J Rheum Dis.  2021 Apr;28(2):101-106. 10.4078/jrd.2021.28.2.101.

A Patient With Late-onset Limb-girdle Muscular Dystrophy Type 2B Mimicking Dermatomyositis: A Case Report and Review

• Kim MJ
• Oh YJ
• Hong YH
• Park SH
• Oh JS
• Kim MJ
• Chae JH
• Shin K

• KMID: 2514121
• DOI: http://doi.org/10.4078/jrd.2021.28.2.101

Abstract

Limb-Girdle Muscular Dystrophy 2B (LGMD2B) presents with proximal and/or distal muscle weakness and markedly high creatine kinase level. It is caused by the loss of dysferlin due to mutations in the DYSF gene. Due to its similar clinical features as inflammatory myopathy, it is often difficult to distinguish between the two. We present a case of a 48-year-old male who developed progressive proximal muscle weakness, papulosquamous lesions on the knuckles, elevated levels of muscle enzymes, and electromyogram abnormalities. Based on the clinical presentation, the initial impression was dermatomyositis, yet it was refractory to immunosuppressive therapy. Subsequently, dysferlin immunostaining and genetic analysis led to the final diagnosis of LGMD2B. This case shows that LGMD2B can present with extramuscular symptoms mimicking inflammatory myopathy in later stages of life. Dysferlin immunostaining and/or genetic analysis of the DYSF gene are essential for its diagnosis.

Keyword

Muscular dystrophies; Limb-girdle; Dermatomyositis

Figure

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  Figure 1 Changes in serum creatine kinase levels and daily doses of glucocorticoid during the follow-up period.

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  Figure 2 H&E stain (A) and immunohistochemistry (B∼D) of the muscle biopsy. (A) Myofibers show moderate size variation with degenerating cells with endomysial fibrofatty change (H&E, ×200). (B) Many degenerated myofibers show variation of size and positivity for CD56 (CD56 immunohistochemistry, ×100). Dystrophin (C) was robustly positive (Dystrophin 1 immunohistochemistry, ×200), yet dysferlin (D) was totally absent in the sarcolemmal membrane (Dysferlin immunohisto-chemistry, ×200).

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  Figure 3 Electron microscopy of the muscle. Myofibers show size variation with mild atrophic change. Lay-down of collagen are present within the endomysium (Uranyl acetate and lead citrate, ×6,000).

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  Figure 4 Sanger sequencing of the mutations in allele c.2548C>T (p.Gln850*) (nonsense mutation) (A) and c.3051G>T (p.Trp1017Cys) (missense mutation) (B) (arrows).

Reference

1. Dalakas MC. 2015; Inflammatory muscle diseases. N Engl J Med. 372:1734–47. DOI: 10.1056/NEJMra1402225. PMID: 25923553.

2. Bohan A, Peter JB. 1975; Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 292:344–7. DOI: 10.1056/NEJM197502132920706. PMID: 1090839.

3. Wicklund MP, Kissel JT. 2014; The limb-girdle muscular dystrophies. Neurol Clin. 32:729–49. DOI: 10.1016/j.ncl.2014.04.005. PMID: 25037088.

4. Nguyen K, Bassez G, Bernard R, Krahn M, Labelle V, Figarella-Branger D, et al. 2005; Dysferlin mutations in LGMD2B, Miyoshi myopathy, and atypical dysferlinopathies. Hum Mutat. 26:165. DOI: 10.1002/humu.9355. PMID: 16010686.

5. Choi JH, Park YE, Kim SI, Kim JI, Lee CH, Park KH, et al. 2009; Differential immunohistological features of inflammatory myopathies and dysferlinopathy. J Korean Med Sci. 24:1015–23. DOI: 10.3346/jkms.2009.24.6.1015. PMID: 19949654. PMCID: PMC2775846.

6. Park YE, Kim HS, Lee CH, Nam TS, Choi YC, Kim DS. 2012; Two common mutations (p.Gln832X and c.663+1G>C) account for about a third of the DYSF mutations in Korean patients with dysferlinopathy. Neuromuscul Disord. 22:505–10. DOI: 10.1016/j.nmd.2011.12.007. PMID: 22297152.

7. Bansal D, Miyake K, Vogel SS, Groh S, Chen CC, Williamson R, et al. 2003; Defective membrane repair in dysferlin-deficient muscular dystrophy. Nature. 423:168–72. DOI: 10.1038/nature01573. PMID: 12736685.

8. Petersen JA, Kuntzer T, Fischer D, von der Hagen M, Huebner A, Kana V, et al. 2015; Dysferlinopathy in Switzerland: clinical phenotypes and potential founder effects. BMC Neurol. 15:182. DOI: 10.1186/s12883-015-0449-3. PMID: 26444858. PMCID: PMC4596355.

9. Tarnopolsky MA, Hatcher E, Shupak R. 2016; Genetic myopathies initially diagnosed and treated as inflammatory myopathy. Can J Neurol Sci. 43:381–4. DOI: 10.1017/cjn.2015.386. PMID: 26911292.

10. Klinge L, Aboumousa A, Eagle M, Hudson J, Sarkozy A, Vita G, et al. 2010; New aspects on patients affected by dysferlin deficient muscular dystrophy. J Neurol Neurosurg Psychiatry. 81:946–53. DOI: 10.1136/jnnp.2009.178038. PMID: 19528035. PMCID: PMC2975994.

11. Biondi O, Villemeur M, Marchand A, Chretien F, Bourg N, Gherardi RK, et al. 2013; Dual effects of exercise in dysferlinopathy. Am J Pathol. 182:2298–309. DOI: 10.1016/j.ajpath.2013.02.045. PMID: 23624156.

12. Fanin M, Angelini C. 2016; Progress and challenges in diagnosis of dysferlinopathy. Muscle Nerve. 54:821–35. DOI: 10.1002/mus.25367. PMID: 27501525.

13. Vinit J, Samson M Jr, Gaultier JB, Laquerriere A, Ollagnon E, Petiot P, et al. 2010; Dysferlin deficiency treated like refractory polymyositis. Clin Rheumatol. 29:103–6. DOI: 10.1007/s10067-009-1273-1. PMID: 19730931.

14. Mammen AL. 2016; Statin-associated autoimmune myopathy. N Engl J Med. 374:664–9. DOI: 10.1056/NEJMra1515161. PMID: 26886523.

15. Park HJ, Hong JM, Suh GI, Shin HY, Kim SM, Sunwoo IN, et al. 2012; Heterogeneous characteristics of Korean patients with dysferlinopathy. J Korean Med Sci. 27:423–9. DOI: 10.3346/jkms.2012.27.4.423. PMID: 22468107. PMCID: PMC3314856.

16. Takahashi T, Aoki M, Suzuki N, Tateyama M, Yaginuma C, Sato H, et al. 2013; Clinical features and a mutation with late onset of limb girdle muscular dystrophy 2B. J Neurol Neurosurg Psychiatry. 84:433–40. DOI: 10.1136/jnnp-2011-301339. PMID: 23243261. PMCID: PMC3595148.