New Variant Found in the Bone Morphogenetic Protein Receptor 1B Gene in a Neonate With Trisomy 21

Abstract

We present a case of a 29-week preterm infant delivered by emergency cesarean section due to suspected placental abruption, with a birth weight of 1.17 kg. The APGAR score was 7 at 1 min and 9 at 5 min. The baby was transferred on non-invasive ventilator support to the neonatal intensive care unit (NICU). Physical examination revealed features consistent with Down syndrome. Subsequently, he developed worsening respiratory distress, necessitating intubation and mechanical ventilation, ultimately requiring high-frequency oscillatory ventilation (HFOV). Despite surfactant administration, there was no improvement in the respiratory status. Echocardiography revealed severe pulmonary hypertension. Treatment with nitric oxide and later sildenafil was initiated, but there was limited clinical improvement. After consultation with a pediatric pulmonologist, genetic testing was pursued to investigate the possibility of mutations in surfactant-related genes. The genetic analysis identified a novel missense variant (p.His391Arg) in the bone morphogenetic protein receptor 1B (BMPR1B) NM_001203.3 gene, which has not been previously reported in disease-associated contexts and is not present in large population databases such as the Genome Aggregation Database (gnomAD) and the Greater Middle East (GME) variome database. Unfortunately, despite intensive care efforts, the infant remained critically ill and passed away on day 43 of life. Through this case report, we aim to highlight this novel mutation in the BMPR1B gene for pediatricians and neonatologists worldwide. We also seek to raise awareness about the associated clinical features and the importance of considering such mutations in the differential diagnosis. Furthermore, we advocate for ongoing research to develop improved management strategies that may enhance survival outcomes for infants with similar genetic mutations.

Int J Clin Pediatr. 2024;13(2):60-65
doi: https://doi.org/10.14740/ijcp534