Inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD) is caused by mutations in the valosin-containing protein (VCP) gene. Varied clinical features caused by
VCP mutations have been reported: these clinical phenotypes include distal myopathy, frontotemporal dementia and amyotrophic lateral sclerosis. We report a 49-year-old woman with 3-year history of progressive proximal limb muscle weakness. Family history was notable for her father with motor neuron disease and an elder brother with a myopathy involving tibialis anterior and quadriceps. Neurological examinations showed proximal muscle atrophy, especially severe atrophy of paravertebral muscles, right-dominant scapular winging, bilateral pyramidal signs and hyperreflexia. Serum CK level was normal and EMG showed chronic neurogenic changes. Muscle imaging (CT) showed adipose tissue replacement of paravertebral muscles and right serratus anterior, and marked atrophy of bilateral trapezius and vastus intermedius muscles. Her lumbar spine X-ray showed an osteosclerotic change in the vertebral body, where an increased uptake of Tc99m was also observed in bone scintigraphy. Although brain MRI was normal, neuropsychological examination showed a mild attention deficit with cognitive impairment. A muscle biopsy specimen revealed scattered fibers with rimmed vacuoles. These findings prompted us to analyze a mutation in the
VCP gene. Genomic sequencing of all exons of the gene showed a heterozygous missense mutation in exon 5 (c.1315G>C; p.Ala439Pro).
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