Duchenne Muscular Dystrophy (DMD)

Muscular dystrophy is the name given to a group of genetic diseases characterized by progressive muscle weakness and wasting. There are several types of muscular dystrophy, all with a different genetic cause.1 

Most of the literature focuses on risk factors associated with the onset and natural progression of Duchenne and Becker muscular dystrophies. A 2017 study found that there are 3 main risk factors associated with poor outcome in patients with Duchenne muscular dystrophy (DMD). These are low body mass index (BMI), poor lung function, and high cardiac biomarkers like N‐terminal pro‐brain natriuretic peptide.2

Some data is also available on risk factors for sudden death in patients suffering with neuromuscular disease like myotonic dystrophy, the most common type of muscular dystrophy in adults.3

Muscular Dystrophy Statistics

Duchenne muscular dystrophy is a rare genetic disease, with a birth prevalence of 1 in 3500 to 1 in 5000 male live births.4

A 2015 study published in Pediatrics that looked at the prevalence of Duchenne and Becker muscular dystrophies found that the estimated combined prevalence of both diseases was 1 in 7250 males aged 5 to 24. According to the study, the prevalence of DMD was 3 times higher than that of Becker muscular dystrophy (BMD).5

The same study found that by the end of 2007, more than 85% of patients with Duchenne and Becker muscular dystrophies born 15 to19 years earlier were still alive, but only 58% of those born 20 to 24 years earlier were still alive.

It is estimated that muscular dystrophies as a whole affect around 250,000 people in the US. According to a 2010 study, muscular dystrophies were associated with approximately 1 in 2500 deaths overall. The overall age-adjusted muscular dystrophy-associated mortality rate was 0.347 per 100,000 persons per year.6

In recent years, improvements in ventilator care and spinal surgery increased the life expectancy of patients with DMD and changed the cause of death in most cases from respiratory complications to cardiomyopathy.2

Risk Factors Associated With Poor Outcome in DMD

A 2017 study published in the Journal of the American Heart Association analyzed the predictors of death in adults with DMD-associated cardiomyopathy in 43 patients with DMD. The study found that low body mass index (BMI), poorer lung function, and higher levels of biomarkers of heart damage were associated with a higher risk of death.2

The study found that patients who died early had a lower BMI (17.3 kg/m2 on average) compared to those who survived (25.8 kg/m2 on average). The researchers argued that a lower BMI (underweight) could be a manifestation of overall disease state. 

Another common trait among patients who died earlier was poor lung function. Accordingly, the degree of respiratory muscle weakness was significantly worse with lower maximum inspiratory pressure (MIP) for patients who died earlier than in those who survived. There was also a trend towards worse maximal expiratory pressure in those who died early.

Finally, patients who died early had significantly higher levels of NT‐proBNP (N‐terminal pro‐brain natriuretic peptide), a marker of congestive heart failure, compared to those who survived. 

Genetic Risk Factors 

A systematic review of risk factors associated with muscular dystrophies published in Neurotoxicology identified a number of genetic polymorphisms that could affect disease progression in DMD and BMD patients.7

One of these was a single nucleotide polymorphism in the promoter region of the secreted phosphoprotein 1 (SPP1) osteopontin genotype, which was associated with greater muscle weakness and earlier loss of ambulation.8

Another genetic modifier of disease progression in DMD was the LTBP4 gene, which encodes the latent transforming growth factor (TGF) β-binding protein. TGFβ signaling plays a role in muscle function and regeneration, and research has shown that patients homozygous for the IAAM LTBP4 haplotype lost ambulation later than those with the VTTT haplotype (heterozygous or homozygous).9

Risk Factors for Sudden Death in Myotonic Dystrophy

Sudden death, which is defined as death occurring in a stable patient within 1 hour of symptom onset, can occur in patients with myotonic dystrophy type 1, a type of muscular dystrophy that affects both skeletal and smooth muscle. This is usually the result of cardiac-conduction abnormalities.

A study published in 2008 in the New England Journal of Medicine reported that a severe electrocardiogram (ECG) abnormality and a clinical diagnosis of atrial tachyarrhythmia were independent risk factors for sudden death in patients with myotonic dystrophy type 1.3

Other Factors

There may be other factors such as biological, socioeconomic, environmental, psychosocial, and comorbid factors that have an impact on the onset and natural progression of muscular dystrophies. More research is needed to identify such factors and better understand their influence on disease progression and epidemiology.


  1. Overview – muscular dystrophy. NHS. Accessed June 23, 2021.  
  2. Cheeran D, Khan S, Khera R, et al. Predictors of death in adults with Duchenne muscular dystrophy-associated cardiomyopathy. J Am Heart Assoc. 2017;6(10):e006340. doi:10.1161/JAHA.117.006340
  3. Groh WJ, Groh MR, Saha C, et al. Electrocardiographic abnormalities and sudden death in myotonic dystrophy type 1. N Engl J Med. 2008;358(25):2688-2697. doi:10.1056/NEJMoa062800
  4. Yiu EM, Kornberg AJ. Duchenne muscular dystrophy. J Paediatr Child Health. 2015;51(8):759-764. doi:10.1111/jpc.12868
  5. Romitti PA, Zhu Y, Puzhankara S, et al.; MD STARnet. Prevalence of Duchenne and Becker muscular dystrophies in the United States. Pediatrics. 2015;135(3):513-521. doi:10.1542/peds.2014-2044
  6. Kenneson A, Vatave A, Finkel R. Widening gap in age at muscular dystrophy-associated death between blacks and whites, 1986–2005. Neurology. 2010;75(11):982–989. doi:10.1212/WNL.0b013e3181f25e5b
  7. Barakat-Haddad C, Shin S, Candundo H, Lieshout PV, Martino R. A systematic review of risk factors associated with muscular dystrophies. Neurotoxicology. 2017;61:55-62. doi:10.1016/j.neuro.2016.03.007
  8. Pegoraro E, Hoffman EP, Piva L, et al.; Cooperative International Neuromuscular Research Group. SPP1 genotype is a determinant of disease severity in Duchenne muscular dystrophy. Neurology. 2011;76(3):219–226. doi:10.1212/WNL.0b013e318207afeb
  9. Flanigan KM, Ceco E, Lamar KM, et al.; United Dystrophinopathy Project. LTBP4 genotype predicts age of ambulatory loss in Duchenne muscular dystrophy. Ann Neurol. 2013;73(4):481-488. doi: 10.1002/ana.23819

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