RESUMO
Frontonasal dysplasias are rare congenital malformations of frontonasal process-derived structures, characterized by median cleft, nasal anomalies, widely spaced eyes, and cranium bifidum occultum. Several entities of syndromic frontonasal dysplasia have been described, among which, to date, only a few have identified molecular bases. We clinically ascertained a cohort of 124 individuals referred for frontonasal dysplasia. We identified six individuals with a similar phenotype, including one discordant monozygous twin. Facial features were remarkable by nasal deformity with creased ridge and depressed or absent tip, widely spaced eyes, almond-shaped palpebral fissures, and downturned corners of the mouth. All had apparently normal psychomotor development. In addition, upper limb anomalies, frontonasal encephalocele, corpus callosum agenesis, choanal atresia, and congenital heart defect were observed. We identified five reports in the literature of patients presenting with the same phenotype. Exome sequencing was performed on DNA extracted from blood of two individuals, no candidate gene was identified. In conclusion, we report six novel simplex individuals presenting with a specific frontonasal dysplasia entity associating recognizable facial features, limb and visceral malformations, and apparently normal development. The identification of discordant monozygotic twins supports the hypothesis of a mosaic disorder. Although previous patients have been reported, this is the first series, allowing delineation of a clinical subtype of frontonasal dysplasia, paving the way toward the identification of its molecular etiology.
Assuntos
Anormalidades Múltiplas/genética , Agenesia do Corpo Caloso/diagnóstico , Atresia das Cóanas/diagnóstico , Anormalidades Craniofaciais/diagnóstico , Encefalocele/diagnóstico , Face/anormalidades , Cardiopatias Congênitas/diagnóstico , Agenesia do Corpo Caloso/genética , Atresia das Cóanas/genética , Estudos de Coortes , Anormalidades Craniofaciais/classificação , Anormalidades Craniofaciais/genética , Encefalocele/genética , Encefalocele/patologia , Ossos Faciais/anormalidades , Feminino , Cardiopatias Congênitas/genética , Humanos , Lactente , Masculino , Nariz/anormalidades , Fenótipo , Sequenciamento do ExomaRESUMO
Polyurethane (PU) and doxorubicine loaded-PU nanofiber mats were prepared by the electrospinning technique. The effect of some system and process parameters including flow rate, distance from collector, and concentration of solution on the size and morphology of nanofibers was investigated. The size, morphology and drug content of nanofiber mats were followed by scanning electron microscopy (SEM). FTIR and TGA methods were used for structural and thermal characterization, and DSC was also used for determining the form of drug within nanofiber mat. Doxorubicine release kinetics were studied in two different pHs (4.5 and 7.5) for two drug content and it was observed that there is an inverse correlation between the amounts of drug loaded and released.