Lymphangiectasia, Pulmonary, Congenital

Clinical Features

Frank and Piper (1959) described 2 unrelated infants with congenital pulmonary cystic lymphangiectasis. One was stillborn and the other lived only about 2 hours. In 1 patient there were similar lesions in the heart, pancreas, kidneys, and mesentery.

Scott-Emuakpor et al. (1981) described the disorder in 2 sisters who showed acute respiratory distress soon after birth and died in the neonatal period. Changes at autopsy were limited to the lungs.

Moerman et al. (1993) reported on 7 perinatal autopsy cases of primary congenital pulmonary lymphangiectasis with bilateral chylothorax. They demonstrated that primary CPL is often complicated by chylous pleural effusions with ensuing pulmonary hypoplasia. Conversely, CPL appears to be a constant pathologic finding in spontaneous congenital chylothorax. These observations indicated a common pathogenesis for the 2 disorders. The authors suggested that the basic defect was not an intrinsic lung abnormality, but a developmental error of the lymphatic system resulting in a pulmonary lymphatic obstruction sequence.

Njolstad et al. (1998) reported 3 sibs with nonimmune hydrops fetalis (236750), 2 of whom had histologic evidence of congenital pulmonary lymphangiectasia. One infant died at age 9 hours and another died in utero. Postmortem findings included subcutaneous edema, ascites, hydrothorax, and pleural effusions. The surviving child had frequent upper airway infections with simultaneously increasing edema of the arms and face. She had normal neurologic development. Njolstad et al. (1998) concluded that the nonimmune hydrops fetalis was secondary to primary pulmonary lymphangiectasia, and suggested an underlying genetic cause in this family.

Jacquemont et al. (2000) reported 3 French sibs and an unrelated girl with CPL. Nonimmune hydrops fetalis was observed in 3 patients, and was fatal in 1. Other variable prenatal findings included polyhydramnios and chylothorax. The main clinical features were facial and lower limb edema, episodic lymphangitis, and pleural effusions. One patient also had bilateral chylothorax. Chest radiographs showed chronic pleural effusions, pachypleuritis, and interstitial markings. Pulmonary biopsy of 1 patient showed signs of bronchodysplasia and lymph vessel ectasia. Other common features included mild growth retardation, hypertelorism, palpebral edema, flat nasal bridge, diffuse bone demineralization, and normal intelligence. Although histologic diagnosis of pulmonary lymphangiectasia had been noted by Njolstad et al. (1998) to be uncertain, Jacquemont et al. (2000) stated that chylothorax, chronic pleural effusions, and pleural membrane thickening were consistent with pulmonary lymphangiectasia, especially in the presence of normal cardiac findings. Jacquemont et al. (2000) noted the resemblance to Hennekam syndrome (235510), but concluded that their cases and the cases reported by Njolstad et al. (1998) represented a distinct nosologic entity.

Stevenson et al. (2006) reported 2 sibs with congenital nonimmune hydrops, pleural effusions, and chylothorax. One sib had histologically confirmed pulmonary lymphangiectasia. Both sibs died in the neonatal period. Stevenson et al. (2006) suggested that disordered lymphatic drainage was the basic defect leading to a secondary condition of CPL.

Inheritance

Moerman et al. (1993) concluded that the cause of CPL is heterogeneous. Most cases are apparently sporadic occurrences. They reported the second instance of CPL in sibs. Thus, some cases may be genetically determined with autosomal recessive inheritance. CPL may also be part of a multiple congenital anomalies (MCA) syndrome, such as Noonan syndrome (163950), Turner syndrome, and Down syndrome.