Genetic Etiology and Neurodevelopmental Outcomes in Children With Craniosynostosis: A 15-Year Single-Center Retrospective Study.
Neurodevelopmental disorders more common in craniosynostosis patients with pathogenic gene variants
Genetic Etiology and Neurodevelopmental Outcomes in Children With Craniosynostosis: A 15-Year Single-Center Retrospective Study.
The traditional distinction between syndromic and nonsyndromic craniosynostosis has guided clinical management, but recent genomic advances suggest these categories represent a continuous spectrum rather than discrete entities.
The authors conducted a retrospective cohort study of 68 consecutive children diagnosed with craniosynostosis at a single tertiary center between January 2011 and November 2025.
including ADHD, neurodevelopmental disorders were far more likely with pathogenic variants
Of 68 patients (40 males, 28 females), 39 (57.4%) underwent genetic testing, with pathogenic or likely pathogenic (P/LP) variants identified in 11 (28.2%; genetic-positive group).
Identified variants involved chromatin modifiers (DNMT3A, NSD1, KMT2A), transcription factors (TCF12, SOX5), a signaling kinase (TAOK1), and a post-transcriptional regulator (TNRC6B); chromosomal microarray analysis additionally revealed pathogenic copy number variants (10q26.13-q26.3 deletion, 16p11.2 duplication, 15q11.2-q13.1 duplication, 2q37 deletion).
Comprehensive genetic testing yielded P/LP variants in 28.2% of tested craniosynostosis patients, revealing diverse molecular etiologies.
Neurodevelopmental impairment was common and occurred even in genetically negative patients, supporting broad genetic evaluation together with systematic developmental surveillance for all affected children, independent of syndromic classification.
LEVEL OF EVIDENCE: Level III-Retrospective comparative study.