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

Neuropediatrics. 2015 Apr;46(2):98-103. doi: 10.1055/s-0034-1399755. Epub 2015 Feb 2.

Abstract

Pediatric movement disorders are still a diagnostic challenge, as many patients remain without a (genetic) diagnosis. Magnetic resonance imaging (MRI) pattern recognition can lead to the diagnosis. MEGDEL syndrome (3-MethylGlutaconic aciduria, Deafness, Encephalopathy, Leigh-like syndrome MIM #614739) is a clinically and biochemically highly distinctive dystonia deafness syndrome accompanied by 3-methylglutaconic aciduria, severe developmental delay, and progressive spasticity. Mutations are found in SERAC1, encoding a phosphatidylglycerol remodeling enzyme essential for both mitochondrial function and intracellular cholesterol trafficking. Based on the homogenous phenotype, we hypothesized an accordingly characteristic MRI pattern. A total of 43 complete MRI studies of 30 patients were systematically reevaluated. All patients presented a distinctive brain MRI pattern with five characteristic disease stages affecting the basal ganglia, especially the putamen. In stage 1, T2 signal changes of the pallidum are present. In stage 2, swelling of the putamen and caudate nucleus is seen. The dorsal putamen contains an "eye" that shows no signal alteration and (thus) seems to be spared during this stage of the disease. It later increases, reflecting progressive putaminal involvement. This "eye" was found in all patients with MEGDEL syndrome during a specific age range, and has not been reported in other disorders, making it pathognomonic for MEDGEL and allowing diagnosis based on MRI findings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basal Ganglia / pathology*
  • Child, Preschool
  • Deafness / complications
  • Deafness / genetics
  • Deafness / pathology*
  • Disease Progression
  • Dystonic Disorders / complications
  • Dystonic Disorders / genetics
  • Dystonic Disorders / pathology*
  • Humans
  • Infant
  • Magnetic Resonance Imaging
  • Mitochondrial Diseases / complications
  • Mitochondrial Diseases / pathology*
  • Putamen / pathology
  • Syndrome