Genotype-phenotype variations in PURA syndrome: Asian and non-Asian perspectives from a systematic review

The focus of this study was a comparison of the phenotypical and genotypical differences in PURA syndrome among Asian and non-Asian patients. A retrospective cohort study was performed in a single medical center from January 2014 to May 2025 on patients carrying causative genes for PURA syndrome. A systematic search in PubMed, MEDLINE, Web of Science, and Embase covering the period from January 2014 to May 2025 was conducted. Individuals with PURA syndrome were collected and categorized into Asian and non-Asian groups for analysis. Clinical characteristics, imaging findings, and developmental outcomes were compared between the two groups using Chi-squared or Fisher's exact tests, with a p < 0.05 considered statistically significant.

Of 200 individuals enrolled, 44 were Asian and 156 were non-Asian. 80% or more of individuals with PURA syndrome in both groups shared common clinical features of hypotonia and feeding difficulties during the neonatal period. In terms of neurologic symptoms, there were significantly higher rates of pathological startle response (p < 0.01), and lower rates of epilepsy (p < 0.01) and movement disorders (p = 0.035) among Asian populations. For extra-neurologic symptoms, Asian populations showed a higher incidence of cardiac (p = 0.013) and urogenital abnormalities (p < 0.01), with statistical significance. A single patient in the cohort study exhibited second-degree atrioventricular block, which required pacemaker placement. Highly heterogeneous variants were identified with 106 causative variants in 200 individuals, including a novel causative variant, c.42_57del (p.Leu15fs), from our cohort. All individuals with PURA syndrome displayed evident psychomotor impairment during follow-up.

PURA syndrome exhibits high phenotypic and genotypic heterogeneity. Increased pathological startle response, reduced epilepsy and movement disorders, and higher rates of cardiac and urogenital abnormalities were observed in the Asian group. Cardiac conduction disorder may prove fatal without timely intervention.