Bilateral coronal craniosynostosis with novel TWIST1 mutation

Area of Science:

• Genetics
• Pediatric Surgery
• Craniofacial Surgery

Background:

• Syndromic craniosynostosis involves premature suture fusion and multisystem anomalies.
• TWIST1 gene variants contribute to diverse phenotypes and impact surgical strategies.
• Understanding genetic heterogeneity is crucial for managing craniosynostosis.

Purpose of the Study:

• To report a severe syndromic craniosynostosis case with a novel TWIST1 variant.
• To discuss perioperative management of staged cranial vault reconstruction.
• To highlight the genotypic and phenotypic variability in TWIST1-related craniosynostosis.

Main Methods:

• Case report of a female infant with craniofacial dysmorphism and multisuture craniosynostosis.
• Genetic testing identified a novel TWIST1 missense variant (c.423C>G; p.Asp141Glu).
• Staged surgical interventions included strip craniectomy and posterior vault distraction osteogenesis (PVDO) with virtual planning.

Main Results:

• The infant presented with hypertelorism, micrognathia, cleft palate, limb anomalies, and cardiovascular/respiratory issues.
• Postoperative complications included respiratory failure, cardiac arrest, intracranial abscess, and pseudomeningocele.
• The novel TWIST1 variant expanded the known spectrum of disease-associated alterations.

Conclusions:

• This case demonstrates significant genotypic and phenotypic variability in TWIST1 alterations.
• Emphasizes the need for genetic investigation to identify pathogenic variants.
• Highlights the importance of genetic findings for prognostication and surgical planning in complex craniosynostosis.