Neonatal Diagnosis of Alveolar Capillary Dysplasia via Rapid Genomic Sequencing: A New Gold Standard?

Classic alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare congenital lung disorder presenting in the early neonatal period with refractory hypoxemic respiratory failure and pulmonary hypertension. No curative treatment is currently available. Although definitive diagnosis is obtained by histology, lung biopsy is often challenging in unstable, critically ill neonates. Molecular diagnosis has been achieved with chromosomal microarray and targeted gene sequencing; however, each of these modalities can be limited by turnaround time, coverage of the genome, and inability to detect all pathogenic variant types for ACDMPV. We present a case of ACDMPV diagnosed via rapid genome sequencing and posit that rapid genomic sequencing, including both rapid exome and genome sequencing, has an expanding role in severe neonatal respiratory failure as a comprehensive and noninvasive approach to timely diagnosis.