Truncating variants in SRCAP outside the Floating-Harbor syndrome (FLHS) locus cause a distinct neurodevelopmental disorder characterized by developmental delay, behavioral problems, and musculoskeletal issues. These individuals exhibit a unique DNA methylation signature that distinguishes them from FLHS, supporting the classification of this condition as a separate entity called non-FLHS SRCAP-related NDD.

None identified.

This study provides valuable insights into the phenotypic and molecular consequences of SRCAP variants outside the FLHS-causing locus, expanding our understanding of this gene's role in neurodevelopmental disorders. The identification of a distinct DNA methylation signature for non-FLHS SRCAP-related NDD is a significant contribution, enhancing diagnostic capabilities. While the small sample size for the distal SRCAP group and the nonspecific clinical features pose limitations, the overall methodology and findings are robust, warranting a rating of 4.