Sporadic late-onset nemaline myopathy: clinico-pathological characteristics and review of 76 cases
Abstract Background Sporadic late-onset nemaline myopathy (SLONM) is a rare, late-onset muscle disorder, characterized by the presence of nemaline rods in muscle fibers. Phenotypic characterization in a large cohort and a comprehensive overview of SLONM are lacking. Methods We studied the clinico-pa...
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| Language: | English |
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BMC
2017-05-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | http://link.springer.com/article/10.1186/s13023-017-0640-2 |
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| author | Lukas J. Schnitzler Tobias Schreckenbach Aleksandra Nadaj-Pakleza Werner Stenzel Elisabeth J. Rushing Philip Van Damme Andreas Ferbert Susanne Petri Christian Hartmann Antje Bornemann Andreas Meisel Jens A. Petersen Thomas Tousseyn Dietmar R. Thal Jens Reimann Peter De Jonghe Jean-Jacques Martin Peter Y. Van den Bergh Jörg B. Schulz Joachim Weis Kristl G. Claeys |
| author_facet | Lukas J. Schnitzler Tobias Schreckenbach Aleksandra Nadaj-Pakleza Werner Stenzel Elisabeth J. Rushing Philip Van Damme Andreas Ferbert Susanne Petri Christian Hartmann Antje Bornemann Andreas Meisel Jens A. Petersen Thomas Tousseyn Dietmar R. Thal Jens Reimann Peter De Jonghe Jean-Jacques Martin Peter Y. Van den Bergh Jörg B. Schulz Joachim Weis Kristl G. Claeys |
| author_sort | Lukas J. Schnitzler |
| collection | DOAJ |
| description | Abstract Background Sporadic late-onset nemaline myopathy (SLONM) is a rare, late-onset muscle disorder, characterized by the presence of nemaline rods in muscle fibers. Phenotypic characterization in a large cohort and a comprehensive overview of SLONM are lacking. Methods We studied the clinico-pathological features, treatment and outcome in a large cohort of 76 patients with SLONM, comprising 10 new patients and 66 cases derived from a literature meta-analysis (PubMed, 1966–2016), and compared these with 15 reported HIV-associated nemaline myopathy (HIV-NM) cases. In 6 SLONM patients, we performed a targeted next-generation sequencing (NGS) panel comprising 283 myopathy genes. Results SLONM patients had a mean age at onset of 52 years. The predominant phenotype consisted of weakness and atrophy of proximal upper limbs in 84%, of proximal lower limbs in 80% and both in 67%. Other common symptoms included axial weakness in 68%, as well as dyspnea in 55% and dysphagia in 47% of the patients. In 53% a monoclonal gammopathy of unknown significance (MGUS) was detected in serum. The mean percentage of muscle fibers containing rods was 28% (range 1–63%). In 2 cases ultrastructural analysis was necessary to detect the rods. The most successful treatment in SLONM patients (all with MGUS) was autologous peripheral blood stem cell therapy. A targeted NGS gene panel in 6 SLONM patients (without MGUS) did not reveal causative pathogenic variants. In a comparison of SLONM patients with and without MGUS, the former comprised significantly more males, had more rapid disease progression, and more vacuolar changes in muscle fibers. Interestingly, the muscle biopsy of 2 SLONM patients with MGUS revealed intranuclear rods, whereas this feature was not seen in any of the biopsies from patients without paraproteinemia. Compared to the overall SLONM cohort, significantly more HIV-NM patients were male, with a lower age at onset (mean 34 years). In addition, immunosuppression was more frequently applied with more favorable outcome, and muscle biopsies revealed a significantly higher degree of inflammation and necrosis in this cohort. Similar to SLONM, MGUS was present in half of the HIV-NM patients. Conclusions SLONM presents a challenging, but important differential diagnosis to other neuromuscular diseases of adult onset. Investigations for MGUS and HIV should be performed, as they require distinct but often effective therapeutic approaches. Even though SLONM and HIV-NM show some differences, there exists a large clinico-pathological overlap between the 2 entities. |
| first_indexed | 2024-12-11T00:20:05Z |
| format | Article |
| id | doaj.art-d683de3e2eeb4e0290c805d869e0301b |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-11T00:20:05Z |
| publishDate | 2017-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-d683de3e2eeb4e0290c805d869e0301b2022-12-22T01:27:47ZengBMCOrphanet Journal of Rare Diseases1750-11722017-05-0112111210.1186/s13023-017-0640-2Sporadic late-onset nemaline myopathy: clinico-pathological characteristics and review of 76 casesLukas J. Schnitzler0Tobias Schreckenbach1Aleksandra Nadaj-Pakleza2Werner Stenzel3Elisabeth J. Rushing4Philip Van Damme5Andreas Ferbert6Susanne Petri7Christian Hartmann8Antje Bornemann9Andreas Meisel10Jens A. Petersen11Thomas Tousseyn12Dietmar R. Thal13Jens Reimann14Peter De Jonghe15Jean-Jacques Martin16Peter Y. Van den Bergh17Jörg B. Schulz18Joachim Weis19Kristl G. Claeys20Department of Neurology, University Hospital RWTH AachenDepartment of Neurology, Medizinisches Zentrum StädteRegion AachenReference Centre for Neuromuscular Diseases, Department of Neurology, University Hospital AngersDepartment of Neuropathology, Charité - Universitätsmedizin BerlinInstitute of Neuropathology, University Hospital ZürichDepartment of Neurology, University Hospitals LeuvenDepartment of Neurology, Klinikum KasselDepartment of Neurology, Hannover Medical SchoolDepartment of Neuropathology, Hannover Medical SchoolInstitute of Neuropathology, University Hospital TübingenDepartment of Neurology, University Hospital Charité BerlinDepartment of Neurology, University Hospital Zurich and University of ZurichDepartment of Pathology, University Hospitals LeuvenDepartment of Pathology, University Hospitals LeuvenDepartment of Neurology, University Hospital BonnDepartment of Neurology, University Hospital AntwerpenBorn-Bunge Institute, University of AntwerpenDepartment of Neurology, University Hospital Saint-LucDepartment of Neurology, University Hospital RWTH AachenInstitute of Neuropathology, University Hospital RWTH AachenDepartment of Neurology, University Hospital RWTH AachenAbstract Background Sporadic late-onset nemaline myopathy (SLONM) is a rare, late-onset muscle disorder, characterized by the presence of nemaline rods in muscle fibers. Phenotypic characterization in a large cohort and a comprehensive overview of SLONM are lacking. Methods We studied the clinico-pathological features, treatment and outcome in a large cohort of 76 patients with SLONM, comprising 10 new patients and 66 cases derived from a literature meta-analysis (PubMed, 1966–2016), and compared these with 15 reported HIV-associated nemaline myopathy (HIV-NM) cases. In 6 SLONM patients, we performed a targeted next-generation sequencing (NGS) panel comprising 283 myopathy genes. Results SLONM patients had a mean age at onset of 52 years. The predominant phenotype consisted of weakness and atrophy of proximal upper limbs in 84%, of proximal lower limbs in 80% and both in 67%. Other common symptoms included axial weakness in 68%, as well as dyspnea in 55% and dysphagia in 47% of the patients. In 53% a monoclonal gammopathy of unknown significance (MGUS) was detected in serum. The mean percentage of muscle fibers containing rods was 28% (range 1–63%). In 2 cases ultrastructural analysis was necessary to detect the rods. The most successful treatment in SLONM patients (all with MGUS) was autologous peripheral blood stem cell therapy. A targeted NGS gene panel in 6 SLONM patients (without MGUS) did not reveal causative pathogenic variants. In a comparison of SLONM patients with and without MGUS, the former comprised significantly more males, had more rapid disease progression, and more vacuolar changes in muscle fibers. Interestingly, the muscle biopsy of 2 SLONM patients with MGUS revealed intranuclear rods, whereas this feature was not seen in any of the biopsies from patients without paraproteinemia. Compared to the overall SLONM cohort, significantly more HIV-NM patients were male, with a lower age at onset (mean 34 years). In addition, immunosuppression was more frequently applied with more favorable outcome, and muscle biopsies revealed a significantly higher degree of inflammation and necrosis in this cohort. Similar to SLONM, MGUS was present in half of the HIV-NM patients. Conclusions SLONM presents a challenging, but important differential diagnosis to other neuromuscular diseases of adult onset. Investigations for MGUS and HIV should be performed, as they require distinct but often effective therapeutic approaches. Even though SLONM and HIV-NM show some differences, there exists a large clinico-pathological overlap between the 2 entities.http://link.springer.com/article/10.1186/s13023-017-0640-2SLONMMuscle biopsyHIV-associated nemaline myopathyHIV-NMMonoclonal gammopathyMGUS |
| spellingShingle | Lukas J. Schnitzler Tobias Schreckenbach Aleksandra Nadaj-Pakleza Werner Stenzel Elisabeth J. Rushing Philip Van Damme Andreas Ferbert Susanne Petri Christian Hartmann Antje Bornemann Andreas Meisel Jens A. Petersen Thomas Tousseyn Dietmar R. Thal Jens Reimann Peter De Jonghe Jean-Jacques Martin Peter Y. Van den Bergh Jörg B. Schulz Joachim Weis Kristl G. Claeys Sporadic late-onset nemaline myopathy: clinico-pathological characteristics and review of 76 cases Orphanet Journal of Rare Diseases SLONM Muscle biopsy HIV-associated nemaline myopathy HIV-NM Monoclonal gammopathy MGUS |
| title | Sporadic late-onset nemaline myopathy: clinico-pathological characteristics and review of 76 cases |
| title_full | Sporadic late-onset nemaline myopathy: clinico-pathological characteristics and review of 76 cases |
| title_fullStr | Sporadic late-onset nemaline myopathy: clinico-pathological characteristics and review of 76 cases |
| title_full_unstemmed | Sporadic late-onset nemaline myopathy: clinico-pathological characteristics and review of 76 cases |
| title_short | Sporadic late-onset nemaline myopathy: clinico-pathological characteristics and review of 76 cases |
| title_sort | sporadic late onset nemaline myopathy clinico pathological characteristics and review of 76 cases |
| topic | SLONM Muscle biopsy HIV-associated nemaline myopathy HIV-NM Monoclonal gammopathy MGUS |
| url | http://link.springer.com/article/10.1186/s13023-017-0640-2 |
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