Case report

A 24-year-old man had experienced hip-girdle weakness since the age of 15 years and exercise-induced muscle cramps with ‘toe-walking’ since aged 12 years. He was thought to have Marfan's syndrome but had no known family history of muscle disease. His marfanoid features prompted a transthoracic echocardiogram at 18 years, showing a normal aortic root and cardiac size/function without mitral valve prolapse.

On examination at the age of 24, he was tall (6 feet, 7 inches; 201 cm) with an asthenic habitus, disproportionate arm length to height (1.06), high-arched palate, arachnodactyly, marked pectus excavatum and pes planus, but no other features of Marfan's syndrome. Neuromuscular examination showed hypertrophy of calf muscles and shortening of the Achilles’ tendons as well as selective atrophy of the sternal heads of sternocleidomastoid muscles, proximal arms and quadriceps muscles. There was no scapular winging. The limb-girdle pattern of weakness was of moderate severity (Medical Research Council (MRC) grade 3) in the hip extensors and adductors, and knee flexors and mild weakness (MRC grade 4) in neck flexors, hip flexors and abductors, as well as knee extensors. The strength in other muscle groups and the remaining neurological examination, including tendon reflexes, was normal.

He remained fully ambulant and functional at the age of 31 years, albeit with a moderately waddling gait.

His 12-lead ECG at age 24 was abnormal, with a right-bundle branch pattern and a prominent R wave in chest lead V2. Echocardiography showed borderline dilatation and reduced function of both ventricles. The ECG and echocardiogram were unchanged when re-examined 7 years later.

Laboratory tests showed a serum creatine kinase of 1640 IU/L (>10 times the upper limit of normal). Biopsy of the quadriceps femoris showed an increase in endomysial connective tissue, infiltration of adipose tissue and focal necrotic fibres. Immunohistochemistry showed normal spectrin and caveolin staining but decreased intensity (∼50%) in the …