RESUMEN
Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome (Hay-Wells syndrome, MIM #106220) is a rare autosomal dominant ectodermal dysplasia syndrome. It is due to mutations in the TP63 gene, known to be a regulatory gene with many downstream gene targets. TP63 is important in the differentiation and proliferation of the epidermis, as well as many other processes including limb and facial development. It is also known that mutations in TP63 lead to skin erosions. These erosions, especially on the scalp, are defining features of AEC syndrome and cause significant morbidity and mortality in these patients. It was this fact that led to the 2003 AEC Skin Erosion Workshop. That conference laid the groundwork for the International Research Symposium for AEC Syndrome held at Texas Children's Hospital in 2006. The conference brought together the largest cohort of individuals with AEC syndrome, along with a multitude of physicians and scientists. The overarching goals were to define the clinical and pathologic findings for improved diagnostic criteria, to obtain tissue samples for further study and to define future research directions. The symposium was successful in accomplishing these aims as detailed in this conference report. Following our report, we also present 11 manuscripts within this special section that outline the collective clinical, pathologic, and mutational data from 18 individuals enrolled in the concurrent Baylor College of Medicine IRB-approved protocol: Characterization of AEC syndrome. These collaborative findings will hopefully provide a stepping-stone to future translational projects of TP63 and TP63-related syndromes.
Asunto(s)
Labio Leporino , Fisura del Paladar , Displasia Ectodérmica , Párpados/anomalías , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Anomalías Múltiples/fisiopatología , Animales , Niño , Preescolar , Labio Leporino/diagnóstico , Labio Leporino/genética , Labio Leporino/fisiopatología , Fisura del Paladar/diagnóstico , Fisura del Paladar/genética , Fisura del Paladar/fisiopatología , Displasia Ectodérmica/diagnóstico , Displasia Ectodérmica/genética , Displasia Ectodérmica/fisiopatología , Humanos , Lactante , Recién Nacido , Mutación , Síndrome , Transactivadores/genética , Factores de Transcripción , Proteínas Supresoras de Tumor/genéticaRESUMEN
PURPOSE OF REVIEW: This article reviews the disorders of patterned dyspigmentation and discusses the pathogenesis of the pigmentary changes. RECENT FINDINGS: A range of cytogenetic abnormalities has been detected in patterned pigmentary disease. This molecular heterogeneity correlates with the wide spectrum of clinical phenotypes observed. Many of the molecular defects overlap with genes known to play a role in pigmentation. Our understanding of the underlying genetic mechanisms for these mosaic conditions is evolving with advances in technology and dissection of the molecular pathways involved in melanocyte biology. SUMMARY: The causal heterogeneity of patterned dyspigmentation promises to reveal clues about the differentiation, function, and control of melanocytes in embryonic and postnatal development.