'Double trouble': diagnostic challenges in Duchenne muscular dystrophy in patients with an additional hereditary skeletal dysplasia.
Duchenne muscular dystrophy (DMD) is caused by mutations in Dystrophin and affects 1 in 3600-6000 males. It is characterized by progressive weakness leading to loss of ambulation, respiratory insufficiency, cardiomyopathy, and scoliosis. We describe the unusual phenotype of 3 patients with skeletal dysplasias in whom an additional diagnosis of DMD was later established. Two unrelated boys presented with osteogenesis imperfecta 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 years, respectively. The third patient had a diagnosis of pseudoachondroplasia caused by a mutation in the COMP gene and was found to have a deletion of exons 48-50 in Dystrophin at age 9. We discuss the atypical presentation caused by the concomitant presence of 2 conditions affecting the musculoskeletal system, emphasizing aspects that may confound the presentation of a well-characterized disease like DMD. Additional series of patients with DMD and a secondary inherited condition are necessary to establish the natural history in this "double trouble" population. The recognition and accurate diagnosis of patients with two independent genetic disease processes is essential for management, prognosis, genetic risk assessment, and discussion regarding potential therapeutic interventions.
National Institutes of Health, National Institute of Neurological Disorders and Stroke, Neurogenetics Branch, Bethesda, MD, United States.
Sandra
S
Donkervoort
Alice
A
Schindler
Carolina
C
Tesi-Rocha
Allison
A
Schreiber
Meganne E
ME
Leach
Jahannaz
J
Dastgir
Ying
Y
Hu
Ami
A
Mankodi
Kathryn R
KR
Wagner
Neil R
NR
Friedman
Carsten G
CG
Bönnemann
D000293:Adolescent; D001848:Bone Diseases, Developmental / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D064236:Cartilage Oligomeric Matrix Protein / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D024042:Collagen Type I / Q000235:genetics*; D000090602:Collagen Type I, alpha 1 Chain; D016189:Dystrophin / Q000235:genetics*; D005091:Exons / Q000235:genetics; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D010641:Phenotype; D017384:Sequence Deletion / Q000235:genetics; D014057:Tomography, X-Ray Computed
D064236:Cartilage Oligomeric Matrix Protein; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D016189:Dystrophin; C577553:TSP5 protein, human
Double trouble; Duchenne muscular dystrophy; Genetic counseling; Ostoegenesis imperfecta