<i>SEPN1</i>
            -related myopathies

Scoto, Mariacristina; Çırak, Sebahattin; Mein, R.; Feng, Lucy; Manzur, A.; Robb, Stephanie; Childs, Anne‐Marie; Quinlivan, R.; Roper, Helen; Jones, D. H.; Longman, Cheryl; Chow, Gabriel; Pane, Marika; Main, M.; Hanna, Michael G.; Bushby, Kate; Sewry, C.; Abbs, Stephen; Mercuri, Eugenio; Muntoni, Francesco

doi:10.1212/wnl.0b013e31821f467c

Cited by 79 publications

(77 citation statements)

References 20 publications

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“…5,33 We demonstrated that early-onset scoliosis is common, but usually mild and needing surgery only in 13.6% of all CMs. Half of all patients with scoliosis were ambulant at the time of surgery, suggesting that the development of scoliosis is more determined by early and disproportionate axial weakness 1,3,13 rather than ambulatory state.…”

Section: Methodsmentioning

confidence: 85%

“…In particular, failure to thrive and insidious respiratory insufficiency beyond the first year were observed in a substantial proportion, as reported in smaller series. 5,[13][14][15]19 It is often thought that children with CMs who achieve independent ambulation usually do not lose this ability later. 4 However, intermittent wheelchair use was needed in 22% of our ambulant patients, whereas 9% became completely wheelchairdependent within a few years, supporting observations of deterioration in muscle strength after the achievement of ambulation.…”

Section: Methodsmentioning

confidence: 99%

“…Indeed, cardiac involvement was rare, mainly right ventricle involvement associated with restrictive pulmonary impairment in SEPN1-mutated cases. 5,34 A relatively high incidence of talipes was observed mainly among patients with NM, most often with NEB mutation, reflecting distal involvement and genetic overlap between the NM and the distal arthrogryposis spectrum. We identified consistent genotype-phenotype correlations of relevance to clinical practice.…”

Section: Methodsmentioning

confidence: 99%

“…4 The natural history of specific subgroups has been described in only a few cohorts, not all of which had been fully genetically characterized. 5,[13][14][15][16][17][18][19] Herein, we report the clinical course of 125 patients with CM, reviewed at a single neuromuscular center. Furthermore, genotypephenotype correlations in a subgroup of 99 genetically characterized cases are illustrated.…”

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confidence: 99%

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Congenital myopathies

et al. 2015

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Objective: To assess the natural history of congenital myopathies (CMs) due to different genotypes. Methods:Retrospective cross-sectional study based on case-note review of 125 patients affected by CM, followed at a single pediatric neuromuscular center, between 1984 and 2012.Results: Genetic characterization was achieved in 99 of 125 cases (79.2%), with RYR1 most frequently implicated (44/125). Neonatal/infantile onset was observed in 76%. At birth, 30.4% required respiratory support, and 25.2% nasogastric feeding. Twelve percent died, mainly within the first year, associated with mutations in ACTA1, MTM1, or KLHL40. All RYR1-mutated cases survived and did not require long-term ventilator support including those with severe neonatal onset; however, recessive cases were more likely to require gastrostomy insertion (p 5 0.0028) compared with dominant cases. Independent ambulation was achieved in 74.1% of all patients; 62.9% were late walkers. Among ambulant patients, 9% eventually became wheelchairdependent. Scoliosis of variable severity was reported in 40%, with 1/3 of (both ambulant and nonambulant) patients requiring surgery. Bulbar involvement was present in 46.4% and required gastrostomy placement in 28.8% (at a mean age of 2.7 years). Respiratory impairment of variable severity was a feature in 64.1%; approximately half of these patients required nocturnal noninvasive ventilation due to respiratory failure (at a mean age of 8.5 years). Conclusions:We describe the long-term outcome of a large cohort of patients with CMs. While overall course is stable, we demonstrate a wide clinical spectrum with motor deterioration in a subset of cases. Severity in the neonatal/infantile period is critical for survival, with clear genotype-phenotype correlations that may inform future counseling. Neurology ® 2015;84:28-35 GLOSSARY ACTA1 5 skeletal muscle a-actin; AD 5 autosomal dominant; AR 5 autosomal recessive; CM 5 congenital myopathy; CNM 5 centronuclear myopathy; DNIV 5 daily noninvasive ventilation; DNM2 5 dynamin 2; FTD 5 fiber type disproportion; G/J 5 gastrostomy/jejunostomy; KLHL40 5 kelch-like family member 40; MTM1 5 myotubularin; NEB 5 nebulin; NGT 5 nasogastric tube; NM 5 nemaline myopathy; NNIV 5 nocturnal noninvasive ventilation; NSMC 5 nonspecific myopathic changes; RYR1 5 ryanodine receptor type 1; SEPN1 5 selenoprotein N; TPM2 5 b-tropomyosin; TPM3 5 tropomyosin 3.

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Section: Methodsmentioning

confidence: 85%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Congenital myopathies

et al. 2015

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“…SEPN1 gene mutations are associated with multiminicores, which are typically smaller in size than those associated with recessive RYR1 mutations [47], although there is a large histological spectrum associated with SEPN1 mutations that also includes nonspecific myopathic changes, CFTD, and Mallory body-like inclusions [61, 62]. Scoto et al [63] describe a large case series of patients with SEPN1 -related myopathies. Clinically, patients with SEPN1 -related disease manifest with a predominantly axial myopathy with weak neck flexors, spinal rigidity, and scoliosis, as well as prominent respiratory compromise disproportionate to their extremity weakness.…”

Section: Myopathies With Coresmentioning

confidence: 99%

Congenital Myopathies: An Update

Nance

Dowling

Gibbs

et al. 2012

Curr Neurol Neurosci Rep

109

101

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Congenital myopathy is a clinicopathological concept of characteristic histopathological findings on muscle biopsy in a patient with early-onset weakness. Three main categories are recognized within the classical congenital myopathies: nemaline myopathy, core myopathy, and centronuclear myopathy. Recent evidence of overlapping clinical and histological features between the classical forms and their different genetic entities suggests that there may be shared pathomechanisms between the congenital myopathies. Animal models, especially mouse and zebrafish, have been especially helpful in elucidating such pathomechanisms associated with the congenital myopathies and provide models in which future therapies can be investigated.

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Genetics of the Congenital Myopathies

Pelin¹

2021

Encyclopedia of Life Sciences

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The congenital myopathies are a heterogeneous group of skeletal muscle disorders characterised by muscle weakness present at birth and typical abnormalities in skeletal muscle fibres, such as protein aggregates, centrally located nuclei or areas lacking mitochondria. Mutations in more than 30 different genes can cause a congenital myopathy. The inheritance can be autosomal dominant, autosomal recessive or X‐linked or sporadic due to novel mutations. The mutated genes can be divided into three groups: genes encoding proteins of the skeletal muscle sarcomere, genes encoding proteins of the sarcoplasmic reticulum and transverse tubules and genes encoding proteins regulating muscle growth and regeneration. The mutations cause impaired or reduced muscle contraction by damaging the contractile machinery or by altering the regulation of muscle contraction, leading to muscle weakness. There is considerable clinical and histological overlap between the different types of congenital myopathies. The inheritance can be autosomal dominant, autosomal recessive or X‐linked or sporadic ( de novo mutations). Disease‐causing variants in more than 30 different genes can cause a congenital myopathy. Disease‐causing variants in the same gene can result in more than one clinical phenotype, and the same clinical phenotype can result from mutations in several different genes. The genes encode proteins essential for skeletal muscle development, muscle contraction, structure and protein turnover.

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SEPN1 -related myopathies

Cited by 79 publications

References 20 publications

Congenital myopathies

Congenital myopathies

Congenital Myopathies: An Update

Genetics of the Congenital Myopathies

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