Magnetic Resonance Imaging of a Unique Mutation in a Family with Pelizaeus-Merzbacher Disease

Division of Neuroradiology, Department of Diagnostic Imaging, The Hospital for Sick Children, Ontario, Canada.
American Journal of Medical Genetics Part A (Impact Factor: 2.16). 03/2010; 152A(3):748-52. DOI: 10.1002/ajmg.a.33305
Source: PubMed


Pelizaeus-Merzbacher disease (PMD) is a rare dysmyelination disorder, characterized by significant developmental delay, truncal hypotonia, spasticity, dysarthria, and nystagmus. Conventional magnetic resonance (MR) images demonstrate discordance of myelin maturation, while newer MR techniques, such as MR spectroscopy and diffusion tensor imaging, may be helpful in disease assessment. We report on a family of two young boys and their mother who share the same unusual 4-bp deletion of the PLP1 gene: c51_54 del TTCC, causing truncation of the PLP1 in exon 2. The brain MRI appearances in this unique deletion, using newer MR imaging, are described.

18 Reads
  • Source
    • "The clinical features of PMD are variable and include nystagmus, psychomotor delay, seizure, stridor, feeding difficulties, ataxia, and hypotonia progressing to spasticity. Moreover, the degree of dysmyelination is correlated with the severity of the clinical manifestations4,9,11). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Pelizaeus-Merzbacher disease (PMD) is a rare, X-linked recessive disorder characterized by dysmyelination in the central nervous system. PMD results from deletion, mutation, or duplication of the proteolipid protein gene (PLP1) located at Xq22, leading to the failure of axon myelination by oligodendrocytes in the central nervous system. PMD may be suspected when there are clinical manifestations such as nystagmus, developmental delays, and spasticity, and genetic analysis can confirm the diagnosis. Further diagnostic manifestations of the disease include a lack of myelination on brain magnetic resonance (MR) imaging and aberrant N-acetyl aspartate (NAA) and choline concentrations that reflect axonal and myelination abnormalities on phroton MR spectroscopy. We report 5 cases of PMD (in 1 girl and 4 boys). PLP1 duplication was detected in 2 patients. Brain MR analyses and MR spectroscopy were performed for all the patients. The brain MR images showed white matter abnormalities typical of PMD, and the MR spectroscopic images showed diverse patterns of NAA, creatinine, and choline concentrations. We propose that MR spectroscopic analysis of metabolic alterations can aid the PMD diagnosis and can contribute to a better understanding of the pathogenesis of the disease.
    Full-text · Article · Oct 2012 · Korean Journal of Pediatrics
  • Source
    • "Both the Po and Dr measures showed the largest relative group differences (Table 2). The increased radial diffusivity, Dr, measurements in the sh pups are consistent with studies in dysmyelination models like the shiverer mouse and the jimpy mouse (Song et al., 2002; Tyszka et al., 2006; Harsan et al., 2006, 2007), the myelin deficient (md) rat brain and spinal cord (Biton et al., 2007; Bar-Shir et al., 2009), and with abnormal diffusion anisotropy reported in humans with PMD (Ono et al., 1994 & 1997; Sener 2004; Miller et al., 2010). It is believed that Dr is a fairly specific biomarker of myelin (Song et al., 2002) although its validity in regions of complex crossing WM has been questioned (Wheeler-Kingshot and Cercignani, 2009). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent studies in rodents have demonstrated that diffusion imaging is highly sensitive to differences in myelination. These studies suggest that demyelination/dysmyelination cause increases in the radial diffusivity from diffusion tensor imaging (DTI) measurements and decreases in the restricted diffusion component from high b-value diffusion-weighted imaging experiments. In this study, the shaking pup (sh pup), a canine model of dysmyelination, was studied on a clinical MRI scanner using a combination of conventional diffusion tensor imaging and high b-value diffusion-weighted imaging methods. Diffusion measurements were compared between control dogs and sh pups in the age range 3 months to 16 months, which is similar to the period of early childhood through adolescence in humans. The study revealed significant group differences in nearly all diffusion measures with the largest differences in the zero-displacement probability (Po) from high b-value DWI and the radial diffusivity from DTI, which are consistent with the observations from the published rodent studies. Age-related changes in Po, FA, mean diffusivity, radial diffusivity and axial diffusivity were observed in whole brain white matter for the control dogs, but not the sh pups. Regionally, age-related changes in the sh pup white matter were observed for Po, mean diffusivity and radial diffusivity in the internal capsule, which may be indicative of mild myelination. These studies demonstrate that DWI may be used to study myelin abnormalities and brain development in large animal models on clinical MRI scanners, which are more amenable to translation to human studies.
    Full-text · Article · Jul 2011 · NeuroImage
  • [Show abstract] [Hide abstract]
    ABSTRACT: Anisotropic water diffusion in neural fibers such as nerve, white matter in spinal cord, or white matter in brain forms the basis for the utilization of diffusion tensor imaging (and other models) to track fiber pathways. The fact that water diffusion is sensitive to the underlying tissue microstructure provides a unique method of assessing the orientation and integrity of these neural fibers, which may be useful in assessing a number of neurological disorders. The purpose of this chapter is to characterize the relationship of NMR measurements of water diffusion and its anisotropy (i.e. directional dependence) with the components of the underlying microstructure of neural fibers. The emphasis will be on model neurological systems both in vitro and in vivo.
    No preview · Chapter · Dec 2009
Show more