Heterogeneous characteristics of Korean patients with dysferlinopathy

Abstract

Dysferlinopathy is caused by mutations in the DYSF gene. To characterize the clinical spectrum, we investigated the characteristics of 31 Korean dysferlinopathy patients confirmed by immunohistochemistry. The mean age of symptom onset was 22.23 ± 7.34 yr. The serum creatine kinase (CK) was highly increased (4- to 101-fold above normal). The pathological findings of muscle specimens showed nonspecific dystrophic features and frequent inflammatory cell infiltration. Muscle imaging studies showed fatty atrophic changes dominantly in the posterolateral muscles of the lower limb. The patients with dysferlinopathy were classified by initial muscle weakness: fifteen patients with Miyoshi myopathy phenotype (MM), thirteen patients with limb girdle muscular dystrophy 2B phenotype (LGMD2B), two patients with proximodistal phenotype, and one asymptomatic patient. There were no differences between LGMD2B and MM groups in terms of onset age, serum CK levels and pathological findings. Dysferlinopathy patients usually have young adult onset and high serum CK levels. However, heterogeneity of clinical presentations and pathologic findings upon routine staining makes it difficult to diagnose dysferlinopathy. These limitations make immunohistochemistry currently the most important method for the diagnosis of dysferlinopathy.

Keywords: Dysferlin; Limb-Girdle Muscular Dystrophy Type 2B; Miyoshi Myopathy; mmunohistochemistry.

Fig. 1

Pathological features of dysferlinopathy. (A) Dysferlin in a normal muscle specimen by immunohistochemistry (× 200). (B) Loss of dysferlin in a nearly total muscle specimen by immunohistochemistry (× 200). (C) Prominent inflammatory cell infiltration and increased endomysial fibrosis on H&E stain (× 200). (D) A few necrotic (^*) and regenerating muscle fibers (▪) on modified Gomori trichrome stain (× 200).

Fig. 2

Radiological features of dysferlinopathy. Muscle CT scans revealed that muscles of the upper limb (A) are relatively spared and lateral posterior compartments of thigh (B) and calf (C) muscles had dominantly fatty atrophic changes. Transverse T1 weighted images through thigh (D) and calf (E) muscles revealed that lateral posterior muscles had dominantly fatty atrophic changes.