Missed Opportunities for Duchenne Muscular Dystrophy

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DMD, Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy (DMD) continues to challenge affected boys and their families because it causes progressive weakness in children who were seemingly normal as infants and toddlers. The discovery of mutations in the dystrophin gene more than 2 decades ago¹ raised hopes for improved diagnosis and treatment, some of which have been fulfilled. For almost all patients, the diagnosis can be confirmed by genetic testing, largely obviating the need for muscle biopsy. The survival rate has shown significant improvement, with now more than half of the patients surviving past age 25 years,² largely as a result of proactive pulmonary and cardiac management. There is clear evidence for prednisone delaying the loss of motor function³ and reducing mortality rates.⁴ Animal models are available,⁵ and clinical trials are underway.⁶

Despite these advances, there has been no significant change over the past 20 years in the time from symptom onset to diagnosis. Ciafaloni et al⁷ report that 2.5 years go by on average until patients without known family history are given a definite diagnosis. It is not only surprising that it takes 2.5 years until a definite diagnosis is reached, but it is even more surprising that the interval has not decreased over the past 2 decades. The report by Ciafaloni et al⁷ suggests that there is room for improvement in appropriate training and ongoing medical education that would allow practitioners to make the diagnosis in a timelier manner. The initial screen, a blood test for creatine kinase, is widely available and inexpensive. In the past, one might have argued that little is gained by making an earlier diagnosis of an “incurable” disease. Today, effective treatments are available that can temporarily preserve motor function and prolong survival. There is therefore newfound urgency in making a correct diagnosis that will become more pressing as novel treatments enter clinical trials.

It is reasonable that practitioners do not include screening for a relatively rare and serious diagnosis such as DMD in the very first work-up for developmental delay in young boys when there is no calf hypertrophy, toe-walking or weakness. However, persistent delay should prompt screening earlier in the work-up so that a diagnosis can be made in less than 2.5 years from symptom onset. The report by Ciafaloni et al⁷ suggests that neurologists are more likely to order a creatine kinase test than primary care clinicians. Therefore educational initiatives aimed at primary care clinicians are a first approach to shorten the time to a correct diagnosis. Ciafaloni et al⁷ also report that about 15 additional affected maternal relatives were born in the interval from symptom onset to a definite diagnosis. These families did not have the genetic counseling opportunities that would have permitted an informed decision.

It is imperative that we improve translating scientific advances into medical practice for boys with DMD and their families by educating medical students, pediatricians, and other primary care practitioners that DMD is a readily diagnosable and treatable condition.

Although thought of as a muscle disease, a dystrophinopathy often affects language development early on in the course. Therefore checking for subtle signs of muscle weakness or calf hypertrophy and sending off a blood test for creatine kinase should be considered early on in the evaluation of any boy with not only motor, but also language delay. This simple message should be clearly incorporated in medical training and practice guidelines. Most experts support the implementation of newborn screening. However, until newborn screening is universally implemented, families depend on well-trained clinicians to afford them early access to a correct diagnosis and thus genetics counseling and treatment.

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References 

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