Trainor Paul A, Richtsmeier Joan T
Stowers Institute for Medical Research, Kansas City, Missouri.
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas.
Am J Med Genet A. 2015 Jul;167(7):1451-4. doi: 10.1002/ajmg.a.37065. Epub 2015 Mar 28.
Craniofacial anomalies are among the most common human birth defects and have considerable functional, aesthetic, and social consequences. The early developmental origin as well as the anatomical complexity of the head and face render these tissues prone to genetic and environmental insult. The establishment of craniofacial clinics offering comprehensive care for craniofacial patients at a single site together with international research networks focused on the origins and treatment of craniofacial disorders has led to tremendous advances in our understanding of the etiology and pathogenesis of congenital craniofacial anomalies. However, the genetic, environmental, and developmental sources of many craniofacial disorders remain unknown. To overcome this problem and further advance craniofacial research, we must recognize current challenges in the field and establish priority areas for study. We still need (i) a deeper understanding of variation during normal development and within the context of any disorder, (ii) improved genotyping and phenotyping and understanding of the impact of epigenetics, (iii) continued development of animal models and functional analyses of genes and variants, and (iv) integration of patient derived cells and tissues together with 3D printing and quantitative assessment of surgical outcomes for improved practice. Only with fundamental advances in each of these areas will we be able to meet the challenge of translating potential therapeutic and preventative approaches into clinical solutions and reduce the financial and emotional burden of craniofacial anomalies.
颅面畸形是最常见的人类出生缺陷之一,会产生相当大的功能、美学和社会影响。头部和面部的早期发育起源以及解剖学复杂性使这些组织容易受到遗传和环境损伤。颅面诊所的建立为颅面患者在单一地点提供全面护理,同时国际研究网络专注于颅面疾病的起源和治疗,这使得我们对先天性颅面畸形的病因和发病机制的理解有了巨大进展。然而,许多颅面疾病的遗传、环境和发育根源仍然未知。为了克服这一问题并进一步推进颅面研究,我们必须认识到该领域当前的挑战,并确定优先研究领域。我们仍然需要:(i)更深入地了解正常发育过程中的变异以及在任何疾病背景下的变异;(ii)改进基因分型和表型分析,并了解表观遗传学的影响;(iii)持续开发动物模型以及对基因和变异进行功能分析;(iv)整合患者来源的细胞和组织,以及3D打印和手术结果的定量评估,以改善临床实践。只有在这些领域都取得根本性进展,我们才能应对将潜在治疗和预防方法转化为临床解决方案的挑战,并减轻颅面畸形带来的经济和情感负担。