Science is rewriting the Duchenne muscular dystrophy lifespan. Care must catch up
Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy, affecting 1 in 3500-6000 boys. It is caused by changes in the dystrophin gene, located on the X chromosome, which results in progressive muscle weakness.
Boys with DMD typically present between three and five years of age, with difficulty running and climbing stairs, frequent falls and keeping up with peers. Boys will typically lose the ability to walk independently by 10-13 years.
As DMD advances, individuals experience progressive lung or heart dysfunction as well as loss of arm function and gastrointestinal complications. Without medical management, most young people with DMD would not live past their teenage years.
DMD was first characterised in the nineteenth century by Guillaume-Benjamin-Amand Duchenne, however, the genetic cause was not identified until the 1980s. During the time, the management of DMD was purely symptomatic, including interventions such as callipers to help with standing and antibiotics to manage respiratory illness.
But in the past two decades there has been significant shifts in the medical management of DMD, such as the use of corticosteroids – which have been shown to improve muscle strength and increase life expectancy.
Other changes include proactive management of heart and lungs with angiotensin-converting enzyme inhibitors (ACE-I) and non-invasive ventilation, respectively, as well as the publication of the first international practice guidelines for DMD in 2009.
With these shifts in practice, there has been a recent focus on understanding the impact of improved care on life expectancy in DMD.
Two recent analyses have pooled data from multiple studies to provide estimates of life expectancy in DMD based on the available scientific literature.
In these analyses, life expectancy was estimated at 23·7 and 22 years. However, there was only one study from Australia included, published in 1995, that looked at life expectancy in individuals with DMD who had spinal surgery.
We have also identified one other study, published in 1982, describing life expectancy in individuals with DMD in Western Australia in which the mean age of death was 20, with half of the cohort surviving beyond 21.
Beyond these two studies, there is very limited information describing life expectancy and the natural history of DMD in Australia.
To address this important gap, we assembled a group of health professionals and researchers from Monash University, Murdoch Children’s Research Institute, the Royal Children’s Hospital, Austin Health and St Vincent’s Hospital, Melbourne.
We aimed to describe changes in the clinical management and survival in individuals with DMD over time as well as the effect of modern clinical management on survival.
To do this, we identified 356 individuals with DMD who attended the Royal Children’s Hospital between 1973-2019, and collected information from medical records. We then linked this to information from medical records from adult health services.
To look at the data over time, we grouped individuals with DMD based on their decade of birth, from those born before 1970, 1970-1979, 1980-1989, 1990-1999, 2000-2009 and 2010-2019.
Our results showed that median life expectancy for individuals with DMD has increased from 18.2 years for those born before 1970 to 24 years in individuals born 1990-1999. The likelihood of survival to 20 has also steadily increased across this period. Most young people with DMD in the two most recent birth decades were still alive, so we were unable to determine life expectancy for these groups.
Across the birth cohorts, we observed increasing use of corticosteroids, ACE-I and respiratory support. Increased life expectancy was observed in individuals receiving these therapies. Another key finding was a decrease in the age of diagnosis across the decades.
This unique cohort represents the largest DMD cohort investigating survival from the southern hemisphere and one of the largest and oldest DMD cohorts internationally.
There have only been five other studies investigating life expectancy with a larger sample size and one study with an earlier time period. However, we were unable to determine key outcomes, such as survival, for the two most recent birth decades because they were too young when we conducted the study.
It will be important to follow these younger cohorts to fully understand the impact of modern management on survival in DMD. This will be an important role of the Australian Neuromuscular Disease Registry, which was established in its current iteration in 2020.
Looking back at the history of DMD in Australia has several key implications.
Firstly, adult care for individuals with DMD in Australia can be fragmented. As individuals with DMD are surviving well into adulthood, we need to advocate strongly for streamlined services to provide best practice, multidisciplinary care to adults with DMD.
Secondly, as gene and genetic therapies for DMD progress through clinical trial pipelines, it is likely that at least some of these therapies will be evaluated by the TGA for approval in Australia in the foreseeable future.
This natural history data will be an important historical comparison for post approval therapy surveillance.
Finally, this data contributes important information on the potential impact of an early diagnosis in DMD to the discussion on newborn screening for DMD.
What was once a disease of childhood, DMD is now clearly changing with a new population of adults emerging. All levels of the health system, from policymakers to health professionals need to be aware of the changing natural history and promote best practice care for individuals with DMD across the lifespan.
