Becker Muscular Dystrophy in a 2-Year-Old Boy caused by a Novel Missense Mutation p.Arg145Pro in the Dystrophin Gene

Background: X-linked dystrophinopathy, resulting from mutations in the dystrophin gene, is the most common cause of inherited myopathy in males. On the molecular level, Becker muscular dystrophy (BMD) is caused by deletions, point mutations, or duplications in the dystrophin gene. Although the genetic defect and the impaired formation of dystrophin are already present from birth, males with Duchenne muscular dystrophy (DMD) or the milder BMD are born with normal muscle function and develop progressive muscle weakness as they age. In BMD, the pattern of symptom development resembles that of DMD, but with a later, and much slower rate of progression.

Case: We report the case of a 2.5-year-old boy showing an elevation of the Creatine kinase (CK) up to 25,000 U/L associated with an infection and hepatosplenomegaly. The boy revealed age-appropriate physical development; in particular, an unremarkable muscle status as well as a timely achievement of the motoric milestones. After excluding infection as a cause of the CK-elevation, a genetic analysis was performed in the family for suspected dystrophinopathy. DNA sequence analysis did neither detect a duplication nor a deletion, but an unknown de novo missense mutation (exon 6: c.434G > C; p.Arg145Pro) in the dystrophin gene of the index patient and as heterozygous mutation in his mother. The maternal grandparents had normal dystrophin gene analysis.

A muscle biopsy in the index patient showed partial but insufficient function of the protein dystrophin and established the diagnosis of BMD.

Conclusion: The progression of BMD is highly variable. Nevertheless, 90% of all patients develop a cardiomyopathy (CM), which is fatal in 50% of all cases. Therefore, it is important to consider dystrophinopathy in the differential diagnosis of persistent hyperCKaemia even in asymptomatic patients. In those, clinical follow-up, genetic analysis, and a muscle biopsy, should be performed to closely monitor for the development of CM. Discovering CM at an early stage should help initiate an early treatment, reducing the progress of cardiac insufficiency.

Keywords: Becker muscular dystrophy, HyperCKaemia, dystrophinopathy.