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

Neuromuscul Disord. 2011 Aug;21(8):551-5. doi: 10.1016/j.nmd.2011.05.008.

Abstract

Inclusion body myopathy with Paget disease and frontotemporal dementia (IBMPFD) is caused by mutations in the valosin-containing protein (VCP) gene. We report a new distal phenotype caused by VCP gene mutation in a Finnish family with nine affected members in three generations. Patients had onset of distal leg muscle weakness and atrophy in the anterior compartment muscles after age 35, which caused a foot drop at age 50. None of the siblings had scapular winging, proximal myopathy, cardiomyopathy or respiratory problems during long-term follow-up. Three distal myopathy patients developed rapidly progressive dementia, became bedridden and died of cachexia and pneumonia and VCP gene mutation P137L (c.410C>T) was then identified in the family. Late onset autosomal dominant distal myopathy with rimmed vacuolar muscle pathology was not sufficient for exact diagnosis in this family until late-occurring dementia provided the clue for molecular diagnosis. VCP needs to be considered in the differential diagnostic work-up in patients with distal myopathy phenotype.

MeSH terms

  • Adenosine Triphosphatases / genetics*
  • Adult
  • Cell Cycle Proteins / genetics*
  • Diagnosis, Differential
  • Distal Myopathies / diagnosis
  • Distal Myopathies / ethnology*
  • Distal Myopathies / genetics*
  • Female
  • Finland
  • Humans
  • Male
  • Middle Aged
  • Muscular Dystrophies / diagnosis
  • Mutation / genetics*
  • Pedigree
  • Phenotype*
  • Valosin Containing Protein

Substances

  • Cell Cycle Proteins
  • Adenosine Triphosphatases
  • VCP protein, human
  • Valosin Containing Protein