Clinical spectrum and outcomes in families with coronal synostosis and TCF12 mutations

Abstract

TCF12 mutations have been reported very recently in coronal synostosis. We report several cases of familial coronal synostosis among four families harbouring novel TCF12 mutations. We observed a broad interfamilial phenotypic spectrum with features overlapping with the Saethre-Chotzen syndrome. TCF12 molecular testing should be considered in patients with unilateral- or bilateral-coronal synostosis associated or not with syndactyly, after having excluded mutations in the TWIST1 gene and the p.Pro250Arg mutation in FGFR3.

Figure 1

Pedigrees of the families with mutations in TCF12. Clear symbols denote unaffected individuals, and black symbols denote clinically-affected individuals either with or without craniosynostosis. In family #3, patients II-1, III-1, and IV-1 only showed syndactyly of the feet. *: available DNA. Dot: abnormal extremities without craniosynostosis.

Figure 2

Clinical phenotypes. Family #1. Patient II-5 (a–c) at age 6 months. She presented with left plagiocephaly secondary to the early fusion of the left coronal suture: the two frontal photographs show unilateral coronal synostosis (a); computed tomography (CT) showing the left frontal deformation (b); posterior and anterior facial X-ray (c) with the characteristic harlequin's eye at the time of diagnosis (c-left) and at the time of surgery (c-right); note also the deviation of the sagittal suture. Family #1. Patient III-3 (d–g), son of II-5, at age 5 months. Frontal and lateral pictures showing bicoronal synostosis (d); 3D-CT showing the bilateral fusion of the coronal sutures (e); 2D CT image showing the fusion of the coronal sutures (f), intra-operative picture showing the deformation at surgery and the planned osteotomy lines in blue (g). Family #2, patient II-2. Small-sized ear with prominent crus (h). Family #4, patient II-2. brachydactyly (i). A full colour version of this figure is available at The European Journal of Human Genetics online.

Figure 3

Mutations of the TCF12 gene. (a) Family #1: heterozygous duplication, c.1366dupA, (b) Family #2: heterozygous deletion, c.1071delG, (c) Family #3: heterozygous mutation, c.1838G>A, and (d) Family #4, heterozygous deletion, c.1000_1001delCA.