Coexistence of two rare disorders: Cornelia de Lange syndrome and Turner syndrome

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• Título: Coexistence of two rare disorders: Cornelia de Lange syndrome and Turner syndrome
• Autor: Gil-Rodríguez, María Concepción; Baquero Montoya, Carolina; Wierzba, Jolanta; Puisac, Beatriz; Teresa-Rodrigo, María Esperanza; Hernández-Marcos, María; Polucha, Anna; Winnicka, Dorota; Vicente-Gabás, Alicia; Flórez-Gómez, Óscar; Bueno Lozano, Gloria; Limon, Januz; Ramos, Feliciano J.; Pié, Juan
• Publicación original: Introduction to Clinical Methods in Neurological Disorders” (BK041-1-1). Ed: iConcept Press Ltd. 2014
• Descripción física: PDF
• Nota general:
  • Colombia
• Notas de reproducción original: Digitalización realizada por la Biblioteca Virtual del Banco de la República (Colombia)
• Notas:
  • Resumen: Abstract: Cornelia de Lange syndrome (CdLS) is a dominant inherited congenital developmental disorder characterized by facial dysmorphism, growth and cognitive impairment, limb malformations and multiple organ involvement. Mutations in five genes, encoding subunits of the cohesin complex (SMC1A, SMC3, RAD21) and its regulators (NIPBL, HDAC8), are responsible for ~ 70% of CdLS cases. Cohesin complex participates in chromosome segregation, DNA repair mechanisms, gene expression and chromosome conformation. Turner syndrome (TS) affects about one in 2000 live born females and results from complete or partial absence of one of the X chromosomes, frequently accompanied by cell-line mosaicism. Here, we describe a patient with CdLS due to a mutation in the NIPBL gene (c.1445_1448delGAGA, p.(Arg482Asnfs*20)) and mosaic TS (mos 45,X/46,XX karyotype). The patient showed multiple clinical features related to CdLS: craniofacial dysmorphism, pre- and post-natal growth delay, minor musculoskeletal anomalies, congenital heart defects and hirsutism. She also presented severe neurological involvement, including slight hypertonia, learning disabilities, verbal and motor development delay, intellectual impairment and (autistic-like features, aggression, self-injurious behaviour). In addition, the proband was clinically diagnosed with TS because of two typical recognizable features: the peripheral lymphedema and the webbed neck. Molecular characterization showed that the NIPBL mutation was present in the two tissues analyzed from different embryonic origins (peripheral blood lymphocytes from mesoderm and oral mucosa epithelial cells from ectoderm). However, FISH analyses revealed that the percentage of cells with monosomy X was low and tissue-specific. These findings indicate that, ontogenically, the NIPBL mutation may have appeared before the mosaic monosomy X. The coexistence in a patient of two rare disorders raises the issue of whether there is indeed a cause-effect association. In addition, we are forced to investigate the correlation between the genotype (a frameshift NIPBL mutation) and karyotype (mosaic X chromosome aneuploidy), with the patient’s phenotype. Therefore, we compare the clinical signs of each organ system described in our case to the typical clinical features of Cornelia de Lange and Turner syndromes. We conclude that our case seems to show a predominant CdLS phenotype, although additional TS manifestations might appear in adolescence. Besides, the significant neurological involvement reinforces the idea that the brain is the organ most sensitive to cohesin disruption.
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  • Colfuturo
• Idioma: castellano
• Institución origen: Biblioteca Virtual del Banco de la República
• Encabezamiento de materia:
  • CdLS; Turner Syndrome; Mosaic
  • Tecnología; Tecnología / Ciencias médicas Medicina; Tecnología / Ciencias médicas Medicina / Enfermedades