Background: Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous neurodegenerative disorders characterized 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: Characterization the human consequences of the “rumpshaker mutation”.
Patients: A second 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 MRI of the brains 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 No definite symptoms in the female carriers could be ascribed to the mutation. Our data suggest the pathology to be an underlying dysmyelinating disorder in combination with a central axonal degeneration.