Case Report: CTNNB1 Mutation Presenting with refractory Neonatal Pulmonary Hypertension

β-catenin is a key component of the canonical Wnt signaling pathway. Germline mutations in the CTNNB1 gene, which encodes β-catenin, are linked to a spectrum of neurodevelopmental and physical abnormalities. These include Familial exudative vitreoretinopathy (FEVR), characterized by peripheral retinal avascularity, neovascularization, and fibrosis. Neurodevelopmental manifestations commonly include delayed psychomotor development, truncal hypotonia, and progressive spasticity. Limb malformation and cardiac abnormalities have also been reported. While vascular dysfunction underlies the retinal phenotype and the Wnt/β-catenin pathway is critical for vascular development, other vascular abnormalities-particularly pulmonary hypertension (PH), have not been previously reported. We report a term neonate presenting with severe, refractory PH, bilateral oligodactyly, lower limb spasticity, and retinal abnormalities. Trio whole-genome sequencing identified a novel de novo frameshift variant in CTNNB1 (c.2234del, p.Gly745Valfs*43). The patient succumbed during the neonatal period. This early diagnosis expands the phenotypic spectrum of CTNNB1 mutations to include PH, which may be underreported due to early mortality. It also provides insights into CTNNB1's role in pulmonary vascular development and highlights potential therapeutic targets.