Bethlem myopathy: Early-onset benign autosomal dominant myopathy with contractures. Description of two new families

Merlini, Luciano; Morandi, Lucia; Granata, Claudia; Ballestrazzi, A.

doi:10.1016/0960-8966(94)90091-4

Cited by 70 publications

(55 citation statements)

References 21 publications

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“…26,27 Mice with targeted disruption of the Col6a1 gene display a muscle phenotype that strongly resembles Bethlem myopathy. 5,30 Col6a1 Ϫ/Ϫ muscles have a loss of contractile strength associated with ultrastructural alterations, consisting of marked dilations of the sarcoplasmic reticulum (SR), and of mitochondrial alterations that ranged from tubular cristae, to electron-dense inclusions, to overt swelling. 27 Remarkably, myofibers with mitochondrial-SR alterations also displayed nuclear features of apoptosis, suggesting a link between organellar changes and increased incidence of cell death.…”

Section: The Collagen Vi-mitochondria Connectionmentioning

confidence: 99%

“…4 Bethlem myopathy is an autosomal dominant disorder characterized by slowly progressive axial and proximal muscle weakness with finger flexion contractures. 5 Bethlem myopathy shows interfamilial variability and different clinical onset, from prenatal to mid-adulthood. Prenatal onset is characterized by decreased fetal movements; neonatal onset with hypotonia or torticollis; early-childhood onset with delayed motor milestones and muscle weakness and contractures; and adult onset with proximal weakness, and Achilles tendon and finger contractures.…”

Section: Introductionmentioning

confidence: 99%

“…Prenatal onset is characterized by decreased fetal movements; neonatal onset with hypotonia or torticollis; early-childhood onset with delayed motor milestones and muscle weakness and contractures; and adult onset with proximal weakness, and Achilles tendon and finger contractures. Bethlem myopathy is usually mild, 5 sometimes slowly progressive, with some affected individuals over 50 years of age needing aids for mobility outdoors. 6 There is no evidence of cardiac involvement in BM.…”

Section: Introductionmentioning

confidence: 99%

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Therapy of Collagen VI-Related Myopathies (Bethlem and Ullrich)

Merlini

Bernardi

2008

Neurotherapeutics

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Summary:The collagen VI-related myopathies comprise two major forms, Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD), which show a variable combination of muscle wasting and weakness, joint contractures, distal laxity, and respiratory compromise. Specific diagnosis requires molecular genetic testing showing mutation in one of the three genes involved. This review summarizes current treatments, in particular indication for physiotherapy, orthopedic treatment for correction of foot deformity, scoliosis, and flexion contractures of elbows, and treatment of respiratory failure. The turning point in basic research on collagen VI myopathies was the discovery of an unexpected mitochondrial dysfunction as a pathogenetic mechanism underlying the myopathic syndrome seen in Col6a1 null mice. Treatment of Col6a1 Ϫ/Ϫ mice with cyclosporin A (CsA) rescued the mitochondrial dysfunction and decreased apoptosis. Similar mitochondrial defects were revealed in cultures of UCMD patients. The results of an open pilot trial with CsA in five patients with collagen VIrelated myopathies are summarized and discussed. With the availability of new potential effective treatments, several challenges must be addressed in conducting trials in orphan diseases and in neuromuscular disorders in particular. Outcome measures are discussed in the context of the expected effect of the cure. Randomized clinical trials often are not feasible for rare diseases, and sometimes would be ethically inappropriate. The need to develop alternative outcome measures or biomarkers using platforms such as genomics and proteomics is stressed in this context.

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Section: The Collagen Vi-mitochondria Connectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Therapy of Collagen VI-Related Myopathies (Bethlem and Ullrich)

Merlini

Bernardi

2008

Neurotherapeutics

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“…Bethlem myopathy (OMIM # 158810) is an early-onset benign myopathy characterized by proximal muscle weakness and multiple flexion contractures [1][2][3]. It is caused by dominant mutations in COL6A1 (OMIM # 120220), COL6A2 (OMIM # 120240) [4], and COL6A3 (OMIM # 120250) [5] genes.…”

Section: Introductionmentioning

confidence: 99%

Bethlem myopathy (BETHLEM) and Ullrich scleroatonic muscular dystrophy: 100th ENMC International Workshop, 23–24 November 2001, Naarden, The Netherlands

Pepe

Bertini

Bonaldo

et al. 2002

Neuromuscular Disorders

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“…In addition to electromyography and muscle biopsy, Xray computed tomography (CT) is often used to diagnose muscle disease in humans [1,2,3,5,7] because morphological changes can be observed noninvasively even in deep muscles [4,7,9,10]. However, CT has not been used to diagnose muscle disease in veterinary medicine.…”

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confidence: 99%

Computed Tomographic Findings of Experimentally Induced Neurogenic Muscular Atrophy in Dogs.

Orima

Fujita

1997

The Journal of Veterinary Medical Science

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ABSTRACT. Neurogenic muscular atrophy was examined using computed tomography (CT) in dogs induced by crushing the sciatic nerve. The CT number and cross-sectional area in denervated muscles decreased in 1 to 2 weeks after denervation. Those were significant after 3 weeks. The examination with CT might be useful to diagnose canine neurogenic muscular atrophy. -KEY WORDS: canine, CT, muscle atrophy.J. Vet. Med. Sci. 59(8): 729-731, 1997 window level and width were set at 50 HU and 250 HU respectively. CT images were also evaluated under the other conditions in necessary. We observed well-defined biceps, semimembranosus, and semitendinosus, in comparison with the quadriceps innervated by the femoral nerve and the adductor innervated by the obturator nerve as controls. CT numbers were measured at three arbitrarily chosen regions for each muscle, and the mean values were regarded as the CT number for that muscle. The cross-sectional area of each muscle was measured, using an area-measurement program of CT unit by manually tracing the muscle margin on the CT image. The crosssectional area of the femoral bone was measured likewise, and the cross-sectional area of a muscle was expressed as its ratio to the cross-sectional area of the femoral bone.On day 28, the semitendinosus muscle in one dog was taken from a region which would not influence subsequent CT examination. The sample was examined histopathologically.All procedures were conducted according to the Guidelines for the Care and Use of Laboratory Animals of The Nippon Veterinary and Animal Science University. Within eight months after the end of the experiment, the dogs showed no neurologic abnormality in the affected leg.CT images showed decreases in CT number and muscle cross-sectional areas (Fig. l). Before denervation CT numbers (HU) of muscles were 58.4 ± 2.2 for the biceps, 56.0 ± 1.8 for the semimembranosus, 50.0 ± 3.2 for the semitendinosus, 57.8 ± 3.7 for the quadriceps, and 58.7 ± 2.1 for the adductor. The semitendinosus was difficult to be measured accurately because of its small cross-sectional area. In the three muscles innervated by the sciatic nerve CT numbers increased on day 1, and then tended to decrease from day 14 after surgery, continuing to decrease relatively rapidly until day 28. A slight further decrease was observed thereafter with minimum values on day 56 (Fig. 2).The cross-sectional areas of the muscles were measured on the CT images before denervation. The ratios to the cross-sectional area of the femoral bone were 6.8 ± 1.6 for the biceps, 5.5 ± 1.8 for the semimembranosus, 2.7 ± 1.6 for the semitendinosus, 6.2 ± 1.7 for the quadriceps, and 11.2 ± 3

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Bethlem myopathy: Early-onset benign autosomal dominant myopathy with contractures. Description of two new families

Cited by 70 publications

References 21 publications

Therapy of Collagen VI-Related Myopathies (Bethlem and Ullrich)

Therapy of Collagen VI-Related Myopathies (Bethlem and Ullrich)

Bethlem myopathy (BETHLEM) and Ullrich scleroatonic muscular dystrophy: 100th ENMC International Workshop, 23–24 November 2001, Naarden, The Netherlands

Computed Tomographic Findings of Experimentally Induced Neurogenic Muscular Atrophy in Dogs.

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