Tracheal agenesis revisited: analysis of associated anomalies

Abstract

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. Am. J. Med. Genet. 82:415–422, 1999. © 1999 Wiley-Liss, Inc.