Clinical outcome in 19 French and Spanish patients with valosin-containing protein myopathy associated with Paget's disease of bone and frontotemporal dementia.
We report the clinical, histological and genetic findings in 10 families (19 patients) presenting mutations in the valosin-containing protein (VCP). The mean age at onset was 42 years. The clinical pattern was characterized by an early involvement of the proximal upper limbs with scapular winging. Axial and lower limb muscles were often affected, whereas facial, oculobulbar muscles were spared. Ten patients were wheelchair bound after a mean disease course of 9 years and six patients required canes for walking. Two patients required mechanically assisted ventilation and seven patients had reduced vital capacity. There was no cardiac involvement. Paget's disease of bone was observed in eight patients and cognitive impairment in nine patients. Seven patients died as a consequence of weakness and respiratory distress. Muscle biopsy showed rimmed vacuolar myopathy. Genetic analysis revealed missense heterozygous mutations mostly located in exon 5 of the VCP gene, four of which were not previously reported. We observed intrafamilial and interfamilial variability in terms of severity, distribution of weakness and presence or not of Paget's disease or cognitive impairment.
AP-HP, Institute of Myology, G-H Pitié-Salpêtrière, Paris, France. Tanya.Stojkovic@psl.aphp.fr
Tanya
T
Stojkovic
El Hadi
el H
Hammouda
Pascale
P
Richard
Adolfo
A
López de Munain
Javier
J
Ruiz-Martinez
Pilar
P
Camaño
Pilar Camaño
PC
Gonzalez
Pascal
P
Laforêt
Isabelle
I
Pénisson-Besnier
Xavier
X
Ferrer
Arnaud
A
Lacour
Lucette
L
Lacomblez
Kristl G
KG
Claeys
Claude-Alain
CA
Maurage
Michel
M
Fardeau
Bruno
B
Eymard
D000251:Adenosine Triphosphatases / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins / Q000235:genetics*; D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D004252:DNA Mutational Analysis; D003704:Dementia / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005121:Extremities / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005602:France; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D020125:Mutation, Missense / Q000235:genetics; D018979:Myositis, Inclusion Body / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D010001:Osteitis Deformans / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype; D012133:Respiratory Paralysis / Q000235:genetics / Q000503:physiopathology; D013030:Spain; D000074405:Valosin Containing Protein
D018797:Cell Cycle Proteins; D005819:Genetic Markers; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein