ABSTRACT
La Aracnodactilia Contractural Congénita (ACC) es una enfermedad del tejido conectivo de herencia autosómica dominante, causada por variantes en el gen FBN2 que codifica la fibrilina-2. Tiene características específicas como contracturas congénitas, oreja con hélice superior arrugada, camptodactilia, pectus carinatum y complicaciones como escoliosis y la cifoescoliosis. Publicamos el caso de una paciente femenina de 19 años con historia de delgadez, velocidad de crecimiento acelerada, talla alta, pérdida de peso, contracturas articulares, hipotonía congénita, pubertad precoz, hábito marfanoide, pectus carinatum y leve aracnodactilia. Se sospecha de enfermedad del colágeno y se solicita secuenciación del exoma completo mediante NGS (del inglés Next Generation Sequencing) + CNVs (del inglés Copy Number Variations) genes relacionados con colagenopatías; se identificó una variante en el gen FBN2 (NM_001999.4): c.4394G>A; p.Cys1465Tyr; estado heterocigoto de significancia clínica probablemente patogénica. La ACC es fenotípicamente similar al síndrome de Marfán y se caracteriza por aracnodactilia, dolicostenomelia, escoliosis, contracturas congénitas múltiples y anomalías de los oídos externos. A diferencia del síndrome de Marfán; no tiene compromiso ocular ni afecta la raíz aórtica. Cuenta con variabilidad fenotípica que le dan la heterogeneidad que pueden interferir y retrasar el proceso diagnóstico y terapéutico específico al solaparse con otras condiciones médicas. Los avances en la medicina y la genómica con la utilización de nuevos métodos diagnósticos han permitido que cada día nos acerquemos más a la medicina 6P (precisión, predicción, prevención, personalizada, participativa con enfoque poblacional) que impacta en el diagnóstico, tratamiento específico, seguimiento, pronóstico y adecuado asesoramiento genético de las enfermedades. (provisto por Infomedic International)
Contractural arachnodactyly congenita (CCA) is an autosomal dominantly inherited connective tissue disease caused by variants in the FBN2 gene encoding fibrillin-2. It has specific features such as congenital contractures, wrinkled upper helix ear, camptodactyly, pectus carinatum and complications such as scoliosis and kyphoscoliosis. We publish the case of a 19-year-old female patient with a history of thinness, accelerated growth velocity, tall stature, weight loss, joint contractures, congenital hypotonia, precocious puberty, marfanoid habitus, pectus carinatum and mild arachnodactyly. Collagen disease was suspected and whole exome sequencing by NGS (Next Generation Sequencing) + CNVs (Copy Number Variations) genes related to collagenopathies was requested; a variant was identified in the FBN2 gene (NM_001999.4): c.4394G>A; p.Cys1465Tyr; heterozygous state of probably pathogenic clinical significance. CCA is phenotypically similar to Marfan syndrome and is characterized by arachnodactyly, dolichostenomelia, scoliosis, multiple congenital contractures, and external ear anomalies. Unlike Marfan syndrome, it has no ocular involvement and does not affect the aortic root. It has phenotypic variability that gives it heterogeneity that can interfere and delay the specific diagnostic and therapeutic process by overlapping with other medical conditions. Advances in medicine and genomics with the use of new diagnostic methods have allowed us to get closer to 6P medicine (precision, prediction, prevention, personalized, participatory with a population approach) that impacts on the diagnosis, specific treatment, follow-up, prognosis and adequate genetic counseling of diseases. (provided by Infomedic International)
ABSTRACT
@#We report a case of a 12-year-old Filipino female with crumpled ears, arachnodactyly, camptodactyly, and congenital joint contractures, consistent with Beals syndrome. Marfan syndrome is a common differential diagnosis, since both are caused by mutations in two homologous genes, namely FBN1 and FBN2. Both syndromes share similar characteristics hence, it is essential to differentiate the two, since Marfan syndrome may develop fatal complications, not encountered in Beals Syndrome. Management of Beals syndrome is mainly supportive including physiotherapy and ophthalmologic and cardiovascular evaluation.
Subject(s)
Marfan SyndromeABSTRACT
Beals syndrome, also known as Beals-Hecht syndrome or congenital contractural arachnodactyly, is a rare, autosomal dominant connective tissue disorder. It is characterized by crumpled ears, arachnodactyly, congenital contractures and scoliosis. A male infant of 37+5 weeks of gestation, and with birth weight of 3170 grams, had features of a long and narrow face, bilateral crumpled inferior helix, prominent antihelix of the ears, bilateral arachnodactyly, clenched position of the hands and flexion contractures of the elbows and knees. The infant had tachypnea and chest retractions shortly after birth, and was diagnosed with transient tachypnea of newborn with pneumothorax. He was subsequently treated with positive pressure ventilation and chest tube insertion. Chromosomal karyotype analysis was normal and screening for Marfan syndrome was negative. Echocardiographic findings were unremarkable. Cranial ultrasonography showed a left lateral ventricle dilatation of 0.5 cm and increase up to 1.2 cm on follow up. Brain MRI showed a progression of dilatation of the left ventricle, and a ventriculo-peritoneal shunt was done at 3 months of age. We present a case of a newborn male with Beals syndrome, accompanied with ventricular dilatation and progression to hydrocephalus that has not been previously reported.
Subject(s)
Humans , Infant , Infant, Newborn , Male , Pregnancy , Arachnodactyly , Birth Weight , Brain , Chest Tubes , Connective Tissue , Contracture , Dilatation , Ear , Elbow , Follow-Up Studies , Hand , Heart Ventricles , Hydrocephalus , Karyotype , Knee , Lateral Ventricles , Marfan Syndrome , Mass Screening , Parturition , Pneumothorax , Positive-Pressure Respiration , Scoliosis , Tachypnea , Thorax , Transient Tachypnea of the Newborn , Ventriculoperitoneal ShuntABSTRACT
Objective:To study the gene expression and aberrant methylation of FBN2 on lung cancer cell lines.Methods:Three lung cancer cell lines HCC366,H1299 and H2195 were cultured.mRNA was analysed by RT-PCR and methylation status was also investigated by methylation specific PCR.The loss of FBN2 expression cell lines were treated with the demethylating agent,5-aza-2'-deoxycytid-ine(5-aza-cdR).Results:The expression of FBN2 was detected in NHBEC and H2195,whereas it was not detected in HCC366 and H1299 which showed aberrant methylation of FBN2.FBN2 expression was restored after treatment with 5-aza-cdR.Conclusion:Methylation and silencing of FBN2 in tumor cells may play an important role in carcinogenesis of lung cancer.