Unusual clinical and magnetic resonance imaging findings in a family with proteolipid protein gene mutation

Background: Pelizaeus-Merzbacher disease (PMD) and a complicated form of familial spastic paraparesis (spastic paraplegia 2 [SPG2]) are X-linked development disorders of myelin formation caused by a mutation in the proteolipid protein (PLP) gene. Spastic paraplegia 2 is allelic to PMD. The wide range of PLP mutations results in a corresponding large spectrum of clinical severity in PMD, with a continuum of signs and symptoms to SPG2. Objective: To report the results of genetic, neurophysiologic, and neuroimaging investigations performed in a child affected by a mild ataxic and spastic form of PLP-related disorder and in his relatives. Results: A missense mutation in exon 6 of the PLP gene (Q233P) was found in the proband and in the female obligate carriers. In the proband, evoked potentials were altered and remained unchanged during the 7 years of follow-up. Magnetic resonance imaging of the child demonstrated patchy hyperintensities of the paraventricular white matter, with microcystic components. These latter findings, along with pallidal calcium deposition, were also present in 2 females heterozygous for PLP mutation. Conclusion: The unusual genetic, magnetic resonance imaging, and clinical findings of this family confirm the wide variability of PLP-related disorders.