Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy, affecting nearly 16 of every 100,000 live male births in the United States. It causes progressive muscular damage and degeneration, which results in muscle weakness, loss of ambulation, motor delays, cardiomyopathy and reduced respiratory function.
Many boys present with clinical signs of DMD as early as 1 or 2 years of age. In many cases, pediatricians are the first to suspect the condition. Notes recently sat down with Partha Ghosh, MD, neurologist and neuromuscular disorder specialist at Boston Children’s Hospital to discuss symptoms of Duchenne muscular dystrophy, when to refer to a neuromuscular specialist, and diagnosis and treatment guidelines.
What symptoms might cause you to suspect DMD?
We ask pediatricians to suspect DMD in any boy that presents with delayed gross motor milestones, such as delayed walking, walking on their toes, frequent falling or difficulty climbing stairs. These symptoms can be easy to miss at age 1 1/2 to 2, but should be discernible by age 2.
Pediatricians should also suspect DMD if an incidental liver function test detects unusually high liver enzymes (in the hundreds) in an otherwise healthy patient. This occurs because the same enzyme that is released from the muscle is also released from the liver. If a patient has high liver enzymes with no other manifestations of liver disease, such as jaundice, you should suspect DMD.
What is the first step pediatricians should take if DMD is suspected?
If there is any suspicion of DMD, I would recommend testing for serum creatine kinase. This test is widely available and very inexpensive. While it doesn’t diagnose DMD, if it shows results in the thousands, then we would strongly suspect DMD. At this stage, we would suggest making a referral to neuromuscular center, such as ours.
We now have genetic treatments that are geared to treat some of the hundreds of different combinations of mutations for DMD.”
What additional steps do you take to diagnose DMD?
When children come to us, we do a more thorough exam and history. If it’s a boy with high creatine kinase and motor delays, our first suspicion would be DMD, and we would order genetic testing.
Because genetic testing is complicated we like to do it ourselves. The most common type of genetic mutation is deletion or duplication of the DMD gene, which picks up only about 70 percent of cases, so if we don’t add additional testing, like sequencing of the DMD gene, the diagnosis may be missed. If the genetic testing is not positive, we would look at other diagnoses, such as other forms of MD or other types of muscular disease.
We have genetic counselors here in neuromuscular clinic. They can discuss the test results, implications for future pregnancies and risks for other complications with the family.
Do you test female family members?
Girls cannot have Duchenne as such, but they can be manifesting carriers. If the test comes back positive for DMD and the mom is a carrier, she is at risk for having cardiac complications because DMD can affect the heart muscle in female carriers. In this case, we would strongly encourage her to be seen by a cardiologist.
We also want to test female siblings at some point after age 10 for risk of future pregnancy and cardiac involvement.
When do you start treatment?
We treat all DMD patients with corticosteroids, typically starting between 4 and 6 years of age, when the child’s motor symptoms plateau. This has been shown to prolong ambulation in DMD patients as well as have positive effects on cardiac and respiratory functions, upper limb function and scoliosis prevention if we start the medication early.
Are there any new treatments?
Yes, we now have genetic treatments that are geared to treat some of the hundreds of different combinations of mutations for DMD. For example, there is now an FDA-approved medication that can be given to 13 to 14 percent of patients with DMD. And there are also other forms of emerging genetic treatments which are in preclinical or trial phases of development. So, it is really important to learn the genetic mutation of DMD patients to tailor treatment. Our center is involved in several clinical trials in DMD patients and provides guidance and resources to the family.
How do you work with a child’s primary physician to coordinate care?
After a boy is diagnosed with DMD and is about to start steroids, we reach out to the pediatrician to find out if the child’s immunizations are up-to-date, and if not, to see if the child can get the vaccines before starting the steroids. In some cases, we may want to give the vaccinations a little early because if we start a high dose of steroids, some of the immunizations may not be effective. We may also need to do TB test before starting steroids, as they can cause TB to flare up in patients with latent TB.
We often work closely with the child’s primary physician when we start steroids, since there can be a lot of complications. We may also seek the PCP’s help regarding diet management, as steroids can cause weight gain, which can exacerbate the symptoms of DMD.
Lots of kids with DMD also have learning disabilities, autism and behavioral problems, so we often work with the PCP to help manage these conditions.
What is the long-term outlook for patients with DMD?
The long-term survival of patients with DMD has improved with multidisciplinary care and more targeted treatments. New guidelines for diagnosis and management of DMD were released this year, which outline best practices for caring for children with DMD.
At our specialized multidisciplinary DMD clinic, which is held on the first Monday of each month, patients meet with three doctors, a neuromuscular specialist, a pulmonologist and an orthopedic doctor or a physical medicine and rehabilitation specialist. We also coordinate care with the many other specialists patients need, from cardiology to endocrinology.
A physical therapist, social worker and genetic counselor are also present at each clinic to provide additional help to patients and their families, as is a Muscular Dystrophy Association (MDA) representative to assist families with finding community support.
About our expert: Partha Ghosh, MD, is a neurologist and neuromuscular disorder specialist at Boston Children’s Hospital and an assistant professor of neurology at Harvard Medical School.
Learn more about the Neuromuscular Center.