Tracheal agenesis revisited: Analysis of associated anomalies

We describe five new cases of tracheal agenesis and report on epidemiologic al and numerical analyses of nearly 100 such cases with multiple congenital anomalies. Malformations seen with tracheal agenesis form patterns which o verlap with, but are distinct from, VACTERL association. They have a high f requency of other lower respiratory tract anomalies; e.g., laryngeal atresi a and lung lobation defects, and complex heart anomalies, but fewer anal an d vertebral malformations. Cluster analysis of the malformations in 86 pati ents identified four consistent groups. Anomalies in the first group were p rimarily restricted to the trachea, larynx, and cardiovascular system. In t he second group, the patients had more severe cardiac defects, and lung lob ation anomalies, while in the third they had a caudal component in addition to thoracic abnormalities, with anal and renal anomalies being common. Eac h of these groups showed a male excess and may represent increasingly sever e perturbations in development fields encompassing the developing respirato ry tract. Although the nature of the causative insult is unknown and probab ly heterogenous, one underlying pathogenetic mechanism may be abnormal epit helial-mesenchymal interactions. Patients in the fourth group also had mult isystem involvement with a high incidence of aberrant vessels, complex card iac malformations, lung lobation defects, and anomalies of other foregut de rivatives. The sex ratio in this group was normal and such cases could repr esent a disturbance in the primary development field during blastogenesis w ith 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 pr ognosis. (C) 1999 Wiley-Liss, Inc.