Dysferlin-deficient limb-girdle muscular dystrophy type 2B (LGMD2B), distal Miyoshi myopathy (MM) and other less frequent phenotypes constitute a group of recessive disorders known as dysferlinopathies. MM with autosomal recessive inheritance and localization to chromosome 2p is caused by autosomal recessive mutations in the human dysferlin gene (DYSF) (1,2). In cases of MM, the involvement of the gastrocnemius and soleus muscles, which causes a difficulty in standing on one's tiptoes, is characteristic. Clinical signs usually present for individuals between the late teens and prior to the age of 30 years. According to its clinical and histopathological manifestations, MM has been categorized as a distal myopathy with typical symptoms of muscular dystrophy (3,4). Distal MM is also known as Miyoshi-type distal muscular dystrophy, and was first reported in 1986 by Miyoshi et al (5). Subsequently, an increasing number of cases of MM have been reported, particularly in Japan, Brazil, Finland and South Korea (6–8). In China, there has only been one report of MM in a family in 2004 (9). According to conservative estimates, the incidence of MM is ~l/440,000 in Japan (10). Among the Jewish population in Libya, 10% have been found to be carriers of the DYSF gene mutation (1,624 delG), and the incidence of LGMD2B in adults from this population has reached l/1,300 (11,12). However, the corresponding statistics in China remain unknown.

The present case report describes an atypical MM patient, who was initially misdiagnosed with inflammatory myopathy and finally was diagnosed with MM according to pathology, immunohistochemistry and electromyography.

Distal myopathy is a disease characterized by distal limb muscle weakness. According to the onset age, affected muscles and genetic factors, distal myopathy is divided into several subtypes (13).

Congenital defect of dysferlin expression on muscle cell membrane has been suggested to be associated with MM (4), which features a marked increase in blood CK levels, compared with that in other subtypes of distal myopathy. The significant dysferlin protein deficiency of the present case, indicated by immunohistochemical staining of the muscle, suggested distal myopathy. The differential diagnosis criteria of common types of distal myopathy are shown in Table I.

The patient of the present study reported no family history of Miyoshi myopathy. One clinical manifestation in the present case was the inability to stand on tiptoe on the left foot. Progressively, the CK levels in the patient's peripheral blood increased markedly. According to the classification of distal myopathy presented in Table I, these clinical manifestations are suggestive of a diagnosis of distal MM.

MM is an autosomal recessive disease caused by a DYSF gene mutation, located on chromosome 2p13 (1). Dysferlin protein is encoded by DYSF. The DYSF gene mutation leads to a deficiency of dysferlin proteins, which results in dysferlinopathy. The majority of MM patients present with the initial symptoms between 15 and 30 years of age; but the patients have a broader range of ages of onset (12–36 years) (14). In distal MM, the initial symptoms are in the posterior compartment of the distal lower extremity, which causes an inability to walk on tiptoes or up stairs (15). Pain and discomfort in the calves may also occur (16). The gastrocnemius muscles become atrophic and the stretch reflexes of the ankle muscle are lost (17). The tendency for early involvement of the gastrocnemius muscles has been considered the clinical hallmark of distal MM, which distinguishes it from other distal dystrophies (13). However, muscles of the anterior compartment of the distal lower extremities eventually weaken as well (18). The involvement of upper extremities is unusual in the early stages of the disease (16). With the progression of the disease, patients may develop proximal leg and arm weakness to various degrees (16). The hamstring muscle group (knee flexors) may become weaker than the quadriceps muscles (knee extensors), which has implications for the choice of biopsy site (19). Disease progression varies from patient to patient, with some remaining moderately stable with distal weakness, and others presenting a more aggressive pattern, involving both proximal and distal muscles (5). A characteristic laboratory finding of the disease is a marked increase in serum CK levels, up to 20–150-fold above normal (20). In certain cases, an extremely high CK level may be detected during routine blood tests before any clinical weakness or atrophy is present (21,22).

Although dysferlinopathy is caused by a single DYSF gene, it is well-known that dysferlinopathy has various clinical presentations, such as distal MM, LGMD2B and distal anterior compartment myopathy (Table II). The early involved muscles determine the clinical phenotype of dysferlinopathy. In the present case, the gastrocnemius was the initially involved muscle, which matched the symptoms of MM. In addition, the immunohistochemical analyses, using an anti-dysferlin monoclonal antibody, showed a deficiency or marked reduction in dysferlin on the sarcolemma.

In the present case, a 37-year old male patient presented with the inability to stand on his left foot for 1 month prior to admission to the hospital. Initially, the patient was considered to have inflammatory myopathy, on the basis of an EMG examination. Following treatment with hormone therapy, the CK level temporarily dropped to 1,493.8 U/l, but subsequently increased to 2,698.2 U/l following the reduction in hormone administration, with no obvious improvement of the symptoms. Subsequently, pathological muscle examinations were conducted. The results of pathological muscle examination, such as the muscle fiber size, and necrotic and regenerating muscle fibers, as well as total absence of dysferlin on the sarcolemma in immunohistochemical staining of muscle, played an important role in diagnosing the patient with dysferlinopathy.

In atypical MM, the following characteristics of the present patient could lead to misdiagnosis: i) The patient was 37 years old, while MM is predominantly observed at a younger age (15–20 years); ii) the onset time was short; 1 month in the present case, in the report by Park et al (14) about typical MM, the course was 2–30 years; iii) the muscle involved was unilateral in the present patient, but in the reports by Wang et al (16), Zhang et al (17) and Gayathri et al (23) typical MM was bilateral; and iv) the present case was sporadic; however, typically MM is a rare autosomal recessive inherited myopathy and sporadic cases are uncommon.

Due to certain pathological features that are observed in cases of MM, such as muscle weakness, elevation of CK levels and mononuclear cell infiltration, it is not rare for the disease to be misdiagnosed as inflammatory myopathy. A previous study found that certain patients with MM also present with gastrocnemius muscle myalgia, swelling and even false hypertrophy at the early stage of the disease (12). The pathogenesis of these symptoms is not clear and may be associated with transient inflammatory reaction. The early symptoms of MM are not typical and are readily misdiagnosed; therefore, the pathological muscle examination should be undertaken as soon as possible. In particular, immunohistochemical staining including anti-dysferlin monoclonal antibodies may be useful for the identification of possible dysferlin deficiency.