Review on Short Stature and Delayed Puberty in Duchenne Muscular Dystrophy Patients

Patrícia Silva, PhD avatar

by Patrícia Silva, PhD |

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Duchenne gene therapy

Researchers at Royal Victoria Infirmary and the Institute of Genetic Medicine in the United Kingdom recently conducted a review on the short stature and delayed puberty often seen in patients with Duchenne muscular dystrophy (DMD). The study was published in the journal Archives of Disease in Childhood and is entitled “Short stature and pubertal delay in Duchenne muscular dystrophy”.

DMD is an inherited disorder caused by a defective gene called dystrophin. It is characterized by a rapid progressive skeletal muscle weakness caused by chronic inflammation and the degeneration of muscle cells and tissue, which can compromise locomotion and the respiratory function, leading to breathing complications and cardio-respiratory failure. DMD has a rapid progression and affects mainly boys. Most DMD patients require a wheelchair by the age of 12. Although there is no cure, multidisciplinary care and the use of corticosteroids have enabled DMD patients to live into their 30s.

Corticosteroids are the only therapeutic agents proven to stabilize muscle strength for this condition, and are chosen as the primary treatment option for DMD. The exact mechanism of action of corticosteroids in DMD is not clear, but most likely is not limited to their anti-inflammatory properties. However, the daily use of corticosteroids can induce serious side effects in DMD patients, including a slower growth rate and pubertal delay.

Children with DMD are often shorter than healthy children, and steroid therapy exacerbates this difference. The reasons underlying this growth failure are poorly elucidated. An ongoing clinical study is analyzing different regimens of corticosteroid therapy and its impact on efficacy and long-term effects. It is thought that daily regimens might be more effective in slowing disease progression but, on the other hand, more likely to have unfavorable effects on growth in comparison to intermittent regimens.

The mechanism underlying pubertal delay in DMD patients under corticosteroid therapy is not clear. Interestingly, DMD patients who are not under corticosteroid treatment tend to progress through puberty normally, suggesting that it is solely the treatment and not the disease the cause of this delay in puberty.

According to the authors, in the United Kingdom it is estimated that at least 10% of all the children require some form of corticosteroid treatment during childhood. The balance between the benefits of corticosteroid therapy and the potential adverse effects needs to be assessed individually on each case. However, different from other childhood diseases like asthma or inflammatory bowel disease, taper and weaning corticosteroid treatment is not part of the DMD disease management. DMD patients are expected to continue on steroid therapy throughout their lives, not only because of the potential benefits in motor function, but also on the vital respiratory and cardiac function.

There is no consensus in terms of pharmacological strategies for the treatment of short stature and pubertal delay in DMD. It is known that the growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are affected in DMD patients, but there is limited and conflicting data regarding the use of GH-based therapies to improve muscle function and strength. IGF-1 is currently being assessed in a pilot study for its impact on muscle function and growth rate in DMD, and preliminary results indicate a height gain in the group under IGF-1 treatment with only mild adverse events. There is also no consensus in the use of testosterone treatment in DMD patients.

The team suggests that further studies should be conducted before a therapy can be recommended for the treatment of short stature and pubertal delay in those suffering with DMD.