Clinical and Genetic Characterization of Two Colombian Patients with PURA-Related Neurodevelopmental Disorder: Expanding the Latin American Phenotypic Spectrum

PURA-related neurodevelopmental disorder (PURA-NDD) is a rare monogenic condition characterized by neonatal hypotonia, developmental delay, epilepsy, and variable multisystem involvement. Data from Latin America remains limited, limiting recognition of the disorder in underrepresented populations. We report two unrelated Colombian patients with neonatal onset hypotonia in whom routine metabolic studies, neuroimaging, and electrophysiological evaluation were initially non-diagnostic. Trio-based whole-exome sequencing identified de novo PURA variants in both individuals: a missense variant, c.221A > G (p.Tyr74Cys), affecting the PUR-I domain, and a truncating variant, c.733C > T (p.Arg245*), located in the PUR-III/C-terminal region. Although both patients shared profound hypotonia and global developmental impairment, their clinical trajectories differed. The first patient developed epilepsy, severe intellectual disability, autism spectrum disorder, and persistent motor incoordination without major respiratory compromise. The second patient showed marked feeding and respiratory involvement, including obstructive sleep apnea requiring nocturnal oxygen, but remained seizure-free at last follow-up. Comparison with previously reported Colombian and international cases further illustrates the broad phenotypic variability of PURA-NDD, even among variants affecting highly conserved functional domains. These observations expand the molecular and phenotypic spectrum of PURA-NDD in Latin America and support the early use of trio-based genomic testing in infants and children with unexplained neonatal hypotonia and developmental delay.