European Journal of Pediatrics

, Volume 174, Issue 1, pp 113–118 | Cite as

MED20 mutation associated with infantile basal ganglia degeneration and brain atrophy

  • Julia Vodopiutz
  • Maria T. Schmook
  • Vassiliki Konstantopoulou
  • Barbara Plecko
  • Susanne Greber-Platzer
  • Marc Creus
  • Rainer Seidl
  • Andreas R. Janecke
Original Article


Infantile movement disorders are rare and genetically heterogeneous. We set out to identify the disease-causing mutation in siblings with a novel recessive neurodegenerative movement disorder. Genetic linkage analysis and whole-exome sequencing were performed in the original family. A cohort of six unrelated patients were sequenced for further mutations in the identified candidate gene. Pathogenicity of the mutation was evaluated by in silico analyses and by structural modeling. We identified the first and homozygous mutation (p.Gly114Ala) in the Mediator subunit 20 gene (MED20) in siblings presenting with infantile-onset spasticity and childhood-onset dystonia, progressive basal ganglia degeneration, and brain atrophy. Mediator refers to an evolutionarily conserved multi-subunit RNA polymerase II co-regulatory complex. Pathogenicity of the identified missense mutation is suggested by in silico analyses, by structural modeling, and by previous reporting of mutations in four distinct Mediator subunits causing neurodegenerative phenotypes. No further MED20 mutations were detected in this study.

Conclusion: We delineate a novel infantile-onset neurodegenerative movement disorder and emphasize the Mediator complex as critical for normal neuronal function. Definitive proof of pathogenicity of the identified MED20 mutation will require confirmation in unrelated patients.


Dystonia Infantile neurodegeneration Exome sequencing Basal ganglia degeneration Mediator complex 



Head circumference




Mediator complex


Mediator subunit 20 gene


Magnetic resonance imaging


Neurodegeneration with brain iron accumulation


National Center for Biotechnology Information


Nucleoporin 62 kDa gene


Polymerase chain reaction


Protein Data Bank

PolyPhen 2

Polymorphism Phenotyping version 2


Standard deviations


Sorting Intolerant from Tolerant


Single nucleotide polymorphism



The authors thank Sabine Möstl (Medical University of Vienna) for video documentation and Dr. Malvina Herceg (Medical University of Vienna) for performing NCV. The study was partially funded by the Austrian Society of Pediatrics (ÖGKJ) and an in-house grant of the Department of Pediatrics and Adolescent Medicine of Medical University Vienna (both to J.V.).

The Austrian Society of Pediatrics had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication.

Conflict of interest

The authors declare no competing financial interests.

Supplementary material

Video 1 Patient 1 at 16 years of age. Cheerful disposition, no voluntary movements when lying in the prone position. Marked truncal hypotonia upon passive rotation from prone to supine position. Increased muscle tone is evident during rapid passive motion of the upper but less so of lower extremities. Deep tendon reflexes cannot be elicited and pyramidal tracts signs are absent. (WMV 4,294 kb)
Video 2 Patient 1, part 2. The patient is asked to grab a toy which induces generalized dystonia with constant mouth opening and fixed posture of left upper and lower extremities. Inability to grasp objects with her right hand with dystonic posture of fingers. Inability to walk and bradykinesia. (WMV 5,372 kb)
Video 3 Patient 2 at 2 years of age. Mild muscle weakness revealed during active rotation from prone to supine position and when getting into the upright position. Movements are slow and uncoordinated for her age and the right hand is fisted while crawling. There is no dystonia present. (WMV 2,950 kb)
Video 4 Patient 2, part 2. She presents with increased muscle tone of lower and upper limbs and brisk reflexes, Babinski sign is absent. She has no speech development. (WMV 3,169 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Julia Vodopiutz
    • 1
  • Maria T. Schmook
    • 2
  • Vassiliki Konstantopoulou
    • 1
  • Barbara Plecko
    • 3
  • Susanne Greber-Platzer
    • 1
  • Marc Creus
    • 4
  • Rainer Seidl
    • 1
  • Andreas R. Janecke
    • 5
    • 6
  1. 1.Department of Pediatrics and Adolescent MedicineMedical University of ViennaWienAustria
  2. 2.Department of Biomedical Imaging and Image-guided Therapy, Division of Neuroradiology and Musculoskeletal RadiologyMedical University of ViennaWienAustria
  3. 3.Division of NeuropediatricsUniversity Children’s Hospital ZürichZurichSwitzerland
  4. 4.Department of ChemistryUniversity of BaselBaselSwitzerland
  5. 5.Department of Pediatrics IInnsbruck Medical UniversityInnsbruckAustria
  6. 6.Division of Human GeneticsInnsbruck Medical UniversityInnsbruckAustria

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