Jon Foss-Skiftesvik, Carl Christian Larsen, Ulrik Kristoffer Stoltze, Thomas Kofod, Hanne Hove, Lars Bøgeskov, Elsebet Østergaard
{"title":"The role of pathogenic TCF12 variants in children with coronal craniosynostosis-a systematic review with addition of two novel cases.","authors":"Jon Foss-Skiftesvik, Carl Christian Larsen, Ulrik Kristoffer Stoltze, Thomas Kofod, Hanne Hove, Lars Bøgeskov, Elsebet Østergaard","doi":"10.1007/s00381-024-06544-z","DOIUrl":null,"url":null,"abstract":"<p><p>Craniosynostosis constitutes one of the most common congenital cranial malformations, affecting approximately 6/10,0000 live births. A genetic etiology has long been known for several forms of syndromic craniosynostosis, including pathogenic variants in TWIST1 and FGFR3 in children with Saethre-Chotzen and Muenke syndrome. Over the last decade, reports of genetic aberrations in TCF12 in children with craniosynostosis have emerged, in particular in cases with premature closure of the coronal suture(s). In this study, we, therefore, systematically reviewed the rapidly growing knowledge of TCF12-related coronal craniosynostosis, clearly illustrating its high degree of genotype and phenotype variability. With the two novel cases presented, at least 113 cases of TCF12-related coronal craniosynostosis have currently been reported. By pooling data from several prospectively collected undifferentiated craniosynostosis cohorts (n<sub>total</sub> = 770), we estimate a prevalence of pathogenic TCF12 variants of at least 2%. Overall, pathogenic germline variants in TCF12 are relatively frequent in children with coronal craniosynostosis, accounting for ∼10-20% of TWIST1- and FGFR1/2/3-negative cases, with even higher rates for bicoronal and syndromic cases. Genetic counseling is recommended for all children with craniosynostosis, and involvement of the coronal suture(s) should precipitate TCF12 testing.</p>","PeriodicalId":9970,"journal":{"name":"Child's Nervous System","volume":null,"pages":null},"PeriodicalIF":1.3000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Child's Nervous System","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00381-024-06544-z","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/27 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Craniosynostosis constitutes one of the most common congenital cranial malformations, affecting approximately 6/10,0000 live births. A genetic etiology has long been known for several forms of syndromic craniosynostosis, including pathogenic variants in TWIST1 and FGFR3 in children with Saethre-Chotzen and Muenke syndrome. Over the last decade, reports of genetic aberrations in TCF12 in children with craniosynostosis have emerged, in particular in cases with premature closure of the coronal suture(s). In this study, we, therefore, systematically reviewed the rapidly growing knowledge of TCF12-related coronal craniosynostosis, clearly illustrating its high degree of genotype and phenotype variability. With the two novel cases presented, at least 113 cases of TCF12-related coronal craniosynostosis have currently been reported. By pooling data from several prospectively collected undifferentiated craniosynostosis cohorts (ntotal = 770), we estimate a prevalence of pathogenic TCF12 variants of at least 2%. Overall, pathogenic germline variants in TCF12 are relatively frequent in children with coronal craniosynostosis, accounting for ∼10-20% of TWIST1- and FGFR1/2/3-negative cases, with even higher rates for bicoronal and syndromic cases. Genetic counseling is recommended for all children with craniosynostosis, and involvement of the coronal suture(s) should precipitate TCF12 testing.
期刊介绍:
The journal has been expanded to encompass all aspects of pediatric neurosciences concerning the developmental and acquired abnormalities of the nervous system and its coverings, functional disorders, epilepsy, spasticity, basic and clinical neuro-oncology, rehabilitation and trauma. Global pediatric neurosurgery is an additional field of interest that will be considered for publication in the journal.