Myalgic Beckers Muscular Dystrophy Due to an Exon 15 Point Mutation: Case Series and Literature Review

Background: Dystrophinopathies result from mutations to the DMD gene. Presentation varies from asymptomatic elevations in creatine kinase levels to early loss of ambulation and significant impairment as seen in Duchenne's muscular dystrophy. We report 5 boys in 3 families with heterogenous phenotypes due to a point mutation in the DMD gene: a hemizygous tyrosine-to-cysteine change in exon 15 (c.1724T>C) resulting in an amino acid substitution of leucine to proline at codon 575. The specific mutation on DMD c.1724T>C (p.Leu575Pro) is listed in the Clinvar database as a variant of unknown significance. Our report provides contributing evidence that this genetic alteration should be classified as pathogenic. Case Information: Our 3 patients above the age of 2 years presented with elevated creatine kinase levels, myalgia after exercise, and occasional muscle cramping. Our 2 patients below the age of 2 years presented with elevated creatine kinase levels and no other findings. This mutation has been reported before, with 3 prior patients presenting with similar clinical findings of myalgia, myoglobinuria, and occasional muscle cramping. Some similarities among all 8 patients include elevated creatine kinase levels, no muscle weakness, no calf hypertrophy, and no Gower sign. Discussion: Of note, these patients can present initially with elevated liver function enzymes, as seen with 1 of our patients, and our report raises awareness that dystrophinopathies should be considered before undergoing costly gastrointestinal testing. Two of the 8 patients presented with neuropsychiatric disorders: 1 with attention-deficit/hyperactivity disorder (ADHD) and 1 with autism. This suggests that ADHD and autism may be a presenting feature of dystophinopathies, and creatine kinase levels should be considered in their evaluation. This report elucidates the clinical presentation of the mutation on DMD c. 1724T>C.