Mandibular dysostosis without microphthalmia caused by OTX2 deletion

Area of Science:

• Genetics
• Developmental Biology
• Craniofacial Development

Background:

• The OTX2 homeobox gene is essential for craniofacial development in early embryogenesis.
• OTX2 mutations are primarily associated with anophthalmia/microphthalmia, ranging in severity.
• Understanding the full spectrum of OTX2-related disorders is crucial for genetic diagnosis.

Observation:

• A patient presented with mandibular dysostosis, a rare condition affecting jaw development.
• Array comparative genomic hybridization (CGH) identified a 120 kb deletion encompassing the entire OTX2 coding sequence.
• Comprehensive ophthalmologic examinations revealed no ocular malformations in the patient.

Findings:

• This case represents the first documented instance of mandibular dysostosis caused by a complete OTX2 coding sequence deletion.
• The identified deletion leads to OTX2 haploinsufficiency, impacting craniofacial development.
• The absence of ocular defects in this patient expands the known clinical manifestations of OTX2 gene alterations.

Implications:

• The findings suggest that OTX2 haploinsufficiency should be considered in the differential diagnosis of isolated mandibular dysostosis.
• This research refines the clinical spectrum associated with OTX2 mutations, highlighting its role beyond ocular development.
• Genetic testing for OTX2 deletions can aid in diagnosing rare craniofacial anomalies.