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.


CONCLUSIONS
The unusual genetic, magnetic resonance imaging, and clinical findings of this family confirm the wide variability of PLP-related disorders.
Battini
Roberta
R
Division of Child Neurology and Psychiatry, Instituto di Recovero e Cura a Carattere Scientifico Stella Maris, Pisa, Italy.
Bianchi
M Cristina
MC
Boespflug-Tanguy
Odile
O
Tosetti
Michela
M
Bonanni
Paolo
P
Canapicchi
Raffaello
R
Cioni
Giovanni
G
D000328:Adult; D001921:Brain / Q000473:pathology*; D002648:Child; D005071:Evoked Potentials; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D018991:Myelin Proteolipid Protein / Q000235:genetics*; D010375:Pedigree; D020371:Pelizaeus-Merzbacher Disease / Q000235:genetics* / Q000473:pathology*
D018991:Myelin Proteolipid Protein