Challenges in DMD: Understanding the Height Factor

Growth Challenges in DMD: Understanding the Height Factor

Duchenne muscular dystrophy (DMD) is a genetic, pediatric disease marked by progressive muscle degeneration and weakness. It primarily affects males and leads to a lack of dystrophin, which is critically involved in muscle strength and stability. Unfortunately, there is no cure; children diagnosed with DMD have a short life expectancy, often suffering from heart or respiratory failure before or during their 30s.

The musculoskeletal effects of DMD significantly impair patients’ motor skills, causing substantial impacts on quality of life. Additionally, short stature and low BMI are common due to impaired growth and development arising from reduced muscle mass, which hinders bone turnover. This is typically exacerbated by glucocorticoid (GC) treatment, a cornerstone of DMD management.

GC therapy, such as prednisone or deflazacort, is used to improve muscle strength, prolong ambulation, enhance pulmonary function, and reduce inflammation to aid muscle repair. However, chronic GC use can suppress growth hormone production, contributing to stunted growth. Whether growth suppression should be mitigated or encouraged remains up for debate.

Findings on Height Differences in DMD Patients

Research suggests that the type, dosage, and duration of GC therapy influences the degree of growth impairment in DMD patients. For example, an alternating prednisone regimen has been shown to have no apparent side effects on weight and height in the ambulatory phase of DMD. Additionally, growth hormone therapy has demonstrated enhanced growth velocity in DMD patients without affecting motor, cardiac, or pulmonary functions.

Interestingly, research shows shorter stature in patients with DMD may have clinical benefits. Children with DMD are capable of walking when they’re young, but they lose that ability as they grow, signaling a loss of function with height.

An early study found a significant correlation between height and clinical outcomes in male children with DMD. Related studies have supported this over the years, suggesting that inhibiting growth could be effective in slowing DMD progression. This phenomenon is likely due to the mechanical strain associated with exponential growth of load per muscle fiber, which causes structural damage and accelerating loss of muscle fibers. Consequently, maintaining a controlled weight and implementing non-weight-bearing exercises can help reduce stress on muscle fibers and preserve their function.

DMD presents unique emotional and physical challenges for both patients and caregivers. Treatment plans should be tailored to individual needs, balancing the benefits of GC therapy with the potential impact on growth. As research evolves, a comprehensive approach that considers both quality of life and disease progression remains essential.

References:

Bodor, M., & McDonald, C. M. (2013). Why short stature is beneficial in Duchenne muscular dystrophy. Muscle Nerve, 48(3), 336-342. https://doi.org/10.1002/mus.23793

Lavi, E., Cohen, A., Libdeh, A. A., Tsabari, R., Zangen, D., & Dor, T. (2023). Growth hormone therapy for children with Duchenne muscular dystrophy and glucocorticoid induced short stature. Growth Horm IGF Res, 72-73, 101558. https://doi.org/10.1016/j.ghir.2023.101558

Nagel, B. H., Mortier, W., Elmlinger, M., Wollmann, H. A., Schmitt, K., & Ranke, M. B. (1999). Short stature in Duchenne muscular dystrophy: a study of 34 patients. Acta Paediatr, 88(1), 62-65.

ten Dam, K., de Groot, I. J., Noordam, C., van Alfen, N., Hendriks, J. C., & Sie, L. T. (2012). Normal height and weight in a series of ambulant Duchenne muscular dystrophy patients using the 10 day on/10 day off prednisone regimen. Neuromuscul Disord, 22(6), 500-504. https://doi.org/10.1016/j.nmd.2012.01.005

Ward, L. M., & Weber, D. R. (2019). Growth, pubertal development, and skeletal health in boys with Duchenne Muscular Dystrophy. Curr Opin Endocrinol Diabetes Obes, 26(1), 39-48. https://doi.org/10.1097/MED.0000000000000456

Zatz, M., Rapaport, D., Vainzof, M., Rocha, J. M., Pavanello, R. e. C., Colletto, G. M., & Peres, C. A. (1988). Relation between height and clinical course in Duchenne muscular dystrophy. Am J Med Genet, 29(2), 405-410. https://doi.org/10.1002/ajmg.1320290223