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Peer-reviewedCC BY 4.0Frontiers in Pediatrics

Case Report: Familial TBX4-related developmental lung disease: two siblings with fatal neonatal respiratory failure

  • Ranga Prasanth Thiruvenkataramani1,2
  • Tarek Mohamed1,2
  • Mary v Pugmire1
  • Said A. Omar1,2
  1. 1Division of Neonatology, Department of Pediatrics, University of Michigan Health-Sparrow, Lansing, MI, United States
  2. 2Division of Neonatology, Department of Pediatrics and Human Development, Michigan State University, East Lansing, MI, United States
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Abstract

Background: T-box transcription factor 4 (TBX4) is a critical regulator of lung and pulmonary vascular development. Pathogenic TBX4 variants are associated with developmental lung disease, pulmonary hypertension, and neonatal respiratory failure.

Case presentation: We report two siblings with lethal neonatal respiratory failure. The first, a term female infant, died at 11 h of life, and her late-preterm male sibling died at 9 h despite maximal intensive care. Both developed severe hypoxemia and pulmonary hypertension. Autopsy demonstrated marked pulmonary hypoplasia. Whole-exome sequencing identified a novel heterozygous TBX4 variant, c.741G>C (p.Lys247Asn), inherited from their unaffected father. Preimplantation genetic testing detected the variant in seven of 10 embryos.

Conclusion: These cases expand the spectrum of TBX4-associated developmental lung disease and support consideration of TBX4 testing in neonates with unexplained respiratory failure and pulmonary hypertension.

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Cite

BibTeXRIS
BibTeX
@article{thiruvenkataramani2026case,
  title = {{Case Report: Familial TBX4-related developmental lung disease: two siblings with fatal neonatal respiratory failure}},
  author = {Ranga Prasanth Thiruvenkataramani and Tarek Mohamed and Mary v Pugmire and Said A. Omar},
  journal = {Frontiers in Pediatrics},
  year = {2026},
  month = oct,
  doi = {10.3389/fped.2026.1816836},
  url = {https://doi.org/10.3389/fped.2026.1816836},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Case Report: Familial TBX4-related developmental lung disease: two siblings with fatal neonatal respiratory failure
AU  - Ranga Prasanth Thiruvenkataramani
AU  - Tarek Mohamed
AU  - Mary v Pugmire
AU  - Said A. Omar
PY  - 2026
DA  - 2026/10/22
JO  - Frontiers in Pediatrics
DO  - 10.3389/fped.2026.1816836
UR  - https://doi.org/10.3389/fped.2026.1816836
AB  - Background: T-box transcription factor 4 (TBX4) is a critical regulator of lung and pulmonary vascular development. Pathogenic TBX4 variants are associated with developmental lung disease, pulmonary hypertension, and neonatal respiratory failure.  Case presentation: We report two siblings with lethal neonatal respiratory failure. The first, a term female infant, died at 11 h of life, and her late-preterm male sibling died at 9 h despite maximal intensive care. Both developed severe hypoxemia and pulmonary hypertension. Autopsy demonstrated marked pulmonary hypoplasia. Whole-exome sequencing identified a novel heterozygous TBX4 variant, c.741G>C (p.Lys247Asn), inherited from their unaffected father. Preimplantation genetic testing detected the variant in seven of 10 embryos.  Conclusion: These cases expand the spectrum of TBX4-associated developmental lung disease and support consideration of TBX4 testing in neonates with unexplained respiratory failure and pulmonary hypertension.
SN  - 2296-2360
ER  -