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

Abstract

Background 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. Conclusion 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.

Molecular Diagnosis of Limb-Girdle Muscular Dystrophy Using Next-Generation Sequencing Panels

“…Recent papers reported that patients with asymptomatic hy-perCKemia may have muscular dystrophy [Alcahut-Rodríguez et al, 2020;Lee et al, 2021]. It has been emphasized that patients with pathogenic changes in LGMD-related genes may present with asymptomatic CK elevation [Lee et al, 2021;Alcahut-Rodríguez et al, 2020;Contreras-Cubas et al, 2022]. There is a growing body of literature that recognizes that genetic analysis methods can detect patients while they are asymptomatic [Alcahut-Rodríguez et al, 2020;Lee et al, 2021].…”

Miyoshi Muscular Dystrophy Type 1 with Mutated DYSF Gene Misdiagnosed as Becker Muscular Dystrophy: A Case Report and Literature Review

“…However, the pathological findings on routine histopathological and immunohistochemical stains and heterogeneity of clinical manifestations make it difficult to diagnose dysferlinopathy [19]. Several patients with dysferlinopathy have been previously misdiagnosed with inflammatory myopathy [19,20] and juvenile polymyositis [21,22]. In the case of dysferlinopathy, most patients received muscle biopsies for increased inflammatory responses [23,24], even those who were less affected clinically, suggesting that this sign is a relatively early feature [25].…”

В6.А-DYSFPRMD/GENEJ Mice as a Genetic Model of Dysferlinopathy

“…[1]. Дисферлинопатия включает в себя пресимптоматический этап бессимптомного повышения уровня креатинкиназы (КК) в крови и манифестный этап, характеризующийся прогрессирующим поражением проксимальных и/ или дистальных мышц конечностей [2]. Различают пять основных фенотипов дисферлинопатии: дистальная миопатия Миоши (OMIM # 254130), поясно-конечностная мышечная дистрофия R2 (LGMD R2, OMIM # 253601); дистальная миопатия переднего ложа голени (дистальная, с началом в передней большеберцовой мышце (DMAT, OMIM # 606768); проксимально-дистальная форма (переходная форма) и врожденный фенотип [3].…”