There is some debate in the literature about who first recognized the combination of clinical features that, in 1981, were represented in the acronym CHARGE (coloboma-heart defect-atresia of the choanae-retardation-genital and-ear abnormalities) by Pagon, Graham, Zonana, and Yong (1981). The article in this issue by Hefner and Fassi provides a comprehensive discussion of topics related to genetic diagnosis and counseling in CHARGE syndrome. This emphasizes the need for variant interpretation guidelines and functional studies ( Bergman et al., 2012). However, genome-wide screening has also revealed CHD7 variants for which clinical significance is difficult to predict, especially when the a priori chance of finding a pathogenic variant is low. With the introduction of fast and cost-efficient genome-wide variant screening techniques, more individuals with an atypical presentation of the syndrome are being identified, gradually changing the phenotypic spectrum and thus the clinical implications of the diagnosis ( Hale, Niederriter, Green, & Martin, 2016).
#Mild charge syndrome full
The ability to molecularly confirm the diagnosis has enabled a more precise description of the full phenotypic spectrum ( Bergman et al., 2011 Zentner, Layman, Martin, & Scacheri, 2010) and has improved genetic counseling on recurrence risk, recognizing that not all individuals are sporadic ( Jongmans et al., 2008). Basic studies on the function of CHD7 have also contributed to the understanding of this phenotypically complex and highly variable syndrome. Since then, more papers have been published each year on the phenotypic spectrum of the syndrome and its underlying pathogenic mechanisms.
We hope the excitement around innovative research and development in CHARGE syndrome will encourage others to join this effort, and will stimulate other investigators and professionals to engage with individuals diagnosed as having CHARGE syndrome, their families, and their care providers.ĬHD7 (OMIM #214800) was discovered in 2004 as the main gene involved in CHARGE syndrome (OMIM #608892) ( Vissers et al., 2004). In this article, we summarize those advances, highlight opportunities for new discoveries, and encourage readers to explore specific organ systems in more detail in each individual article. Since 2004, when CHD7 was identified as the major causative gene in CHARGE, several animal models (mice, zebrafish, flies, and frog) and cell-based systems have been developed to explore the underlying pathophysiology of this condition. In this special issue of the American Journal of Medical Genetics part C, authors of eleven manuscripts describe specific organ system features of CHARGE syndrome, with a focus on recent developments in diagnosis, etiologies, and treatments. CHARGE syndrome is a multiple congenital anomaly condition caused, in a majority of individuals, by loss of function pathogenic variants in the gene CHD7.
0 kommentar(er)
