Evans J A, Greenberg C R, Erdile L
Department of Human Genetics, University of Manitoba and Children's Hospital, Winnipeg, Canada.
Am J Med Genet. 1999 Feb 19;82(5):415-22.
We describe five new cases of tracheal agenesis and report on epidemiological and numerical analyses of nearly 100 such cases with multiple congenital anomalies. Malformations seen with tracheal agenesis form patterns which overlap with, but are distinct from, VACTERL association. They have a high frequency of other lower respiratory tract anomalies; e.g., laryngeal atresia and lung lobation defects, and complex heart anomalies, but fewer anal and vertebral malformations. Cluster analysis of the malformations in 86 patients identified four consistent groups. Anomalies in the first group were primarily restricted to the trachea, larynx, and cardiovascular system. In the second group, the patients had more severe cardiac defects, and lung lobation anomalies, while in the third they had a caudal component in addition to thoracic abnormalities, with anal and renal anomalies being common. Each of these groups showed a male excess and may represent increasingly severe perturbations in development fields encompassing the developing respiratory tract. Although the nature of the causative insult is unknown and probably heterogenous, one underlying pathogenetic mechanism may be abnormal epithelial-mesenchymal interactions. Patients in the fourth group also had multisystem involvement with a high incidence of aberrant vessels, complex cardiac malformations, lung lobation defects, and anomalies of other foregut derivatives. The sex ratio in this group was normal and such cases could represent a disturbance in the primary development field during blastogenesis with secondary vascular disruptions. Complete tracheal agenesis is a lethal anomaly. However, segmental forms may be correctable and, in this group of infants, the nature of associated anomalies may well determine long-term prognosis.
我们描述了5例气管发育不全的新病例，并报告了近100例伴有多种先天性畸形的此类病例的流行病学和数值分析。气管发育不全时出现的畸形形成的模式与VACTERL综合征重叠，但又有所不同。它们常伴有其他下呼吸道畸形，如喉闭锁和肺叶发育缺陷，以及复杂的心脏畸形，但肛门和脊柱畸形较少。对86例患者的畸形进行聚类分析，确定了4个一致的组。第一组的畸形主要局限于气管、喉和心血管系统。第二组患者有更严重的心脏缺陷和肺叶异常，而第三组除了胸部异常外，还有尾部成分，肛门和肾脏异常较为常见。每组均以男性居多，可能代表了发育中的呼吸道所涉及的发育领域中越来越严重的干扰。尽管致病损伤的性质尚不清楚且可能是异质性的，但一种潜在的致病机制可能是上皮-间充质相互作用异常。第四组患者也有多系统受累，异常血管、复杂心脏畸形、肺叶发育缺陷及其他前肠衍生物异常的发生率较高。该组的性别比例正常，此类病例可能代表了胚胎形成期初级发育领域的紊乱以及继发性血管破坏。完全性气管发育不全是一种致命的畸形。然而，节段性形式可能是可矫正的，在这组婴儿中，相关畸形的性质很可能决定长期预后。
