Heterozygous mutations in ERF cause syndromic craniosynostosis with multiple suture involvement

Area of Science:

• Genetics
• Pediatric Surgery
• Developmental Biology

Background:

• Craniosynostosis is a complex condition with diverse genetic causes.
• Identifying specific genetic diagnoses is crucial for effective patient management.
• Known genetic factors include mutations in FGFR1, FGFR2, FGFR3, TWIST1, and EFNB1.

Purpose of the Study:

• To investigate the role of ERF gene mutations in genetically undiagnosed craniosynostosis cases.
• To determine the frequency of ERF mutations in patients with sagittal or multi-suture synostosis.

Main Methods:

• Sequencing of the coding regions of the ERF gene.
• Analysis of 40 patients with multi-suture or sagittal suture craniosynostosis.

Main Results:

• Heterozygous ERF mutations were identified in two individuals (5% of the cohort).
• Affected individuals presented with pansynostosis or bilateral coronal and metopic synostosis.
• Clinical features included Chiari I malformation and characteristic dysmorphic features.

Conclusions:

• ERF mutations represent a novel genetic cause of craniosynostosis.
• ERF-related craniosynostosis should be considered in patients with sagittal or multi-suture synostosis.
• Molecular diagnosis of ERF mutations is clinically important for management.