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SMAD6 variants in nonsyndromic craniosynostosis

European Journal of Human Genetics volume 31, pages 611–612 (2023)Cite this article

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Premature fusion of the cranial sutures (craniosynostosis) is one of the most frequent congenital craniofacial anomalies, occurring once in every 2000 births. Syndromic craniosynostoses account for ~15% of cases and demonstrate Mendelian patterns of inheritance with well-established genetic causes [1]; however, nonsyndromic CS, accounting for ~85% of cases, is genetically heterogeneous and largely unexplored. In this article by di Rocco et al., the authors describe a molecular etiology in 12.9% of nonsyndromic sagittal and metopic CS cases in a cohort of 101 patients [2]. Most notable among genetic causes, heterozygous mutations in SMAD6 were identified in 7% of cases, with neurodevelopmental testing demonstrating delayed language acquisition in affected probands. The incidence of SMAD6 mutations in nonsyndromic CS and the presence of associated adverse neurodevelopmental consequences are consistent with prior studies of SMAD6-associated CS [3,4,5,6,7].

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  1. Hansjörg Wyss Department of Plastic Surgery, NYU Langone Medical Center, New York, NY, USA

    Andrew T. Timberlake

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Timberlake, A.T. SMAD6 variants in nonsyndromic craniosynostosis. Eur J Hum Genet 31, 611–612 (2023). https://doi.org/10.1038/s41431-023-01317-9

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