Only three facioscapulohumeral muscular dystrophy (FSHD) patients have been reported to have cardiomyopathy. An asymptomatic 38-year-old man was incidentally found to have electrocardiographic abnormalities. His echocardiogram demonstrated mild dilatation of the left ventricle and poor contractility. Cardiac histopathology indicated hypertrophic cardiomyopathy. Later he developed muscle weakness in the right arm. Scapular winging and asymmetrical facial weakness were evident. Muscle biopsy at the age of 44 years showed myopathic changes consistent with FSHD. His daughter had symptoms of infantile FSHD, which was genetically confirmed. This is the first report of an FSHD patient with biopsy-proven cardiomyopathy.
"Most of these pathways have already been described in FSHD: apoptosis (Kowaljow et al., 2007),oxidative phosphorylation (Turki et al., 2012), leukocyte transendothelial migration (Frisullo et al., 2011; Rahimov et al., 2012), regulation of actin cytoskeleton (Dmitriev et al., 2011b; Rahimov et al., 2012; Tassin et al., 2012), calcium signaling pathway (Rahimov et al., 2012), cardiac muscle contraction (Rahimov et al., 2012) and vascular smooth muscle creation (Osborne et al., 2007). Others have been reported to be associated to FSHD patients like hypertrophic cardiomyopathy (Tsuji et al., 2009) and cancer (Dmitriev et al., 2014). In hybrid myotubes, the number of affected pathways was reduced when the proportion of normal myoblasts increased in the initial cell culture, from 39 in 100% FSHD myotubes to five, two and one in mixtures "
[Show abstract][Hide abstract] ABSTRACT: Facioscapulohumeral dystrophy (FSHD) is a neuromuscular disease with a prevalence that could reach 1 in 8,000 characterized by progressive asymmetric muscle weakness. Myoblasts isolated from FSHD muscles exhibit morphological differentiation defects and show a distinct transcription profile. These abnormalities may be linked to the muscle weakness in FSHD patients. We have tested whether fusion of FSHD myoblasts with primary myoblasts isolated from healthy individuals could correct the differentiation defects. Our results show that the number of hybrid myotubes with normal phenotype increased with the percentage of normal myoblasts initially cultured. We demonstrated that a minimum of 50% of normal nuclei is required for a phenotypic correction of the FSHD phenotype. Moreover, transcriptomic profiles of phenotypically corrected hybrid myotubes showed that the expression of deregulated genes in FSHD myotubes became almost normal. The number of deregulated pathways also decreased from 39 in FSHD myotubes to one in hybrid myotubes formed with 40% FSHD and 60% normal myoblasts. We thus propose that while phenotypical and functional correction of FSHD is feasible, it requires more than 50% of normal myoblasts, it creates limitations for cell therapy in the FSHD context. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Journal of Cellular Physiology 07/2015; DOI:10.1002/jcp.25110 · 3.84 Impact Factor
"The extensive use of the molecular analysis as diagnostic test in human hereditary myopathies has led to the identification of an increasing number of atypical phenotypes. This is particularly true for FSHD, in which various clinical features have been found in subjects carrying FSHD-sized D4Z4 alleles, including a facial-sparing form of FSHD (SHD) , limb-girdle muscular dystrophy , distal myopathy , asymmetric brachial weakness , chronic progressive external ophthalmoplegia , asymptomatic hyperCKemia , hypertrophic cardiomyopathy , adult-onset distal myopathies with rimmed vacuoles , isolated axial myopathy with camptocormia and bent spine syndrome [49,50]. In addition, overlapping FSHD phenotypes in which 4q35 deleted D4Z4 mutation is associated with other pathogenic mutations in other genes, have been reported in cases of patients with mitochondrial myopathy/FSHD , Becker dystrophy/FSHD , Duchenne dystrophy/FSHD [53,54], Leber’s hereditary optic neuropathy/FSHD , suggesting a synergistic effect of those simultaneous mutations in reaching disease threshold and determining overlapping phenotypes. "
[Show abstract][Hide abstract] ABSTRACT: We report the first case of a heterozygous T78M mutation in the caveolin-3 gene (CAV3) associated with rippling muscle disease and proximal myopathy. The patient displayed also bilateral winged scapula with limited abduction of upper arms and marked asymmetric atrophy of leg muscles shown by magnetic resonance imaging. Immunohistochemistry on the patient's muscle biopsy demonstrated a reduction of caveolin-3 staining, compatible with the diagnosis of caveolinopathy. Interestingly, consistent with the possible diagnosis of FSHD, the patient carried a 35 kb D4Z4 allele on chromosome 4q35. We discuss the hypothesis that the two genetic mutations may exert a synergistic effect in determining the phenotype observed in this patient.
[Show abstract][Hide abstract] ABSTRACT: Facioscapulohumeral muscular dystrophy (FSHD) is the third most common muscular dystrophy and usually follows an autosomal dominant trait. Clinically, FSHD affects facial muscles and proximal upper limb and girdle muscles, but may present with variable clinical phenotypes even within the same family. Most genetically confirmed FSHD patients exhibit unspecific morphological signs of a degenerative myopathy. We report on five unrelated patients who carried the pathogenic FSHD mutation on chromosome 4q35. Muscle biopsies revealed numerous rimmed vacuoles and filamentous cytoplasmic inclusions in all cases. Clinically, the patients suffered from weakness and atrophy predominantly of the lower limb muscles. In conclusion, we suggest considering FSHD in the differential diagnosis of adult-onset distal myopathies with rimmed vacuoles.
Journal of Neurology 02/2010; 257(7):1108-18. DOI:10.1007/s00415-010-5471-1 · 3.38 Impact Factor
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