Mandibulofacial dysostosis with microcephaly: A case presenting with seizures

Area of Science:

• Genetics
• Neurology
• Developmental Biology

Background:

• Mandibulofacial dysostosis with microcephaly is a rare congenital disorder characterized by craniofacial abnormalities and intellectual disability.
• Seizures are not typically considered a primary feature of this condition, making their presentation noteworthy.

Observation:

• A 6-year-old Korean boy with microcephaly, malar and mandibular hypoplasia, and deafness presented with recurrent seizures starting at 21 months of age.
• Electroencephalography showed right frontal lobe spike discharges, and MRI revealed lateral ventricle dilatation and reduced frontal lobe volume.
• Whole exome sequencing identified a de novo frameshift mutation (c.2698_2701 del) in the EFTUD2 gene.

Findings:

• The identified EFTUD2 mutation is associated with the observed craniofacial anomalies and microcephaly.
• The epileptic focus correlated with the reduced frontal lobe volume, suggesting a direct link between the genetic defect and neurological manifestations.
• This case highlights seizures as a significant clinical feature in mandibulofacial dysostosis with microcephaly.

Implications:

• The findings suggest that EFTUD2 mutations can lead to embryonic developmental defects affecting both craniofacial structures and brain development, resulting in epilepsy.
• Early identification and management of seizures are crucial for patients with this condition.
• Further research into the role of EFTUD2 in neurodevelopment may uncover new therapeutic targets.