Pulmonary agenesis is a rare developmental condition in which there is complete absence or severe hypoplasia of one or both lungs (Oyamada et al., 1953; Valle, 1955; Booth and Berry, 1967; Borja et al., 1970; Yaghmai, 1970; Costas et al., 1977; Boxer et al., 1978; McCormick and Kuhns, 1979; Shenoy et al., 1979; Mygind and Paulsen, 1980). Although quite rare, it was initially recognized by dePozzi in 1673 (Skandalakis and Gray, 1994). Munchmeyer was the first to diagnose unilateral agenesis of the lung clinically in 1885 (Ferguson and Neuhauser, 1944). There have since been more than 200 cases of unilateral agenesis of the lung reported. However, only 14 cases have been reported of bilateral agenesis of the lung (Allen and Affelbach, 1925; Tuynman and Gardner, 1952; Claireaux and Ferreira, 1957; Devi and More, 1966; Ostor et al., 1978; Faro et al., 1979; Diaz et al., 1989; Engellenner et al., 1989). In some cases, bilateral pulmonary agenesis was an isolated finding. In other cases, pulmonary agenesis was found in association with other anomalies in the gastrointestinal, genitourinary, and ocular systems (Tuynman and Gardner, 1952; Claireaux and Ferreira, 1957; Devi and More, 1966; Ostor et al., 1978).

A number of theories have been advanced to explain the pathogenesis of lung aplasia. Lung aplasia has been observed in experimental animals fed a diet deficient in vitamin A (Warkany et al., 1948). Some authors have suggested that there may be a vascular cause of pulmonary agenesis, similar to that invoked for intestinal atresia (Louw, 1959). Other authors have suggested a genetic cause for the pulmonary agenesis. Booth and McKenzie and their colleagues linked unilateral pulmonary agenesis to ipsilateral facial and jaw abnormalities, an association noted more recently by several authors (McKenzie and Craig, 1955; Booth and Berry, 1967; Kenawi and Dickson, 1976; Maymon et al., 2001; Dorchy, 2004; Priolo et al., 2004). The gene involved may have a variable expressivity and penetrance. However, the actual cause of this type of pulmonary agenesis remains obscure.

Bilateral agenesis of the lung is incompatible with life and, fortunately, is exceedingly rare (Engellenner et al., 1989). Unilateral agenesis occurs approximately 25 times more commonly, and it may be compatible with a normal life (Booth and Berry, 1967; Maltz and Nadas, 1968). Maymon et al. (2001) proposed a classification for the degree of underdevelopment of the lung that has been adopted by many authors. In Class I, there is agenesis of the lung or total absence of the bronchus and lung. In Class II, there is aplasia in which there is a rudimentary bronchus without lung tissue. In Class III hypoplasia there is bronchial hypoplasia and a variably reduced amount of lung tissue present. This classification scheme is most appropriately referred to as agenesis and hypoplasia, with Class I and II representing cases of agenesis, and Class III representing cases of hypoplasia.

Unilateral pulmonary agenesis is associated with a broad range of anomalies of other organ systems. The most common cardiac defect associated with unilateral agenesis is patent ductus arteriosus (PDA). Although PDA is a common neonatal finding, it may or may not relate directly to the nature of the underlying cause of the pulmonary agenesis. Another common finding is anomalous pulmonary venous drainage, either to the azygos vein or to a persistent left superior vena cava. Other cardiovascular anomalies that have been reported include left pulmonary artery posterior to the left bronchus, aorta anterior to the trachea and compressing it with the left pulmonary artery posterior to the trachea, an anomalous pulmonary venous drainage of the left lung to the right atrium, and four pulmonary veins on the right side. In addition, atrial and ventricular septal defects have been reported in association with pulmonary agenesis.

Although tracheoesophageal anomalies may accompany unilateral pulmonary agenesis, only 14 cases have been recorded thus far, one of which was tracheoesophageal fistula (Kitagawa et al., 1995; Steadland et al., 1995; Vittraino et al., 2003). Other gastrointestinal anomalies associated with pulmonary agenesis include duodenal atresia, annular pancreas, malrotation, Meckel diverticulum, and imperforate anus. Barium contrast studies may demonstrate deviation of the esophagus to the agenetic side, particularly when the right lung is absent. Occasionally the diaphragm may be deficient on either the ipsilateral or contralateral side, allowing eventration of the abdominal viscera. However, this diaphragmatic anomaly is more commonly seen accompanying pulmonary hypoplasia than agenesis.

The most common spinal abnormality seen in association with pulmonary agenesis is hemivertebrae (see Chapter 88). This can be seen in both agenesis of the lung and hypoplasia of the lung. The resulting scoliosis may be quite severe and produce an additional handicap in the child already suffering from recurrent respiratory infection. Such scoliosis may also be due to a rudimentary rim of lung tissue on the affected side. An abnormality of the spine or ribs in the cervical or thoracic regions may be attended by a more prominent scapula on the affected side.

In at least six cases, there have been associated facial or jaw abnormalities ipsilateral to the side of the pulmonary agenesis or hypoplasia (David et al., 1996; Cunningham and Mann, 1997). These abnormalities have included hemifacial microsomia, deformed left external ear, seventh nerve paralysis, small deformed right ear without a patent external auditory canal, facial asymmetry, torticollis, and unilateral mandibulofacial dysostosis (see Chapter 24).

Ipsilateral limb abnormalities have also been observed in many of these cases. These usually involve the upper extremity on the ipsilateral side (Cunningham and Mann, 1997; Aggarwal et al., 2002). While abnormalities of both the ulna and the radius and malformation of the carpus result in a smaller, less powerful hand and arm, the most characteristic abnormalities have been noted in the ipsilateral thumb. These included triphalangia; angulated thumb, in which the middle phalanx is hypoplastic; a preaxial polydactyly; and an abnormal thumb with a short first metacarpal. Some of these digital radial dysplasias fit the pattern of the Holt–Oram syndrome (Holt and Oram, 1960) and the ventriculoradial dysplasia syndrome (Harris and Osborn, 1966). Because of the association of pulmonary agenesis, or vascular anomalies, gastrointestinal anomalies (tracheoesophageal fistula, imperforate anus), vertebral anomalies (fetal vertebrae or hemivertebrae), urogenital anomalies (renal agenesis, horseshoe kidney, hemiuterus), radial ray anomalies, and ipsilateral craniofacial anomalies (microtic facial asymmetry and hemifacial microsomia) have suggested that pulmonary agenesis should be considered part of the VACTERL Association (Knowles et al., 1988; David et al., 1996; Cunningham and Mann, 1997). At least 13 cases of unilateral pulmonary agenesis have now been reported as part of the VACTERL Association (Knowles et al., 1988; David et al., 1996; Bromley and Benacerraf, 1997; Cunningham and Mann, 1997; Chen et al., 2003).

The incidence of agenesis, either unilateral or bilateral, is uncertain. Based on a report of four cases among 114,569 hospital admissions Borja et al. (1970) suggested a prevalence of 0.0034%. During a 6-year period, four other patients were noted with unilateral agenesis among 41,403 admissions to the King Feisel Specialist Hospital and Research Center, which would represent a prevalence of 0.0097% or approximately 1 in 10,000 admissions, or 0.67% of the 596 patients who underwent cardiac catherization at that center (Mardini and Nyhan, 1985). Agenesis of the right lung and agenesis of the left lung are about equally common. Females are affected slightly more commonly than males, and the condition may be inherited (Schechter, 1968; Mardini and Nyhan, 1985).

There is no estimate of the prenatal incidence of pulmonary aplasia; however, Schechter (1968) has estimated an incidence of 1 in 15,000 based on autopsies. Both lungs are affected with equal frequency, although patients with left lung aplasia are thought to have a much better prognosis.

The diagnosis of pulmonary agenesis is often made only at the time of autopsy. However, in recent years cases of unilateral pulmonary agenesis have been recognized prenatally (Engellenner et al., 1989; Becker et al., 1993; Yancey and Richards, 1993; Bromley and Benacerraf, 1997; Maymon et al., 2001; Viora et al., 2002; Chen et al., 2003). Sonographically, the mediastinum is shifted toward the affected side and the diaphragm on the ipsilateral side is elevated. Care should be taken to distinguish pulmonary hypoplasia caused by compression from a diaphragmatic hernia or cystic adenomatoid malformation from unilateral agenesis. The sonographic features of unilateral pulmonary agenesis include medial mediastinal shift to the agenetic side and enlarged echogenic lung herniating into the contralateral chest anterior and/or posterior to the mediastinum. There may be associated scoliosis with a curve toward the agenetic side with or without hemivertebrae. Because of the frequency of associated anomalies in pulmonary agenesis affecting other organ systems, a careful sonographic examination should be performed, including scanning of the vertebrae, heart, and limbs and the genitourinary and central nervous systems. There is an association with ipsilateral radial ray defects and hemifacial microsomia. The presence of bilateral facial or radial ray anomalies may be seen in bilateral pulmonary agenesis (Cunningham and Mann, 1997). Renal abnormalities including dysplasia, pelvic kidney, and horseshoe kidney have been reported with unilateral pulmonary agenesis, as has encephalocele (Becker et al., 1993; Cunningham and Mann, 1997; Eroglu et al., 2005). Both polyhydramnios and oligohydramnios have been reported in pulmonary agenesis (Engellenner et al., 1989). In the single case of nonimmune hydrops reported in a fetus with unilateral pulmonary agenesis, it was thought to be due to partial closure of the ductus arteriosus in an otherwise structurally normal heart (Engellenner et al., 1989).