Duchenne Muscular Dystrophy (DMD)

Muscular dystrophy is a group of disorders characterized by progressive muscle weakness and atrophy. There are 9 main types of muscular dystrophy that differ in terms of affected muscles, age of onset, and progression rate of symptoms. These types are congenital muscular dystrophy, Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), facioscapulohumeral muscular dystrophy (FSHD), limb-girdle muscular dystrophy, Emery-Dreifuss muscular dystrophy, distal muscular dystrophy, myotonic muscular dystrophy, and oculopharyngeal muscular dystrophy.¹

Muscle weakness and atrophy, the main characteristic of all types of muscular dystrophy, can lead to motor delays and mobility issues. The disease is also associated with other comorbidities such as fatigue and cognitive impairments.²

Motor Delays

Motor delays are common among patients affected by muscular dystrophy. Patients with some types of muscular dystrophy display a characteristic waddling gait. Patients may also experience frequent falling, difficulty running and jumping, difficulty rising from a sitting or lying position, and walking on toes. Symptoms of muscular dystrophy can appear at birth as in the case of congenital muscular dystrophy or much later in life like in the case of FSHD.³ 

The onset of walking can also be delayed in children with DMD, and research has attributed this to cognitive delay.⁴

In later stages of severe muscular dystrophy, patients usually lose ambulation and may need to rely on a wheelchair for mobility.

Fatigue

Fatigue is a common comorbidity in patients with muscular dystrophy. Fatigue can either be acute or chronic. Muscle weakness, respiratory insufficiency, sleep disturbances, and cardiac problems can all contribute to fatigue.⁵

In DMD and limb-girdle muscular dystrophy type 2E, the alteration of dystrophin and sarcoglycan complex as well as neuronal nitric oxide synthase depletion might correlate with fatigue following exercise.

Fatigue is also a common complaint among patients with myotonic dystrophy. Fatigue and daytime sleepiness in these patients can be explained by brain involvement and depressed mood.

Brain Comorbidities 

Patients with DMD may be at an increased risk of cognitive and developmental delays including language acquisition, which are associated with significant impairments in later cognitive functioning.⁶

The exact role of dystrophin in the brain and how mutations in the dystrophin-encoding DMD gene lead to brain problems is not fully understood. However, it is thought that dystrophin may be involved in executive functions, perception, and information processing.⁷ 

Mutations disrupting the shorter C-terminus dystrophin isoforms seem to be associated with significant psychiatric comorbidities compared to mutations in the 5’ end of the DMD gene. Moreover, patients with mutations downstream of exon 30 seem to be at a higher risk of having coexistent neuropsychiatric symptoms.⁸

Research has also shown that DMD patients have smaller total brain volume, which may contribute to the relatively high rate of neuropsychiatric disorders. Patients also often exhibit attention-deficit and hyperactivity disorder, learning and intellectual disabilities, anxiety, depression, and autism spectrum disorders.⁹

Moreover, the prevalence of epilepsy is also increased in patients with DMD. The age of onset of epilepsy ranges between ages 3 months to 16 years, and seizures mostly include focal seizures, generalized tonic-clonic seizures, or absence seizures.¹⁰ 

Similarly, patients with BMD are at high risk of developing psychiatric disorders. Research has shown that BMD can cause brain atrophy, which can contribute to the development of psychiatric problems.¹¹

Psychological support should be provided throughout the life of DMD and BMD patients and can increase their quality of life. 

Other Comorbidities

Other comorbidities often observed in patients with DMD include constipation, obesity, and kidney stones. According to one study that aimed to describe the secondary conditions among patients with DMD, 31.7% of patients were affected by constipation, and 19.5% were obese.¹²

Obesity itself can cause other comorbidities in patients with DMD including short stature, pubertal delay, and adrenal insufficiency, as well as complications such as glucose intolerance, hyperglycemia, hypertension, dyslipidemia, and gastrointestinal reflux disease.

The weight status of the patients should be regularly monitored, and both weight and body mass index (BMI) should be plotted on a curve to determine the percentile for age. If weight for age or BMI scores are increased by more than 0.5 between visits and/or if BMI is higher than the 85th percentile, an intensive interdisciplinary weight management program should be followed.¹³

Kidney stones are more common among nonambulatory patients than ambulatory ones, as are anxiety and depression. Other kidney dysfunctions that are common in patients with DMD include mild proteinuria, hypercalciuria, hypocalciuria, and hyperphosphaturia. These could be the result of long-term exposure to components released from damaged muscles.¹⁴

References

1. Types of muscular dystrophy and neuromuscular diseases. University of Rochester Medical Center. Accessed June 1, 2021.
2. Rae MG, O’Malley D. Cognitive dysfunction in Duchenne muscular dystrophy: a possible role for neuromodulatory immune molecules. J Neurophysiol. 2016 Sep 1; 116(3): 1304–1315. doi:10.1152/jn.00248.2016
3. Muscular dystrophy. Mayo Clinic. Accessed June 1, 2021.
4. Mirski KT, Crawford TO. Motor and cognitive delay in Duchenne muscular dystrophy: implication for early diagnosis. J Pediatr. 2014;165(5):1008-10. doi:10.1016/j.jpeds.2014.07.006  
5. Angelini C, Tasca E. Fatigue in muscular dystrophies. Neuromuscul Disord. 2012;22(3-3):S214-S20. doi:10.1016/j.nmd.2012.10.010
6. Cyrulnik SE, Fee RJ, De Vivo DC, Goldstein E, Hinton VJ. Delayed developmental language milestones in children with Duchenne’s muscular dystrophy. J Pediatr. 2007;150(5):474-78. doi:10.1016/j.jpeds.2006.12.045
7. Caudal D, François V, Lafoux A, et al. Characterization of brain dystrophins absence and impact in dystrophin-deficient Dmdmdx rat model. PLOS One. 2020;15(3):e0230083. doi: 10.1371/journal.pone.0230083
8. Ricotti V, Scoto M, Mandy W, et al. Neuropsychiatric comorbidities in Duchenne muscular dystrophy. Neuromuscul Disord. 2013;23(9-10):752-53. doi:10.1016/j.nmd.2013.06.418
9. Colvin MK, Poysky J, Kinnett K, et al. Psychosocial management of the patient with Duchenne muscular dystrophy. Pediatrics. 2018;142(Suppl 2):S99-S109. doi:10.1542/peds.2018-0333L
10. Pane M, Messina S, Bruno C, et al. Duchenne muscular dystrophy and epilepsy. Neuromuscul Disord. 2013;23(4):313-15. doi:10.1016/j.nmd.2013.01.011
11. Mori-Yoshimura M, Mizuno Y, Yoshida S, et al. Psychiatric and neurodevelopmental aspects of Becker muscular dystrophy. Neuromuscul Disord. 2019;29(12):930-39. doi:10.1016/j.nmd.2019.09.006
12. Latimer R, Street N, Conway KC, et al. Secondary conditions among males with Duchenne or Becker muscular dystrophy. J Child Neurol. 2017;32(7):663-70. doi:10.1177/0883073817701368
13. Weber DR, Hadjiyannakis S, McMillan HJ, Noritz G, Ward LM. Obesity and endocrine management of the patient with Duchenne muscular dystrophy. Pediatrics. 2018;142(Suppl 2):S43-S52. doi:10.1542/peds.2018-0333F
14. Kutluk MG, Doğan ÇS. Kidney involvement and associated risk factors in children with Duchenne muscular dystrophy. Pediatr Nephrol. 2020;35(10):1953-58. doi:10.1007/s00467-020-04587-3

Article reviewed by Debjyoti Talukdar, MD on July 1, 2021.

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Ozge Ozkaya, MSc, PhD

Özge’s background is in research; she holds a MSc. in Molecular Genetics from the University of Leicester and a PhD. in Developmental Biology from the University of London. Özge worked as a bench scientist for six years in the field of neuroscience before embarking on a career in science communication. She worked as the research communication officer at MDUK, a UK-based charity that supports people living with muscle-wasting conditions, and then a research columnist and the managing editor of resource pages at BioNews Services before joining Rare Disease Advisor.