Unilateral Lung Agenesis and Left Isomerism in a Neonate: A Case Report of Multi-system Anomalies

Unilateral agenesis of the lung (UAL) is a rare congenital anomaly resulting from the failed development of the lung bud between weeks three and seven of gestation. It is frequently associated with anomalies involving the cardiovascular, gastrointestinal, and skeletal systems. We describe a full-term male neonate who presented with severe respiratory distress and was found to have complete agenesis of the left lung, bronchus, and pulmonary artery and vein. Additional findings included polysplenia, a midline liver, leftward gallbladder, bifid right thumb, and congenital heart defects, raising concern for an underlying laterality defect. Although heterotaxy syndrome was not formally diagnosed, the constellation of findings is most consistent with left isomerism. Trio-based exome sequencing was negative for pathogenic or likely pathogenic variants, and variants of uncertain significance were not reported. The presence of a bifid thumb, not typically associated with heterotaxy, suggests a broader developmental disruption. Based on established roles in left-right axis patterning, pulmonary morphogenesis, and limb development, the Sonic hedgehog signaling pathway is proposed as a potential contributor. While speculative, this hypothesis provides a developmental framework for the observed anomalies. Early identification of such patterns may aid in diagnosis, prognostication, and coordination of multidisciplinary care. Further research is needed to clarify the embryologic and genetic underpinnings of these rare and complex presentations.