Variant Class-Specific Phenotypes and Outcomes in Pediatric TBX4-Associated Pulmonary Hypertension.

TBX4

CNV encompassing TBX4 or TBX4 single nucleotide variant; predominantly lung growth abnormalities on histology, with variable pulmonary vascular remodelling

This retrospective cohort from a national paediatric pulmonary hypertension service (2001-2025) describes 21 children with TBX4-associated pulmonary hypertension carrying either a CNV encompassing TBX4 (n = 10) or a single nucleotide variant (SNV, n = 11). Children in the CNV group were referred younger and more often had prolonged oxygen dependence from birth, more severe lung disease, cyanosis, congenital heart disease, neurodevelopmental disorders and deafness, whereas those in the SNV group were less likely to have any lung disease. Twenty of 21 children (95%) received long-term pulmonary vasodilator therapy, and the 12 treatment-naive children had stable or improved functional class on initiation. Over a median follow-up of 7.1 years, transplant- or Potts shunt-free survival was 100% at 1 year and 94.4% at 5 years, and worse in the CNV group (log-rank p < 0.05).

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The CNV/SNV distinction provides a stratification criterion available as soon as the genetic result is known, useful to anticipate multisystem involvement and plan neurodevelopmental follow-up. Group sizes (10 vs 11) are small for multiple comparisons, and these differences need confirmation. One may wonder whether neighbouring genes included in the CNVs contribute to the broader phenotype, a question the abstract does not address.

Analysis by Dr Thibaut Benquey