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Hereditary spastic paraplegia caused by the PLP1 ‘rumpshaker mutation’
  1. Kirsten Svenstrup1,2,
  2. Geneviève Giraud3,
  3. Odile Boespflug-Tanguy3,4,
  4. Else R Danielsen5,
  5. Carsten Thomsen5,
  6. Kirsten Rasmussen6,
  7. Ian Law7,
  8. Asmus Vogel2,
  9. Jette Stokholm2,
  10. Clarissa Crone8,
  11. Lena E Hjermind1,2,
  12. Jørgen E Nielsen1,2
  1. 1Section of Neurogenetics, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark
  2. 2Memory Disorders Research Group, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark
  3. 3INSERM UMR 931-CNRS 6247, GReD, Clermont University, Faculty of Médecine Clermont-Ferrand, Clermont-Ferrand, France
  4. 4CHU de Clermont-Ferrand, Department of Human Genetics, Reference Center for Leukodystrophies, Clermont-Ferrand, France
  5. 5Department of Radiology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark
  6. 6Department of Clinical Genetics, University Hospital of Odense, Odense, Denmark
  7. 7Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark
  8. 8Department of Clinical Neurophysiology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark
  1. Correspondence to Dr Kirsten Svenstrup, Section of Neurogenetics, The Panum Institute, Building 24.4, Blegdamsvej 3b, DK-2200 Copenhagen N, Denmark; ksvenstrup{at}


Background Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous neurodegenerative disorders characterised by progressive spasticity and weakness in the lower limbs. Mutations in PLP1 on the X chromosome cause spastic paraplegia type 2 (SPG2) or the allelic Pelizaeus–Merzbacher Disease (PMD). The PLP1 protein is a major myelin protein involved in stabilisation and maintenance of the myelin sheath. The function of the protein has been studied in the rumpshaker mouse, which is a model of SPG2/PMD.

Objective To characterise the phenotype of patients with the ‘rumpshaker mutation.’

Patients A family with HSP caused by the ‘rumpshaker mutation.’

Results The patients showed nystagmus during infancy and had early onset of HSP. They had normal cognition, and cerebral MRI showed relatively unspecific white matter abnormalities on T2 sequences without clear progression. Urinary urgency was reported among the female carriers. MRS of both patients showed increased myo-inositol in the white matter, while decreased N-acetylaspartate was found exclusively in the oldest patient. All evoked potential examinations were compatible with severe central demyelination, while no signs of peripheral demyelination or axonal degeneration were found. 18F-FDG-PET scans were normal.

Conclusion The phenotypes of the patients reported here are the mildest described to be caused by the rumpshaker mutation and represent the mildest form among the spectrum of PLP1 related disorders. No definite symptoms in the female carriers could be ascribed to the mutation. These data suggest the pathology to be an underlying dysmyelinating disorder in combination with a central axonal degeneration.

  • Hereditary spastic paraplegia
  • HSP
  • SPG2
  • PLP1
  • rumpshaker

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  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Ethics approval was provided by the Copenhagen Ethics commitee.

  • Provenance and peer review Not commissioned; externally peer reviewed.