Clinical and Genetic Analysis of a Chinese Patient Carrying a Novel POGZ Variant Associated with White-Sutton Syndrome

Background: White-Sutton Syndrome (WSS) is a rare autosomal dominant neurodevelopmental disorder caused by pathogenic variants in the POGZ gene, which is essential for chromatin remodeling and neuronal development. Because of its broad phenotypic heterogeneity and lack of disease-specific features, early diagnosis and management remain challenging. Timely genetic testing can significantly aid in early diagnosis and intervention, improving patient outcomes. Objective: To describe the clinical and genetic findings of a Chinese pediatric patient with a novel POGZ mutation, summarize the diagnostic approach, and underscore the importance of early genetic testing and multidisciplinary management for the diagnosis and management of WSS. Method: A 4-month-old male infant presented with developmental delay and abnormal liver function. Comprehensive clinical, imaging, auditory, and ophthalmologic evaluations were performed. Whole-genome sequencing and Sanger validation were conducted, followed by multidisciplinary management including nutritional therapy and early rehabilitation. Result: The patient exhibited microcephaly, hypotonia, distinctive facial dysmorphism, auditory impairment, and retinitis pigmentosa. Brain MRI revealed hypoplasia of the corpus callosum. A novel heterozygous frameshift mutation c.2699_2700dup (p.Leu901TyrfsTer2) in POGZ was identified and classified as pathogenic according to ACMG criteria (PVS1 + PS2 + PM2 + PP4). The variant was not reported in existing genetic databases, representing a novel pathogenic mutation expanding the POGZ mutational spectrum. Despite multidisciplinary rehabilitation, neurodevelopmental progress remained limited. Conclusion: This report documents the first Chinese case of White-Sutton Syndrome caused by a novel POGZ frameshift mutation, emphasizing the importance of early genetic testing for accurate diagnosis and timely intervention. Genetic diagnosis combined with personalized rehabilitation may improve long-term neurodevelopmental outcomes for patients with WSS. This case study expands the mutation spectrum of the POGZ gene and provides valuable reference for the diagnosis, treatment, prognosis assessment, and genetic counseling of WSS patients.