Byers Heather M, Chen Maida, Gelfand Andrew S, Ong Bruce, Jendras Marisa, Glass Ian A
Division of Medical Genetics, Department of Pediatrics, Stanford University, Palo Alto, California.
Department of Pediatrics, University of Washington, Seattle, Washington.
Am J Med Genet A. 2018 Jun;176(6):1398-1404. doi: 10.1002/ajmg.a.38726. Epub 2018 Apr 25.
Congenital central hypoventilation syndrome (CCHS) is a neurocristopathy caused by pathogenic heterozygous variants in the gene paired-like homeobox 2b (PHOX2B). It is characterized by severe infantile alveolar hypoventilation. Individuals may also have diffuse autonomic nervous system dysfunction, Hirschsprung disease and neural crest tumors. We report three individuals with CCHS due to an 8-base pair duplication in PHOX2B; c.691_698dupGGCCCGGG (p.Gly234Alafs*78) with a predominant enteral and neural crest phenotype and a relatively mild respiratory phenotype. The attenuated respiratory phenotype reported here and elsewhere suggests an emergent genotype:phenotype correlation which challenges the current paradigm of invoking mechanical ventilation for all infants diagnosed with CCHS. Best treatment requires careful clinical judgment and ideally the assistance of a care team with expertise in CCHS.
先天性中枢性低通气综合征（CCHS）是一种由成对样同源盒2b（PHOX2B）基因的致病性杂合变异引起的神经嵴病。其特征为严重的婴儿期肺泡低通气。患者还可能出现弥漫性自主神经系统功能障碍、先天性巨结肠病和神经嵴肿瘤。我们报告了3例因PHOX2B基因8个碱基对重复导致的CCHS患者；c.691_698dupGGCCCGGG（p.Gly234Alafs*78），具有主要的肠道和神经嵴表型以及相对较轻的呼吸表型。此处及其他地方报道的减弱的呼吸表型提示了一种新出现的基因型与表型的相关性，这对当前为所有诊断为CCHS的婴儿进行机械通气的范例提出了挑战。最佳治疗需要仔细的临床判断，理想情况下需要有CCHS专业知识的护理团队的协助。
