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Introduction <p>Mutations in TCF12 are identified in 10–20% of coronal craniosynostoses negative for TWIST1 and FGFR mutations, with autosomal dominant inheritance, incomplete penetrance, and wide phenotypic variability. The recognized phenotypic spectrum includes coronal synostosis, craniofacial dysmorphism, ptosis, strabismus, mild syndactyly, and neurocognitive alterations. However, axial skeletal segmentation anomalies have not been previously reported in association with TCF12 mutations.</p> Case presentation <p>We present the case of a 9-year-old male with right unicoronal craniosynostosis treated by endoscopic suturectomy at 3&#xa0;months of age. Genetic testing identified a pathogenic heterozygous variant in TCF12 (c.1691C&gt;G; p.Ser564*). During follow-up, spine evaluation revealed a left lumbar congenital muscular scoliosis (43° Cobb, L1–L5), an L5 hemivertebra, and a posterior sacral fusion deficit, confirmed on radiography and MRI. Cranial MRI showed mild supratentorial ventriculomegaly. Neurocognitive developmental delay with social communication difficulties was also noted. The same TCF12 mutation was identified in the phenotypically asymptomatic father. Over 6 years of follow-up, the lumbar curve remained stable and was managed conservatively.</p> Conclusion <p>This case represents the first reported association between coronal craniosynostosis due to a TCF12 mutation and axial skeletal segmentation anomalies. Given the broad embryonic expression of TCF12 and its role in osteoblast differentiation, this finding suggests a wider effect on axial skeletal morphogenesis beyond the cranial vault. We propose that systematic spinal evaluation should be considered in patients with TCF12-related craniosynostosis presenting with signs of trunk asymmetry, and that a multidisciplinary follow-up, including neurosurgery, orthopedics, ophthalmology, and neurodevelopmental assessment, is essential to detect and manage the full phenotypic spectrum.</p>

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Lumbar hemivertebra associated with coronal craniosynostosis due to TCF12 mutation: an expansion of the axial skeletal phenotype

  • 期刊论文

  • 发表日期：

    2026年5月11日

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  • Miguel Caparrós Calle,
  • Juan Sánchez Palacios,
  • Jesús Gallego Álvarez,
  • Ariel Goltzman Peist

摘要

Introduction

Mutations in TCF12 are identified in 10–20% of coronal craniosynostoses negative for TWIST1 and FGFR mutations, with autosomal dominant inheritance, incomplete penetrance, and wide phenotypic variability. The recognized phenotypic spectrum includes coronal synostosis, craniofacial dysmorphism, ptosis, strabismus, mild syndactyly, and neurocognitive alterations. However, axial skeletal segmentation anomalies have not been previously reported in association with TCF12 mutations.

Case presentation

We present the case of a 9-year-old male with right unicoronal craniosynostosis treated by endoscopic suturectomy at 3 months of age. Genetic testing identified a pathogenic heterozygous variant in TCF12 (c.1691C>G; p.Ser564*). During follow-up, spine evaluation revealed a left lumbar congenital muscular scoliosis (43° Cobb, L1–L5), an L5 hemivertebra, and a posterior sacral fusion deficit, confirmed on radiography and MRI. Cranial MRI showed mild supratentorial ventriculomegaly. Neurocognitive developmental delay with social communication difficulties was also noted. The same TCF12 mutation was identified in the phenotypically asymptomatic father. Over 6 years of follow-up, the lumbar curve remained stable and was managed conservatively.

Conclusion

This case represents the first reported association between coronal craniosynostosis due to a TCF12 mutation and axial skeletal segmentation anomalies. Given the broad embryonic expression of TCF12 and its role in osteoblast differentiation, this finding suggests a wider effect on axial skeletal morphogenesis beyond the cranial vault. We propose that systematic spinal evaluation should be considered in patients with TCF12-related craniosynostosis presenting with signs of trunk asymmetry, and that a multidisciplinary follow-up, including neurosurgery, orthopedics, ophthalmology, and neurodevelopmental assessment, is essential to detect and manage the full phenotypic spectrum.