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Background <p>Pathogenic <i>VCP</i> gene mutations cause inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD), a rare autosomal dominant disorder marked by high heterogeneity and incomplete penetrance, complicating diagnosis.</p> Case description <p>We present a genetically and pathologically confirmed IBMPFD case with 11-year follow-up and pedigree analysis. The proband experienced muscle weakness and atrophy starting at age 43, initially misdiagnosed as motor neuron disease. At 49, a muscle biopsy showed rimmed vacuoles, and genetic testing confirmed IBMPFD with a <i>VCP</i> gene mutation (c.463C &gt; T, p.R155C). By the age of 53, the proband had developed symptoms of frontotemporal dementia, while no signs associated with Paget's disease were observed throughout the entire follow-up period. The proband’s 93-year-old mother was an asymptomatic carrier of the same mutation, highlighting phenotypic heterogeneity and incomplete penetrance.</p> Conclusions <p>This case study highlights unusual clinical and electrophysiological features and familial incomplete penetrance in IBMPFD, broadening the disorder's clinical and genetic understanding. Adults with slowly progressive myopathy, neurogenic electrophysiological changes, or cognitive-behavioral issues should be evaluated for IBMPFD, even without typical bone disease or family history. Early muscle biopsy and <i>VCP</i> genetic testing are essential to avoid misdiagnosis.</p>

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VCP-related inclusion body myopathy mimicking motor neuron disease with incomplete penetrance over 11 years of follow-up

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月20日

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  • Lanting Sun,
  • Daiping Hua,
  • Qiaoyu Xuan,
  • Wenming Yang,
  • Han Wang

摘要

Background

Pathogenic VCP gene mutations cause inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD), a rare autosomal dominant disorder marked by high heterogeneity and incomplete penetrance, complicating diagnosis.

Case description

We present a genetically and pathologically confirmed IBMPFD case with 11-year follow-up and pedigree analysis. The proband experienced muscle weakness and atrophy starting at age 43, initially misdiagnosed as motor neuron disease. At 49, a muscle biopsy showed rimmed vacuoles, and genetic testing confirmed IBMPFD with a VCP gene mutation (c.463C > T, p.R155C). By the age of 53, the proband had developed symptoms of frontotemporal dementia, while no signs associated with Paget's disease were observed throughout the entire follow-up period. The proband’s 93-year-old mother was an asymptomatic carrier of the same mutation, highlighting phenotypic heterogeneity and incomplete penetrance.

Conclusions

This case study highlights unusual clinical and electrophysiological features and familial incomplete penetrance in IBMPFD, broadening the disorder's clinical and genetic understanding. Adults with slowly progressive myopathy, neurogenic electrophysiological changes, or cognitive-behavioral issues should be evaluated for IBMPFD, even without typical bone disease or family history. Early muscle biopsy and VCP genetic testing are essential to avoid misdiagnosis.