Abstract
<title>Abstract</title> <p> <bold>Objective</bold> To summarize the clinical phenotype, genetic features, and key points of diagnosis and treatment of Rubinstein-Taybi syndrome (RSTS), so as to improve the level of early recognition and precise diagnosis of this disease. <bold>Methods</bold> The clinical data, imaging findings, echocardiographic results, genetic testing results, and intellectual development assessments of children diagnosed with RSTS in our center from January 2020 to April 2026 were retrospectively analyzed and summarized with relevant domestic and international literature. <bold>Results</bold> Five children were enrolled, including 3 males and 2 females; the age at first visit ranged from 20 days to 13 years and 4 months. All children presented with global developmental delay/intellectual disability, characteristic craniofacial features (e.g., hypertelorism, downward-slanting palpebral fissures, small auricles), and broad thumbs/stubby fingers (thumb width significantly larger than the ipsilateral index finger, with short and thick phalanges). Four cases had congenital heart disease, 2 had hypertrichosis, 2 had hypotonia, 1 had vertebral malformation, and 1 had corpus callosum dysplasia. Heterozygous pathogenic variants in the CREBBP gene were detected in all cases: 2 missense variants (c.5357G > A, c.4014G > C), 2 nonsense variants (c.528C > A, c.223C > T), and 1 frameshift deletion variant (c.3050_3056del). Three variants were de novo, and 1 was maternally inherited (the mother was a carrier of the variant without obvious clinical phenotype). Intellectual assessments showed moderate to severe developmental delay in all cases, with language delay more severe than motor delay. <bold>Conclusion</bold> The core phenotypes of RSTS include neurodevelopmental disorders, characteristic craniofacial abnormalities, broad thumbs/toes deformity, and multisystem structural malformations. Hemivertebra malformation in this cohort is a novel clinical phenotype. Maternal inheritance is rare, highlighting the need for enhanced pedigree genetic analysis and recurrence risk prediction. Early genetic diagnosis combined with multidisciplinary holistic management can improve the prognosis of affected children. </p>