P2.217: Expanding the 3p Duplication Phenotype: A Case of Central Hypoventilation and Immune Dysfunction in a Neonate

Introduction: Chromosome 3p duplication is rare, with only 18 reported cases in the literature. Presentations typically include congenital anomalies, hypotonia, developmental delay, and dysmorphic features. Central respiratory failure has not been previously documented. We report a full-term infant with central hypoventilation due to an inherited unbalanced translocation resulting in 3p duplication and 7q deletion.

Case Description: A full-term male, born via spontaneous vaginal delivery after an uncomplicated pregnancy, exhibited dysmorphic features including micrognathia, widely spaced nipples, micropenis, and a sandal gap. Despite CPAP support at birth, he developed respiratory failure requiring intubation. Surfactant administration was ineffective, and he showed progressive lung opacities with respiratory acidosis. A failed extubation on day of life (DOL) 7 prompted further evaluation. Extensive workup ruled out metabolic disorders, structural anomalies, and infectious causes. Chromosomal microarray revealed an inherited unbalanced translocation involving 3p duplication and 7q deletion (Figure 1), prompting further genetic evaluation. Genome sequencing ruled out additional pathogenic variants, supporting the duplication as the likely cause of central hypoventilation.

On DOL 17, he developed gram-negative sepsis requiring vasopressor support. Despite intensive care, his condition deteriorated with cardiovascular instability and anasarca. After extensive counseling, comfort care was pursued, and he passed away at 6 weeks of age.

Discussion: This case expands the clinical phenotype associated with 3p duplication to include central hypoventilation and immune dysfunction. With other causes of respiratory failure ruled out, the chromosomal duplication is the most likely etiology. Our patient’s persistent respiratory failure, bradycardia, and inability to wean from ventilatory support suggest disruption of central respiratory and autonomic control mechanisms.

Most previously reported cases of 3p duplication involved older children with developmental delay and dysmorphic features, with relatively stable early clinical courses. This contrasts with our patient, who presented with severe neonatal symptoms and rapid clinical deterioration, suggesting that larger duplications may be associated with higher early mortality.

In addition to respiratory dysfunction, our patient developed severe sepsis and multi-organ failure, indicating possible immunologic vulnerability. This multisystem involvement highlights the potential for a broader and more severe phenotype than previously appreciated.

Conclusion: This case highlights the need for genetic evaluation in neonates with unexplained respiratory failure. Given the high mortality of large 3p duplications, further research is needed to define its clinical spectrum and guide management.