The aim of this study was to clinically and genetically characterize male patients who have normal or mildly elevated creatinine kinase (CK) levels with a genetically confirmed dystrophinopathy, but no clinical symptoms of muscle weakness.

Mild form of dystrophinopathies present with muscle cramps with myoglobinuria  or asymptomatic increase in serum concentration of CK. Patients with dystrophinopathies irrespective of their severity tend to have markedly elevated CK levels indicating muscle damage.

This study was conducted as a retrospective chart review from a single tertial referral hospital’s pediatric neuromuscular clinic. Male children presenting at less than 18 years of age, who had dystrophinopathy confirmed by genetic testing and had normal CK levels and no evidence of muscle weakness were enrolled. The clinical and genetic profile were analyzed.

A total of 6 cases were identified. Four had normal CK and 2 cases had mild CK elevation (<2x ULN). All had identified mutations in the dystrophin gene. The patients age ranged from 20 months to 15 years at last follow up. All patients were ambulatory, 1/6 patients had mild global delay (walking after 15 months). No patients had evidence of muscle weakness. 5/6 had positive family history.

Most commonly, mutations in the DMD gene are associated with marked elevation in serum CK since birth (10–100 times). Serum CK levels are a valuable screening test for dystrophin related conditions in symptomatic patients. However, we show that a number of patients with DMD mutations can have a normal or near normal CK. While these patients do not have muscle symptoms presenting in childhood, they remain at risk for adult onset weakness, cardiomyopathy and exertional rhabdomyolysis. These findings are also relevant to proposed newborn screening for DMD which uses serum CK as the screening test.