Eyes on MEGDEL: distinctive basal ganglia involvement in dystonia deafness syndrome

Area of Science:

• Neuroimaging
• Genetics
• Pediatric Neurology

Background:

• Pediatric movement disorders often pose diagnostic challenges, with many patients lacking a genetic diagnosis.
• MEGDEL syndrome (3-MethylGlutaconic aciduria, Deafness, Encephalopathy, Leigh-like syndrome) is a distinct dystonia-deafness syndrome with severe developmental delay and spasticity.
• Mutations in the SERAC1 gene, crucial for mitochondrial function and cholesterol trafficking, underlie MEGDEL syndrome.

Purpose of the Study:

• To identify a characteristic brain MRI pattern in patients with MEGDEL syndrome.
• To determine if MRI findings can aid in the diagnosis of MEGDEL syndrome.

Main Methods:

• Systematic reevaluation of 43 complete MRI studies from 30 patients with MEGDEL syndrome.
• Analysis of MRI findings across different disease stages, focusing on the basal ganglia, particularly the putamen.

Main Results:

• A distinctive brain MRI pattern was observed in all patients, characterized by five disease stages affecting the basal ganglia.
• Early stages show T2 signal changes in the pallidum and putaminal/caudate swelling.
• A pathognomonic "eye" sign, representing a spared dorsal putamen, was identified in a specific age range, absent in other disorders.

Conclusions:

• The characteristic MRI pattern, including the unique "eye" sign, is pathognomonic for MEGDEL syndrome.
• MRI pattern recognition can facilitate diagnosis in patients with MEGDEL syndrome, even without a prior genetic diagnosis.
• This finding highlights the utility of neuroimaging in diagnosing rare pediatric movement disorders.