Bilateral coronal craniosynostosis with novel TWIST1 mutation

Syndromic craniosynostosis is characterized by premature fusion of one or more cranial sutures, often in association with multisystem anomalies affecting the airway, cardiovascular, musculoskeletal, and neurodevelopmental systems. Variants in genes such as TWIST1 contribute to phenotypic heterogeneity and may influence surgical timing, risk stratification, and long-term craniofacial planning. We present a severe syndromic craniosynostosis phenotype associated with a previously undescribed TWIST1 variant and discuss perioperative considerations of staged cranial vault reconstruction.

We report a female infant with craniofacial dysmorphism and multisuture craniosynostosis with complete fusion of the bilateral coronal sutures and widening of the sagittal and metopic sutures. Her phenotype included hypertelorism, frontal bossing, exophthalmos, micrognathia, microtia with aural atresia, cleft palate, and limb anomalies. Additional comorbidities included cardiovascular, respiratory, and feeding abnormalities. Genetic testing revealed a novel TWIST1 missense variant (c.423C > G; p.Asp141Glu), not previously reported in population databases or associated with TWIST1-related disease. Due to progressive dysmorphology and worsening orbital proptosis, early strip craniectomy was performed to permit brain-driven anterior vault expansion. At 8.8 months, PVDO with virtual surgical planning was performed to improve intracranial volume and cranial morphology. The postoperative course was complicated by respiratory failure, cardiac arrest, intracranial abscess, and pseudomeningocele requiring surgical management.

This case highlights the expanding genotypic and phenotypic variability associated with TWIST1 alterations. It emphasizes the need for ongoing genetic investigation to delineate pathogenic variants, improve prognostication, and refine surgical planning in complex craniosynostosis.