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Distinct distal myopathy phenotype caused by VCP gene mutation in a Finnish family

Johanna Palmio1, Satu Sandell, Tiina Suominen

  • 1Neuromuscular Research Unit, Department of Neurology, University Hospital and University of Tampere, Finland. johanna.palmio@uta.fi

Neuromuscular Disorders : NMD
|June 21, 2011
PubMed

Insights

Mutations in the valosin-containing protein (VCP) gene cause a rare distal myopathy. This VCP gene mutation presents with leg weakness and can lead to dementia, requiring consideration in differential diagnoses.

Area of Science:

  • Genetics
  • Neurology
  • Molecular Biology

Background:

  • Inclusion body myopathy with Paget disease and frontotemporal dementia (IBMPFD) is linked to mutations in the valosin-containing protein (VCP) gene.
  • The VCP gene's role in neuromuscular and neurodegenerative disorders is increasingly recognized.

Purpose of the Study:

  • To report a novel distal phenotype associated with VCP gene mutations in a Finnish family.
  • To highlight the diagnostic challenges and clues for identifying VCP-related myopathies.

Main Methods:

  • Clinical evaluation of nine affected family members across three generations.
  • Phenotypic analysis including muscle weakness, atrophy, and neurological progression.
  • Genetic analysis to identify the specific VCP gene mutation (P137L, c.410C>T).

Main Results:

  • A distinct distal myopathy phenotype characterized by adult-onset anterior compartment leg muscle weakness and foot drop was observed.
  • Affected individuals did not exhibit proximal myopathy, scapular winging, or cardiac/respiratory issues.
  • A subset of patients developed rapidly progressive dementia, cachexia, and pneumonia, leading to mortality.
  • The P137L mutation in the VCP gene was identified as the causative genetic factor.

Conclusions:

  • VCP gene mutations can manifest as a late-onset autosomal dominant distal myopathy with unique clinical features.
  • The presence of dementia is a critical diagnostic clue for VCP-related disorders, even in the absence of typical IBMPFD symptoms.
  • VCP should be considered in the differential diagnosis of patients presenting with distal myopathy, particularly when accompanied by neurological decline.

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