-month-old child is described with a review of the literature.

Background. Trichorhinophalangeal syndrome (TRPS) is an autosomal dominant skeletal dysplasia caused by defects involving the TRPS1 gene. Three types (TRPSs I, II, and III) have been described, exhibiting the common triad of hair, craniofacial, and skeletal abnormalities. TRPS II includes the additional characteristics of mental retardation and multiple exostoses.Case Report. We describe a sporadic case of TRPS type I in a child with two novel nonsense pathogenic mutations in the TRPS1 gene, both in heterozygosity—c.1198C>T (p. Gln400X) and c.2086C>T (p.Arg696X). None of these mutations were found in her parents. Clinical presentation included typical hair and facial features, as well as slight skeletal abnormalities.Discussion. There is a wide variability in clinical expression of TRPS I. Manifestations of the disease can be subtle, yet skeletal anomalies imply that TRPS I is more than an esthetic problem. Clinical and genetic diagnosis allows adequate followup and timely therapeutic procedures. When a single mutation was sufficient for the onset of the disease, our patient presented two different ones.

Epidermal Nevus Syndrome (ENS) is characterized by epidermal nevi associated with abnormalities involving the nervous, skeletal, and other systems. Rarely, hypophosphatemic rickets has been observed in association with epidermal nevi. A patient with ENS with right-sided serpiginous skin lesions, generalized weakness, and diffuse osteopenia associated with hypophosphatemic rickets is described. Medical management was enough to correct the clinical picture. The pathogenic mechanism involved in the onset of hypophosphatemic rickets in ENS is not fully clarified. Different studies suggest that phosphaturia, caused by circulating factor(s), called "phosphatonin(s)," may be secreted by an epidermal nevus. The nature of the phosphaturic factor(s) is not well understood, but elevated levels of circulating FGF-23 were recently reported in one patient with hypophosphatemic rickets. The authors suggest that serum FGF-23 measurement be included in the workup of this kind of rickets because there is growing evidence that in these situations the epidermal nevi produce a phosphaturic factor.

Focal fibrocartilaginous dysplasia is a rare benign entity, previously described as a factor responsible for causing tibia vara at the walking age. We report here the case of a child with tibia valga due to focal fibrocartilaginous dysplasia of the lateral part of the proximal tibia. To our knowledge, this is the first observation of a lesion located in the lateral proximal tibia. Clinical, radiographic and magnetic resonance imaging surveillance was performed. Spontaneous resolution of the lesion with correction of the angular deformity did occur.