# Primary Pulmonary Hypoplasia With Congenital Alveolar Dysplasia Associated With TBX4 Gene Deletion: A Case With Autopsy and Molecular Findings

## TL;DR

A neonate with severe respiratory distress had a rare genetic deletion in TBX4, leading to underdeveloped lungs and alveolar dysplasia.

## Contribution

This case highlights the importance of considering rare genetic deletions like TBX4 haploinsufficiency in diagnosing neonatal pulmonary disorders.

## Key findings

- Autopsy revealed primary pulmonary hypoplasia and congenital alveolar dysplasia in a fatal neonatal case.
- A chromosomal microarray identified a TBX4 gene deletion not detected by standard sequencing panels.
- TBX4 haploinsufficiency is a rare but significant cause of pulmonary developmental disorders.

## Abstract

Acute respiratory distress in a neonate is a potentially critical condition with multiple possible causes. Developmental etiologies are particularly problematic by virtue of being refractory to routine modalities for enhancing ventilation and oxygen exchange. Some genetic causes of neonatal respiratory distress, such as surfactant protein deficiencies and alveolar capillary dysplasia with misalignment of pulmonary veins, are well known, and sequencing panels have been formulated to detect them. We present a case of fatal neonatal respiratory insufficiency in which the autopsy showed primary pulmonary hypoplasia and congenital alveolar dysplasia. A sequencing panel of genes associated with heritable pulmonary disorders gave a normal result; however, a chromosomal microarray identified a heterozygous deletion encompassing the TBX4 gene on chromosome 17. Haploinsufficiency for TBX4 is a known cause of disturbed pulmonary development. This case illustrates why work-up of pulmonary developmental disorders must look beyond standard sequencing panels in some instances, if rare causes of pulmonary maldevelopment such as deletions causing haploinsufficiency are not to be missed.