New Pattern of Sutural Synostosis Associated With TWIST Gene Mutation and Saethre-Chotzen Syndrome

Abstract

The authors present a new and unique pattern of sutural fusion "peace sign synostosis" (PSS) characterized by synostosis of the metopic, bicoronal, and sagittal sutures and associated with abnormalities of the TWIST1 gene known to be associated with Saethre-Chotzen syndrome (SCS). To do so, we performed a retrospective review of patients with bicoronal, metopic, and at least partial anterior sagittal synostoses at the Children's Hospital of Philadelphia and Seattle Children's Hospital. Patients' demographics, genetic analysis, perioperative and clinic notes were reviewed. Five patients were identified with PSS and abnormalities of TWIST1 consistent with SCS. One patient, with the longest follow-up of 7 years, underwent 5 intracranial procedures and required a ventriculoperitoneal (VP) shunt. The remaining 4 patients underwent posterior cranial vault distraction as the initial procedure, followed by anterior cranial vault remodeling. Two patients required a VP shunt. To conclude, synostosis of the metopic, bicoronal, and sagittal sutures (PSS) appears to be associated with SCS and produces a characteristic skull morphology that can be readily identified on physical examination. Early data suggest a high rate of reoperation, increased necessity for a VP shunt, and potential complications. Of note, this novel phenotype had not been previously observed at our respective institutions, reported in the literature, or observed in association with TWIST1 abnormalities as described in association with SCS.

Genetic advances in craniosynostosis

“…There have also been reported patients with cxNCS involving sagittal, metopic and coronal sutures who were found to have TWIST1 mutations. Mutations in TWIST1 also cause Saethre-Chotzen syndrome [Sauerhammer et al, 2014a; Tahiri et al, 2015]. Therefore, genetic testing of SMAD6, FGFR1, 2, 3 and TWIST1 is indicated for individuals with cxNCS, and TCF12 and ZIC1 sequencing should be considered when mutations in other genes have been excluded.…”

Novel Molecular Markers for Breast Cancer

“…137 Twist1 is evolutionarily conserved from invertebrates to humans, 135 and mutations in the Twist1 gene have been known to cause Saethre-Chotzen syndrome (SCS) in humans. 138–140 SCS is a rare autosomal-dominant hereditary disorder showing craniosynostosis, facial asymmetry, ptosis of eyelids, widely spaced eyes, and broad nasal bridge, proving its essential role in normal human development. The closely related Twist2 gene ( Dermo1 ) has been mapped onto human chromosome 2q37.3 and has been considered to inhibit osteoblast maturation and maintain cells in a preosteoblast phenotype; 141 however, not much is known about its role in carcinogenesis.…”

Craniosynostosis Syndromes: Genetics to Imaging

“…However, patients characteristically demonstrate bifid hallux rather than frank syndactyly. [34][35][36][37][38] Waardenburg syndrome, or ACS IV, is associated with various mutations that affect melanin production and subsequent development of the face, hair, skin, eyes, and inner ears. Clinical features include white forelock of hair (poliosis), iris heterochromia or hypochromia, synophrys, dystopia canthorum, cleft lip/palate, skin hypopigmentation, and sensorineural hearing loss (often unilateral or asymmetric).…”