Camptocormia In A Patient With Valosin-Containing Protein (Vcp) Mutation

OBJECTIVE: To report a novel clinical presentation, pathological findings, and genetic analysis of a patient with VCP related myopathy. BACKGROUND: Inclusion body myopathy associated with Paget9s disease of the bone (PBD) and frontotemporal dementia, or IBMPFD, is a multisystem degenerative disorder due to mutations in the VCP gene. Penetrance of the disease features is variable. Various patterns of muscle involvement have been described. Camptocormia may be attributed to central or peripheral nervous system disorders. To our knowledge, camptocormia has not been reported in IBMPFD. DESIGN/METHODS: Retrospective review of medical records, muscle biopsy, and genetic analysis. RESULTS: A 39 year old man presented with five years of progressive lower extremity weakness and need of walking bent over. For 2 years he had difficulties raising arms above his shoulders. There was a history of ALS in his mother, and myopathy in maternal grandmother, mother9s uncle, and mother9s sister. Clinical evaluation was significant for obesity, bifacial weakness, bilateral scapular winging and camptocormia. On strength examination, elbow and hip flexors were (R/L) 4-/4-; knee extensors, 4/5-; knee flexors, 4/4; elsewhere strength was 5/5. EMG showed fibrillations in upper and lower extremities proximal and distal muscles, myotonic discharges in the cervical paraspinal, biceps, and medial gastrocnemius muscles, and myopathic motor units more in proximal versus distal muscles. Biopsy of the quadriceps showed a severe myopathy with rimmed vacuoles and intranuclear and cytoplasmic IBM-type tubulofilamentous inclusions. CK varied from 1700 to 2,000 U/L (normal 49-397). PFT showed restrictive pattern. Plain thoracolumbar films showed minimal degenerative changes. Alkaline phosphatase was normal. FSHD genetic test was negative. Sequencing of the VCP gene revealed disease-causing heterozygous mutations: Exon 5, c.572G>A, resulting in p.Arg191Gln. CONCLUSIONS: Notable clinical features in this patient included scapulohumeral and proximal lower extremity weakness and camptocormia. At this time, FTD or PBD are not present. Disclosure: Dr. Fernandes has nothing to disclose. Dr. Oskarsson has received personal compensation for activities with Avanir Pharmaceuticals as a speaker. Dr. Thaisetthawatkul has nothing to disclose. Dr. McComb has nothing to disclose.