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.

Agenesis of the penis is a rare malformation that occurs in otherwise normal males or together with other anomalies. In this article, we document unusual patterns of malformations in four such infants and analyze the nature and incidence of defects in 57 cases by clinical evaluation and numerical classification techniques. Although patients with this condition previously have been divided into groups based on the position of the urethral meatus in relation to the anus (presphincteric, postsphincteric, urethral atresia), our analyses suggest that most cases can be classified into either a severe form (16%) with renal aplasia or dysplasia and other caudal anomalies or a second group (72%) with low mortality and fewer additional malformations. The remaining cases in our group represented unique patterns stemming from a variety of causes, including etretinate embryopathy and the human homologue of the disorganization mutation. Agenesis of the penis occurs as a consequence of single gene disorders, teratogenic effects, or malformation sequences and associations and in unrecognized patterns of anomalies. It thus should be considered a developmental field defect. Its concurrence with scrotal hypoplasia, absent raphe, and anal anomalies implies a major disturbance of the caudal mesoderm. In such cases, severe renal defects are usually seen, and the prognosis is poor. When the patient has a patent urethra and normal scrotum, raphe, and testes, however, penile agenesis may be a localized malformation of the genital tubercle potentially related to penoscrotal transposition, a phylogenetic anomaly that is the normal genital arrangement in male marsupials, rabbits, and certain other mammals. Infants with isolated penile agenesis have generally done well. In the past, many were not treated; however, current recommendations are to use appropriate surgical and endocrine techniques to reassign female gender and enhance sexual and psychosocial functioning, though this approach is the subject of controversy.

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.