Résumé :
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Background : Hereditary inclusion body myopathy with Paget disease of bone (PDB) and frontotemporal dementia (FTD), or IBMPDF disease, is an autosomal dominant disorder related to mutations in Valosin-containing protein (VCP). Objective: The aim of the study was to describe the clinical, pulmonary, cardiac and histopathological features of 19 patients presenting an IBMPDF disease associated with mutations in the VCP gene. Material and methods: PDB was investigated on standard X-rays, bone scintigraphy and alkaline phosphatase dosage. Cognitive impairment was assayed on clinical data and neuropsychological tests. Immunohistochemical studies were performed in biopsies using antibodies directed against dystrophin, sarcoglycans, merosin, dysferlin, alpha-dystroglycan, and desmin. Genetic diagnosis was obtained by direct sequencing of the 17 coding exons of VCP gene. Results: The age at onset ranges from 20 to 62 years old. The clinical pattern was characterized by an early involvement of proximal upper limb with scapular winging. Axial and distal muscles of lower limbs were often and early affected, whereas facial, oculobulbar muscles were spared. Ten patients were wheelchair-bound and 4 patients required aid for walking. Two patients required mechanical assisted ventilation and 7 patients had reduced vital capacity. There was no cardiac involvement. Paget disease was observed in 8 patients. Cognitive dysfunction was observed in 9 cases. Seven patients died as the consequence of weakness and respiratory distress. Muscle biopsy revealed rimmed vacuolar myopathy and genetic analysis revealed heterozygous missense mutations in VCP gene in all patients. Conclusion: In our series of 19 cases with IBMPDF disease, we observed an intra-familial variability in terms of severity, distribution of weakness and presence or absence of Paget disease or cognitive impairment.
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