Skip to main content

Dysferlinopathy misdiagnosed with juvenile polymyositis in the pre-symptomatic stage of hyperCKemia: a case report and literature review



Dysferlinopathy encompasses a group of rare muscular dystrophies caused by recessive mutations in the DYSF gene. The phenotype ranges from asymptomatic elevated serum creatine kinase (hyperCKemia) to selective and progressive involvement of the proximal and/or distal muscles of the limbs. Bohan and Peter criteria are the most widely used for the diagnosis of polymyositis, but they have limitations and can misclassify muscular dystrophies with inflammation as polymyositis. Most dysferlinopathy patients have muscle biopsies with inflammation and thus are vulnerable to misdiagnosis with polymyositis and inappropriate treatment with steroids and immunosuppressors.

Case presentation

We describe a 14 years-old male patient who was referred for assessment of asymptomatic hyperCKemia (26,372 IU/L). An X-linked dystrophinopathy initially was ruled out by direct genetic testing. Juvenile polymyositis was considered based on muscle biopsy, creatine kinase levels, and electromyography changes. Corticosteroid treatment triggered proximal lower limb muscular weakness, and no full muscular strength recovery was observed after corticosteroid withdrawal. Based on these observations, a limb-girdle muscular dystrophy (LGMD) was suspected, and LGMDR2 was confirmed by whole exome sequencing.


We report a dysferlinopathy patient who was misdiagnosed with juvenile polymyositis and explore in a literature review how common such misdiagnoses are. With diagnosis based only on routine clinicopathological examinations, distinguishing an inflammatory myopathy from dysferlinopathy is quite difficult. We suggest that before establishing a diagnosis of “definite” or “probable” juvenile polymyositis, according to Bohan and Peter or current ACR/EULAR criteria, a muscular dystrophy must first be ruled out.

Peer Review reports


Dysferlinopathy encompasses a group of rare muscular dystrophies caused by recessive mutations in the DYSF gene. This gene encodes dysferlin, a transmembrane protein found in the sarcolemma, with an essential role in plasma membrane repair [1]. Mutations in DYSF are associated with a wide spectrum of phenotypes, ranging from asymptomatic elevated creatine kinase (CK) in the blood (hyperCKemia) to the selective and progressive involvement of the proximal and/or distal muscles of the limbs. The two major phenotypes are limb-girdle muscular dystrophy type 2B (LGMD2B), now called LGMDR2 according to the new nomenclature [2], presenting with proximal weakness in the lower limbs, and Miyoshi muscular dystrophy-1 (MMD1), a distal myopathy initially affecting the posterior compartment muscles of the leg. Other less frequent phenotypes include the more rapidly progressive distal myopathy with anterior tibial involvement, proximodistal weakness, and pseudometabolic presentation [3]. Although rare cases of congenital and late-onset presentation have been described, muscle weakness usually occurs in the teenage years or early adulthood (on average 15–27 years). The detection of dysferlin deficiency in muscle or blood and the identification of DYSF mutations are the main tools for diagnosing dysferlinopathy [4]. However, some clinical characteristics of dysferlinopathies such as proximal muscle weakness, elevated serum CK, and the prominent inflammatory findings on muscle biopsy may resemble idiopathic inflammatory myopathies (IIM).

Here we present a case of misdiagnosed dysferlinopathy with juvenile polymyositis (PM) and, based on a review of the literature, including the current evidences and classification criteria for IIM and the approach to the patient with hyperCKemia, we emphasize that PM is a rare disease and that before establishing a diagnosis of "definite" or "probable" juvenile PM, according to Bohan and Peter or ACR/EULAR criteria, muscular dystrophy with inflammatory features on muscle biopsy should be considered.

Case presentation

Here we present the case of a 14 years-old male patient in Mexico who was referred to our rheumatology department for assessment of an incidental finding of asymptomatic hyperCKemia (26,372 IU/L). There was no history of familial neuromuscular disorder or parental consanguinity or of exposure to myotoxic medications or substances. The patient engaged in 3 h daily of high-performance sports and had not experienced myalgia, cramps, or pigmenturia during or after physical activity. Initially, a neurologist considered that the hyperCKemia was related to exercise, but the patient’s CK serum levels persisted above 20,000 IU/L despite cessation of sports. Neuromuscular and systemic examination was normal, including an electromyography (EMG) and nerve conduction studies. No cardiac or respiratory complications were found. Myositis-specific (Mi2, TIF1g, MDA5, NXP2, SAE1, Jo1, SRP, PL7, PL12, EJ, OJ), myositis-associated (Ku, PM-Scl 75/100, Ro52), and antinuclear antibodies were negative. Thyroid-stimulating hormone level was normal.

Based on the patient’s sex and serum CK levels, an X-linked dystrophinopathy was suspected, but multiplex polymerase chain reaction analysis and multiplex ligation-dependent probe amplification analysis detected no DMD deletions. Six months later, the patient underwent muscle biopsy from the right quadriceps that showed necrosis along with endomysial and perivascular lymphocytic infiltrates, and no fibrosis or fatty infiltration was seen (Fig. 1). A new EMG and nerve conduction studies revealed a myopathic pattern. These findings were felt to be consistent with PM.

Fig. 1
figure 1

Right quadriceps muscle biopsy. Representative microscopic images of hematoxylin and eosin (HE) staining. A HE 40x, perivascular lymphocytic infiltrates are observed (arrow). B HE 30x, variation in fiber size (stars), degeneration, and necrosis is noted (arrows). These images were obtained using the following equipment: microscope BX53 and camera DP73 (Olympus, Tokyo, Japan). Scanner Hamamatsu, Nanozoomer S210-NDP. View 2 version 2.9.29, was used as acquisition software and the measurement resolution was 1200dpi

He was treated with intravenous methylprednisolone (IVMP) 1 g/day for 3 days and continued with prednisone 0.5 mg/kg/day and methotrexate 15 mg/weekly. Despite a decrease in CK serum levels from 28,457 to 21,671 IU/L, the patient began to experience proximal muscle weakness of both lower limbs, which worsened after a second monthly IVMP (500 mg/day for two days), with sparing of the upper limbs. Based on CK serum levels, the onset of proximal lower limb weakness after corticosteroid treatment, and the prominent inflammatory changes seen on muscle biopsy, a LGMD was suspected, and methotrexate and glucocorticoid treatment was suspended. After whole-exome sequencing (WES) (NGS; Illumina HiSeq 2500 sequencer), the diagnosis of LGMDR2 was confirmed based on a compound heterozygous variant of the DYSF gene. The first mutation was c.3851C > T, which causes a Gln →Ter amino acid change at position 1160 (p.Q1160X), leading to a stop codon in exon 32. The other mutation was a c.5979dup in exon 53, which causes a p.Glu1994ArgX3 frame shift. Sanger sequencing confirmed that the mother was a c.3851C > T carrier and that the father had the c.5979dup mutation (Fig. 2).

Fig. 2
figure 2

A Family pedigree showing the c.3851C > T and c.5979dup mutation carriers. The patient and his mother carried the c.3851C > T variant, while the patient and his father the c.5979dup variant. B Nucleotide chromatograms of the affected region. Red arrows indicate the variants

Discussion and conclusions

The juvenile forms of IIM (age at onset < 18 years) include juvenile PM, juvenile dermatomyositis, overlap myositis, and immune-mediated necrotizing myositis [5]. There is currently no widely accepted consensus regarding the classification of IIMs. The Bohan and Peter criteria are the most widely used for the definition of PM and dermatomyositis [6, 7]. According to these criteria, a diagnosis of definite PM requires all of the following: (1) proximal muscle weakness, (2) elevated serum CK, (3) EMG changes, and (4) muscle biopsy showing inflammation. All but the muscle biopsy findings are required for the diagnosis of probable PM. However, the Bohan and Peter criteria have some limitations because they do not clearly specify how to exclude other forms of myopathy, leading to the potential for misclassification. In a recent study of 255 patients classified as having definite or probable IIM by the current EULAR/ACR criteria [8], 124 were classified as PM, but only 37 (14.5%) were classified as PM according to expert opinion [9]. Furthermore, a detailed review of these 37 cases led to only 9 (24.3%) patients remaining classified as PM, corresponding only to 3.5% (9/255) of the original cohort [10].

Over time, PM has been questioned as a distinct entity, and many of these patients may be better described as having an alternative diagnosis [11,12,13,14,15]. Dermatomyositis is well recognized in children, but the existence of juvenile PM has been highly debated [16, 17]. In fact, it took almost 10 years to recruit enough patients to establish the current EULAR/ACR criteria for adult and juvenile IIM, and even then, the number of children with PM was insufficient for adequate study. For this reason, pediatric rheumatology experts on the International Myositis Classification Criteria Project have recommended extrapolating the adult subclassification of IIM criteria for juvenile PM [8].

Inherited myopathies such as calpainopathy, dysferlinopathy, facioscapulohumeral muscular dystrophy, and dystrophinopathy may be associated with inflammation on muscle biopsy. They also frequently present with proximal muscle weakness, elevated CK, and EMG with a myopathic pattern. Therefore, the differential diagnosis of PM from muscular dystrophies, based upon histologic and clinical findings, may be challenging [18, 19]. In a retrospective clinicopathological analysis from Australia, for example, of 13 cases with an initial diagnosis of juvenile PM, 12 (92.3%) were found to be muscular dystrophy, suggesting that juvenile PM is extremely uncommon, if it exists at all [17].

In the case of dysferlinopathy, most patients have muscle biopsies with an increased inflammatory response [20, 21], even those who are clinically less affected, suggesting that this manifestation is a relatively early feature [22]. Therefore, dysferlinopathy patients are most vulnerable to misdiagnosis with PM. Indeed, in an international multicenter study that included 193 patients, 16% with dysferlinopathy were misdiagnosed with PM [23], and another 10 of 40 patients (25%) were likewise misdiagnosed in a study in two French neuromuscular centers [3]. A systematic review of the literature was performed in PubMed database to identify all relevant reports of dysferlinopathy misdiagnosed as polymyositis. The key search terms included “dysferlinopathy”, “polymyositis”, “inflammatory myopathy”, “case report” & “misdiagnosis”. All case reports and case series of patients with dysferlinopathy published between 1999 and 2021 were eligible for inclusion. There were no language restrictions in the searching. Based on these criteria, a total of 20 studies meet the selection criteria giving a total of 32 dysferlinopathy cases [16, 20, 22, 24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40], reported as case reports or small case series, that were misdiagnosed with PM (Table 1).

Table 1 Review of reported cases of dysferlinopathy misdiagnosed with polymyositis

Of these, 55% were female, the median age at onset of symptoms was 21.5 years (range, 14–50 years), and onset in 33% of cases was before age 18 years. The median time elapsed for the diagnosis was 5 years (range, 0–28 years), and the LGMDR2 phenotype was reported in 57% (16/28). Thus, dysferlinopathy can be diagnostically challenging because of its considerable genetic and phenotypic heterogeneity and clinical and histological characteristics that overlap with IIM.

Establishing an accurate differential diagnosis is imperative not only to guide treatment, prognosis, and genetic counseling but also to prevent unnecessary and potentially harmful treatment. One case series of 20 patients with dysferlinopathy who were initially misdiagnosed as having inflammatory myopathy showed that muscular strength may worsen after corticosteroid treatment and might not be regained after cessation of corticosteroids [14]. Likewise, in a randomized controlled trial with deflazacort, dysferlinopathy patients did not improve during the treatment period, and there was a trend to worsening in muscle strength [41]. Here, we report a case of a 14 years-old male patient with dysferlinopathy and pre-symptomatic hyperCKemia, in whom muscular weakness was triggered by corticosteroid treatment for misdiagnosed juvenile PM. Furthermore, he did not experience full muscular strength recovery after stopping treatment.

Although based on direct peer guidelines for asymptomatic hyperCKemia it was more likely to be dystrophinopathy [42], this was discarded by direct genetic testing. Next-generation sequencing techniques provide a potential way to overcome diagnostic delays. WES yields a higher diagnostic rate than sequential genetic testing for undiagnosed patients with limb-girdle weakness [43]. In our patient, two previously described DYSF mutations [3, 44], were detected by WES. Both variants cause a truncated version of the protein. Although immunodetection on muscle biopsies has shown that dysferlinopathy represent the second largest proportion of rare muscular dystrophies (18.45%) after dystrophinopathies (52.3%) in Mexico [45], the characterization of DYSF mutations is scarce [46]. In fact, the c.3851C > T mutation has been described only in one Mexican MMD1 patient, and although the c.5979dup mutation has been characterized as frequent [47], this is the first report in a Mexican patient. Furthermore, neither of these mutations was found in 2217 exomes from Mexican volunteers from a previous study [48], although we found seven variants predicted to be pathogenic and described in the Mexican population for the first time (Table 2). Thus, personalized and precision medicine is critical in highly heterogeneous diseases such as IIM and LGMD. In line with this, some therapeutic approaches should be considered, such as the use of antisense-induced exon skipping, which has shown promising results for DYSF exon 32 skipping. The deletion of this exon produces a mild phenotype, making this exon suitable for exon skipping [49].

Table 2 Most frequent variants with clinical implications identified from 2217 exomes from Mexican Amerindian and Mestizo individuals

In conclusion, distinguishing an inflammatory myopathy from dysferlinopathy is quite difficult if diagnosis is based only on routine clinicopathological examination. We suggest that before establishing a diagnosis of “definite” or “probable” juvenile PM, according to Bohan and Peter or ACR/EULAR criteria, muscular dystrophy with inflammatory characteristics on muscle biopsy must first be ruled out. For an accurate diagnosis, immunohistochemistry or Western blot analysis should be applied to identify reduction or loss of protein, and/or genetic analysis by WES applied to identify mutations and rule out other muscular dystrophies. These steps, along with a strategy for approaching the history and examination of patients with hyperCKemia may help the clinician to identify the etiology of hyperCKemia and prevent more misdiagnoses and inappropriate treatment with steroids and immunosuppressors in patients with dysferlinopathy.

Availability of data and materials

The variant data for this study have been deposited in the European Variation Archive (EVA) at EMBL-EBI under accession number PRJEB53236. ( The data concerning the DYSF variants in 2217 exomes from Mexican volunteers were obtained from a previous study [48].



Limb-girdle muscular dystrophy


Creatine kinase


Miyoshi muscular dystrophy-1






Intravenous methylprednisolone


Whole-exome sequencing


Idiopathic inflammatory myopathies


  1. Bansal D, Miyake K, Vogel SS, Groh S, Chen CC, Williamson R, et al. Defective membrane repair in Dysferlin-deficient muscular dystrophy. Nature. 2003;423(6936):168–72.

    Article  CAS  PubMed  Google Scholar 

  2. Straub V, Murphy A, Udd B, LGMD Workshop Study Group. 229th ENMC international workshop: limb girdle muscular dystrophies—nomenclature and reformed classification Naarden, the Netherlands. Neuromuscul Disord. 2018;28(8):702–10.

    Article  PubMed  Google Scholar 

  3. Nguyen K, Bassez G, Krahn M, Bernard R, Laforêt P, et al. Phenotypic study in 40 patients with Dysferlin gene mutations: high frequencyof atypical phenotypes. Arch Neurol. 2007;64(8):1176–82.

    Article  PubMed  Google Scholar 

  4. Fanin M, Angelini C. Progress and challenges in diagnosis of dysferlinopathy. Muscle Nerve. 2016;54(5):821–35.

    Article  CAS  PubMed  Google Scholar 

  5. Huber AM. Juvenile idiopathic inflammatory myopathies. Pediatr Clin North Am. 2018;65(4):739–56.

    Article  PubMed  Google Scholar 

  6. Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 1975;292(7):344–7.

    Article  CAS  PubMed  Google Scholar 

  7. Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). N Engl J Med. 1975;292(7):403–7.

    Article  CAS  PubMed  Google Scholar 

  8. Lundberg IE, Tjärnlund A, Bottai M, Werth VP, Pilkington C, Visser M, et al. 2017 European League against Rheumatism/American college of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis. 2017;76(12):1955–64.

    Article  PubMed  Google Scholar 

  9. Parker MJS, Oldroyd A, Roberts ME, Lilleker JB, Betteridge ZE, McHugh NJ, et al. The performance of the European League against Rheumatism/American college of Rheumatology idiopathic inflammatory myopathies classification criteria in an expert-defined 10 year incident cohort. Rheumatology. 2019;58(3):468–75 (Oxford).

    Article  PubMed  Google Scholar 

  10. Loarce-Martos J, Lilleker JB, Parker M, McHugh N, Chinoy H. Polymyositis: is there anything left. A retrospective diagnostic review from a tertiary myositis centre. Rheumatology. 2021;60(7):3398–403 (Oxford).

    Article  CAS  PubMed  Google Scholar 

  11. van der Meulen MF, Bronner IM, Hoogendijk JE, Burger H, van Venrooij WJ, Voskuyl AE, Dinant HJ, et al. Polymyositis: an overdiagnosed entity. Neurology. 2003;61(3):316–21.

    Article  PubMed  Google Scholar 

  12. Amato AA, Griggs RC. Unicorns, dragons, polymyositis, and other mythological beasts. Neurology. 2003;61(3):288–9.

    Article  PubMed  Google Scholar 

  13. Mariampillai K, Granger B, Amelin D, Guiguet M, Hachulla E, Maurier F, et al. Development of a new classification system for idiopathic inflammatory myopathies based on clinical manifestations and myositis-specific autoantibodies. JAMA Neurol. 2018;75(12):1528–37.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Hoffman EP, Rao D, Pachman LM. Clarifying the boundaries between the inflammatory and dystrophic myopathies: insights from molecular diagnostics and microarrays. Rheum Dis Clin North Am. 2002;28(4):743–57.

    Article  PubMed  Google Scholar 

  15. Leclair V, Notarnicola A, Vencovsky J, Lundberg IE. Polymyositis: does it really exist as a distinct clinical subset? Curr Opin Rheumatol. 2021;33(6):537–43.

    Article  CAS  PubMed  Google Scholar 

  16. Benveniste O, Romero NB. Myositis or dystrophy. Traps and pitfalls. Presse Med. 2011;40(4 Pt 2):e249–55.

    Article  PubMed  Google Scholar 

  17. D’Arcy CE, Ryan MM, McLean CA. Juvenile polymyositis or paediatric muscular dystrophy: a detailed re-analysis of 13 cases. Histopathology. 2009;55(4):452–62.

    Article  PubMed  Google Scholar 

  18. Michelle EH, Mammen AL. Myositis mimics. Curr Rheumatol Rep. 2015;17(10):63.

    Article  PubMed  CAS  Google Scholar 

  19. Mammen AL. Which nonautoimmune myopathies are most frequently misdiagnosed as myositis? Curr Opin Rheumatol. 2017;29(6):618–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Gallardo E, Rojas-García R, de Luna N, Pou A, Brown RH Jr, Illa I. Inflammation in Dysferlin myopathy: immunohistochemical characterization of 13 patients. Neurology. 2001;57(11):2136–8.

    Article  CAS  PubMed  Google Scholar 

  21. Fanin M, Angelini C. Muscle pathology in Dysferlin deficiency. Neuropathol Appl Neurobiol. 2002;28(6):461–70.

    Article  CAS  PubMed  Google Scholar 

  22. Rowin J, Meriggioli MN, Cochran EJ, Sanders DB. Prominent inflammatory changes on muscle biopsy in patients with Miyoshi myopathy. Neuromuscul Disord. 1999;9(6–7):417–20.

    Article  CAS  PubMed  Google Scholar 

  23. Harris E, Bladen CL, Mayhew A, James M, Bettinson K, et al. The clinical outcome study for dysferlinopathy: an international multicenter study. Neurol Genet. 2016;2(4):e89.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Cho HJ, Sung DH, Kim EJ, Yoon CH, Ki CS, Kim JW. Clinical and genetic analysis of Korean patients with Miyoshi myopathy: identification of three novel mutations in the DYSF gene. J Korean Med Sci. 2006;21:724–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Selva-O’Callaghan A, Labrador-Horrillo M, Gallardo E, Herruzo A, Grau-Junyent JM, Vilardell-Tarres M. Muscle inflammation, autoimmune Addison’s disease and sarcoidosis in a patient with Dysferlin deficiency. Neuromuscul Disord. 2006;16:208–9.

    Article  PubMed  Google Scholar 

  26. Pimentel LH, Alcântara RN, Fontenele SM, Costa CM, Gondim FA. Limb-girdle muscular dystrophy type 2B mimicking polymyositis. Arq Neuropsiquiatr. 2008;66:80–2.

    Article  PubMed  Google Scholar 

  27. Vinit J, Samson M Jr, Gaultier JB, Laquerriere A, Ollagnon E, Petiot P, et al. Dysferlin deficiency treated like refractory polymyositis. Clin Rheumatol. 2010;29:103–6.

    Article  PubMed  Google Scholar 

  28. Vernengo L, Oliveira J, Krahn M, Vieira E, Santos R, Carrasco L, Negrão L, et al. Novel ancestral Dysferlin splicing mutation which migrated from the Iberian peninsula to South America. Neuromuscul Disord. 2011;21:328–37.

    Article  PubMed  Google Scholar 

  29. Angelini C, Grisold W, Nigro V. Diagnosis by protein analysis of dysferlinopathy in two patients mistaken as polymyositis. Acta Myol. 2011;30:185–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Park YE, Kim HS, Lee CH, Nam TS, Choi YC, Kim DS. 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. 2012;22:505–10.

    Article  PubMed  Google Scholar 

  31. Park HJ, Hong JM, Suh GI, Shin HY, Kim SM, Sunwoo IN, et al. Heterogeneous characteristics of Korean patients with dysferlinopathy. J Korean Med Sci. 2012;27:423–9.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Li F, Yin G, Xie Q, Shi G. Late-onset dysferlinopathy presented as “liver enzyme” abnormalities: a technical note. J Clin Rheumatol. 2014;20:275–7.

    Article  PubMed  Google Scholar 

  33. Loureiro Amigo J, Gallardo E, Gallano P, Grau-Junyent JM. Disferlinopatía, una causa de falsa polimiositis refractaria [Dysferlinopathy masquerading as a refractory polymyositis]. Med Clin (Barc). 2015;145:414–5.

    Article  Google Scholar 

  34. Griger Z, Nagy-Vincze M, Bodoki L, Gherardi RK, Dankó K, Hortobágyi T. Late onset dysferlinopathy mimicking treatment resistant polymyositis. Joint Bone Spine. 2016;83:355–6.

    Article  PubMed  Google Scholar 

  35. Tarnopolsky MA, Hatcher E, Shupak R. Genetic myopathies initially diagnosed and treated as inflammatory myopathy. Can J Neurol Sci. 2016;43:381–4.

    Article  PubMed  Google Scholar 

  36. Wang M, Guo Y, Fu Y, Jia R, Chen G. Atypical Miyoshi distal myopathy: a case report. Exp Ther Med. 2016;12:3068–72.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Scalco RS, Lorenzoni PJ, Lynch DS, Martins WA, Jungbluth H, Quinlivan R, et al. Polymyositis without beneficial response to steroid therapy: should Miyoshi myopathy be a differential diagnosis? Am J Case Rep. 2017;18:17–21.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Ceccon G, Lehmann HC, Neuen-Jacob E, Meng G, Fink GR, Wunderlich G. Therapierefraktäre Polymyositis“—stimmt die diagnose? “Therapy-resistant polymyositis”—is the diagnosis correct? Z Rheumatol. 2017;76:640–3 (German).

    Article  CAS  PubMed  Google Scholar 

  39. Xu C, Chen J, Zhang Y, Li J. Limb-girdle muscular dystrophy type 2B misdiagnosed as polymyositis at the early stage: case report and literature review. Medicine. 2018;97:e10539 (Baltimore).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Tang J, Song X, Ji G, Wu H, Sun S, Lu S, et al. A novel mutation in the DYSF gene in a patient with a presumed inflammatory myopathy. Neuropathology. 2018. 

  41. Walter MC, Reilich P, Thiele S, Schessl J, Schreiber H, Reiners K, et al. Treatment of dysferlinopathy with deflazacort: a double-blind, placebo-controlled clinical trial. Orphanet J Rare Dis. 2013;8:26.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Venance SL. Approach to the patient with HyperCKemia. Continuum (Minneap Minn). 2016;22(6):1803–14.

    Google Scholar 

  43. Harris E, Topf A, Barresi R, Hudson J, Powell H, Tellez J, et al. Exome sequences versus sequential gene testing in the UK highly specialised service for limb girdle muscular dystrophy. Orphanet J Rare Dis. 2017;12(1):151.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Aoki M, Liu J, Richard I, Bashir R, Britton S, et al. Genomic organization of the Dysferlin gene and novel mutations in Miyoshi myopathy. Neurology. 2001;57:271–8.

    Article  CAS  PubMed  Google Scholar 

  45. Gómez-Díaz B, Rosas-Vargas H, Roque-Ramírez B, Meza-Espinoza P, Ruano-Calderón LA, Fernández-Valverde F, et al. Immunodetection analysis of muscular dystrophies in Mexico. Muscle Nerve. 2012;45(3):338–45.

    Article  PubMed  Google Scholar 

  46. Escobar-Cedillo RE, López-Hernández L, Miranda-Duarte A, Curiel-Leal MD, Suarez-Ocón A, Sánchez-Chapul L, Berenice Luna-Angulo A, et al. Genetic analysis of muscular dystrophies: our experience in Mexico. Folia Neuropathol. 2021;59(3):276–83.

    Article  PubMed  Google Scholar 

  47. Nguyen K, Bassez G, Bernard R, Krahn M, Labelle V, Figarella-Branger D, et al. Dysferlin mutations in LGMD2B, Miyoshi myopathy, and atypical dysferlinopathies. Hum Mutat. 2005;26:165.

    Article  PubMed  Google Scholar 

  48. Flannick J, Mercader JM, Fuchsberger C, Udler MS, Mahajan A, Wessel J, et al. Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls. Nature. 2019;570(7759):71–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Wein N, Avril A, Bartoli M, Beley C, Chaouch S, Laforêt P, et al. Efficient bypass of mutations in Dysferlin deficient patient cells by antisense-induced exon skipping. Hum Mutat. 2010;31(2):136–42.

    Article  CAS  PubMed  Google Scholar 

Download references


We thank the patient and parents for participating in this report.


Not applicable.

Author information

Authors and Affiliations



CCC planned and performed the genetic studies; VB carried out the literature review and the patient´s medical record; FBO and HGO performed the analysis of 2217 exomes from Mexican volunteer individuals; MIFM performed the electromyography studies; GSR performed the pathological studies; CCGS performed the patient´s functional clinical evaluation; LO and VB conducted and designed the research. EMSM, FBO, MIFM, AGSR, CCGS and HGO helped draft the manuscript. CCC, LO, and VB were the major contributors in the writing and critical review of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Vicente Baca.

Ethics declarations

Ethics approval and consent to participate

Ethical approval was given by the Comité Local de Investigación en Salud del Hospital de Pediatría, Centro Médico Nacional Siglo XXI, 2021-09-13 3603. Written informed consent was obtained from the patient and both parents.

Consent for publication

Written informed consent was obtained from the patient´s parents and the patient for publication of this case report.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Contreras-Cubas, C., Barajas-Olmos, F., Frayre-Martínez, M.I. et al. Dysferlinopathy misdiagnosed with juvenile polymyositis in the pre-symptomatic stage of hyperCKemia: a case report and literature review. BMC Med Genomics 15, 139 (2022).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI:


  • Dysferlinopathy
  • Polymyositis
  • Limb-girdle muscular dystrophy
  • Case report
  • Whole exome sequencing