G.P.82 ‘Double Trouble’: Diagnostic challenges in DMD in patients with an additional hereditary skeletal dysplasia

Abstract Duchenne muscular dystrophy (DMD) is an X-linked disease that is caused by mutations in the dystrophin gene and affects one in 3600–6000 live male births. DMD is characterized by progressive weakness leading to a loss of ambulation, respiratory insufficiency, cardiomyopathy and scoliosis. Boys typically present at 3–5 years of age with evidence of proximal weakness and calf hypertrophy. Here we describe the unusual and complicated clinical phenotype of three patients with hereditary skeletal dysplasias in whom an additional diagnosis of DMD was then established. Two unrelated boys presented each with a diagnosis of osteogenesis imperfecta (types 1 and 4) due to point mutations in COL1A1, and were both subsequently found to have a 1 bp frameshift deletion in the dystrophin gene at age 3 and age 15, respectively. The third patient had an established diagnosis of inherited pseudoachondroplasia and was found to have a deletion of exons 48–50 in dystrophin at age 8 years. We discuss the atypical clinical presentation caused by the concomitant presence of two conditions affecting the musculoskeletal system, emphasizing features that may confound the presentation of a well-characterized disease like DMD. Additional case series of patients with DMD and a secondary genetically confirmed condition are necessary to establish the natural history in this “double trouble” patient population. The recognition and accurate diagnosis of patients with two independent genetic disease processes is essential for management, prognosis, proper genetic recurrence risk information, and discussion regarding potential therapeutic interventions.