Duchenne Muscular Dystrophy (DMD)

Muscular dystrophy is the name given to a group of more than 30 genetic diseases characterized by progressive muscular weakness and atrophy.¹

The muscular dystrophies are classified in 9 major groups, which differ in regard to muscle weakness and age at the onset of symptoms. Duchenne muscular dystrophy (DMD) is the most common form of childhood muscular dystrophy.

Other important entities included in the differential diagnosis of muscular dystrophy are Becker muscular dystrophy (BMD), Emery-Dreifuss muscular dystrophy, limb-girdle muscular dystrophy (LGMD), and spinal muscular atrophy (SMA).²

All of these have some features similar to those of DMD as well as traits that distinguish them from DMD.

Becker Muscular Dystrophy

The main similarities between BMD and DMD are calf muscle pseudohypertrophy, markedly elevated serum levels of creatine kinase, and X-linked inheritance.³

Both BMD and DMD are caused by a mutation in the DMD gene, located on the X chromosome. The main difference between them relates to the reading frame of the DMD gene. In DMD, the mutation disrupts the reading frame; as a result, no dystrophin protein forms in cells (dystrophin is encoded by the DMD gene). In BMD, the reading frame is maintained and some dystrophin protein forms in cells; however, it is not of full length, although still functional.⁴

Because the gene is located on the X chromosome, the disease generally affects boys who inherit a faulty copy of the gene from their mother. Girls are usually not affected or have relatively mild symptoms because the paternal X chromosome carries a healthy DMD gene that can compensate for the mutated one. However, females with mutated copy of the DMD gene act as carriers and may have muscle weakness and cramping. Moreover, they have increased risk of developing heart abnormalities including cardiomyopathy.⁵

The main difference between BMD and DMD is that in BMD muscle weakness usually progresses more slowly, so that the disease is diagnosed later, whereas in DMD, symptoms become apparent much earlier, when the patient is between the ages of 3 and 5 years.⁶ 

In BMD, the frequency of cardiac involvement is between 60% to 75%.⁷

Another difference between BMD and DMD relates to prevalence; DMD is more common, and BMD is rarer. DMD can affect intelligence, whereas BMD usually does not. Life expectancy also differs in these 2 diseases; patients with DMD live for approximately 15 to 20 years after the diagnosis, whereas those with BMD may live another 25 to 30 years. Patients with BMD do not have early contracture, unlike those with DMD. Patients with DMD usually lose the ability to ambulate before the age 12 years, whereas those with BMD usually maintain ambulation into their fourth decade.⁸

Emery-Dreifuss Muscular Dystrophy

Similarities between Emery-Dreifuss muscular dystrophy and DMD include progressive muscle weakness, elbow and ankle contracture, and cardiomyopathy.⁹ 

The main difference is that calf pseudohypertrophy does not occur in Emery-Dreifuss muscular dystrophy. Moreover, the serum creatine kinase levels are normal in Emery-Dreifuss muscular dystrophy. Elbow and ankle contracture develop earlier than in DMD. 

Limb-Girdle Muscular Dystrophy

Both LGMD and DMD are characterized by progressive motor weakness. As in Emery-Dreifuss muscular dystrophy, calf muscle pseudohypertrophy is absent. The serum creatine kinase levels are only mildly elevated, although they are much higher in autosomal-recessive forms of the disease than autosomal-dominant forms.¹⁰

Spinal Muscular Atrophy

SMA is also characterized by hypotonia and muscle weakness, but unlike in muscular dystrophy, these are caused by the progressive degeneration of alpha motor neurons.¹¹

The main similarity between SMA and DMD is proximal muscle weakness. However, in SMA, the onset of weakness is usually earlier in childhood.

SMA is characterized by the absence of deep tendon reflexes and by tongue fasciculations, which are not features of DMD. Moreover, calf pseudohypertrophy is absent, and serum creatine kinase levels are normal.²

Other Conditions Included in the Differential Diagnosis

The differential diagnosis for a patient presenting with muscle weakness in early infancy also includes the congenital myopathies and myoneural junction disorders.¹²

The main difference between the congenital myopathies and muscular dystrophies is that in the former, neonatal muscle weakness is present but usually not progressive, whereas in the latter, muscle weakness and atrophy are progressive and worsen with age.

Muscular weakness in the congenital myopathies may be caused by a genetic or metabolic disorder. The most common congenital myopathies are central core myopathy, nemaline rod myopathy, and centronuclear myopathy. These may develop as a result of disordered carbohydrate or fat metabolism.

Myoneural junction disorders are very rare but are part of the differential diagnosis in infants presenting with muscle weakness. They include congenital myasthenia gravis and infant botulism.

References

1. Muscular dystrophy: hope through research. National Institute of Neurological Disorders and Stroke. Modified February 25, 2021. Accessed June 22, 2021.
2. Prabhakar MM. Muscular dystrophies. SlideShare. Posted January 30, 2017. Accessed June 22, 2021.
3. Thada PK, Bhandari J, Umapathi KK. Becker muscular dystrophy. StatPearls. Updated November 23, 2020. Accessed June 22, 2021. 
4. Gao Q, McNally EM. The dystrophin complex: structure, function and implications for therapy. Compr Physiol. 2015;1;5(3):1223-1239. doi:10.1002/cphy.c140048
5. Duchenne and Becker muscular dystrophy. MedlinePlus. Updated August 18, 2020. Accessed June 22, 2021.
6. Duchenne muscular dystrophy. National Organization for Rare Disorders. Published 2016. Accessed June 22, 2021.
7. Ho R, Nguyen ML, Mather P. Cardiomyopathy in becker muscular dystrophy: Overview. World J Cardiol. 2016;8(6):356-361. doi:10.4330/wjc.v8.i6.356
8. Andrews JG, Wahl RA. Duchenne and Becker muscular dystrophy in adolescents: current perspectives. Adolesc Health Med Ther. 2018;9:53-63. doi:10.2147/AHMT.S125739
9. Emery Dreifuss muscular dystrophy. National Organization for Rare Disorders. Published 2015. Accessed June 22, 2021.
10. Limb-girdle muscular dystrophies. National Organization for Rare Disorders. Published 2012. Accessed June 22, 2021.
11. D’Amico A, Mercuri E, Tiziano FD, Bertini E. Spinal muscular atrophy. Orphanet J Rare Dis. 2011;6:71. doi:10.1186/1750-1172-6-71
12. Congenital muscular dystrophy. StatPearls. Accessed June 22, 2021. 

Article reviewed by Debjyoti Talukdar, MD on July 1, 2021.

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Ozge Ozkaya, MSc, PhD

Özge’s background is in research; she holds a MSc. in Molecular Genetics from the University of Leicester and a PhD. in Developmental Biology from the University of London. Özge worked as a bench scientist for six years in the field of neuroscience before embarking on a career in science communication. She worked as the research communication officer at MDUK, a UK-based charity that supports people living with muscle-wasting conditions, and then a research columnist and the managing editor of resource pages at BioNews Services before joining Rare Disease Advisor.