Mandibular Distraction Osteogenesis in Monozygotic Twins With Structural-Dominant ALG8 Variants

Area of Science:

• Genetics
• Developmental Biology
• Metabolic Disorders

Background:

• Biallelic ALG8 mutations usually cause lethal congenital disorders of glycosylation (CDG-Ih).
• Congenital disorders of glycosylation are a group of rare genetic diseases affecting multiple body systems.

Purpose of the Study:

• To report a unique case of monozygotic twins with ALG8 mutations presenting with Pierre Robin sequence and orofacial-digital-like features.
• To highlight the successful management of severe airway obstruction using mandibular distraction osteogenesis in this complex genetic background.

Main Methods:

• Whole-exome sequencing to identify compound heterozygous variants in the ALG8 gene.
• Clinical assessment and surgical intervention (mandibular distraction osteogenesis) for airway management.

Main Results:

• Identified compound heterozygous ALG8 variants (c.140C>T and c.1349+1G>A) in monozygotic twins.
• Successful management of severe airway obstruction and respiratory weaning via bilateral mandibular distraction osteogenesis.
• Achieved complete respiratory weaning and enabled oral feeding post-intervention.

Conclusions:

• Specific ALG8 defects can present as a structural-dominant "metabolic ciliopathy," expanding the known phenotypic spectrum of CDG.
• Mandibular distraction osteogenesis is a safe and effective life-saving intervention for complex genetic-metabolic conditions, even with theoretical risks.