Characteristics of a cohort of boys with Duchenne and Becker muscular dystrophies – a study from a single neuromuscular centre

Czech version

Authors: M. Rohlenová ¹; K. Machová ²; V. Stará ³; P. Hedvičáková ⁴; J. Zieg ³; T. Doušová ³; L. Fajkusová ⁵; J. Venclová-Žáčková ¹; O. Souček ³; J. Haberlová ¹
Authors‘ workplace: Klinika dětské neurologie, 2. LF UK a FN Motol, Praha ¹; UAM Czech Republic s. r. o., Praha ²; Pediatrická klinika, 2. LF UK a FN Motol, Praha ³; Ústav biologie a lékařské genetiky, 2. LF UK a FN Motol, Praha ⁴; Centrum molekulární biologie, a genové terapie, LF MU a FN Brno ⁵
Published in: Cesk Slov Neurol N 2020; 83/116(3): 305-314
Category: Original Paper
doi: https://doi.org/10.14735/amcsnn2020305

Overview

Aim: Description of natural course and variety of complications in Duchenne (DMD) and Becker (BMD) muscular dystrophies in childhood.

Patients and methods: Retrospective analysis of clinical and laboratory data with focus on muscular and extramuscular complications in 78 boys with dystrophinopathy (65 with DMD and 13 with BMD) followed up in our neuromuscular centre between 2004 and 2018.

Results: The incidence of secondary complications was negligible in boys with BMD. On the other hand, boys with DMD suffered from severe complications from their second decade of age. Overall 43 (66%) of the boys with DMD were treated with glucocorticoids. Glucocorticoid-treated boys lost ability to walk on average 1.3 years later than glucocorticoid-naive boys (P < 0.001). Moderate restrictive lung disease was diagnosed in 54% of boys with DMD older than 12 years of age, and loss of ability to walk was the most significant risk factor (P < 0.001). Decreased ejection fraction or myocardial fibrosis was found in 45% of boys older than 10 years of age. Boys with DMD had short stature in 40%, the incidence of which increased with age (P < 0.0001). Osteoporosis was diagnosed in 22% of boys with DMD, more often in the glucocorticoid-treated group than in glucocorticoid-naive group (P = 0.024). Transient proteinuria was described in 48% of boys with DMD. Psychological aberrations were described in 68% of boys with DMD.

Conclusion: This study describes the most extensive cohort of pediatric patients with dystrophinopathy in the Czech Republic and highlights the need of multidisciplinary care.

Keywords:

complications – osteoporosis – cardiomyopathy – Duchenne – Becker – multidisciplinary care – Proteinuria – muscular dystrophy – respiratory insufficiency

Sources

1. Birnkrant DJ, Bushby K, Bann CM et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet 2018; 17 (3): 251–267. doi: 10.1016/S1474-4422 (18) 30024-3.

2. Birnkrant DJ, Bushby K, Bann CM et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management. Lancet 2018, 17 (4): 347–361. doi: 10.1016/S1474-4422 (18) 30025-5.

3. Birnkrant DJ, Bushby K, Bann CM et al. Diagnosis and management of Duchenne muscular dystrophy, part 3: primary care, emergency management, psychosocial care, and transitions of care across the lifespan. Lancet 2018; 17 (5): 445–455. doi: 10.1016/S1474-4422 (18) 30026-7.

4. Kieny P, Chollet S, Delalande P et al. Evolution of life expectancy of patients with Duchenne muscular dystrophy at AFM Yolaine de Kepper centre between 1981 and 2011. Ann Phys Rehabil Med 2013; 56 (6): 443–454. doi: 10.1016/j.rehab.2013.06.002.

5. Wood CL, Straub V, Guglieri M et al. Short stature and pubertal delay in Duchenne muscular dystrophy. Arch Dis Child 2015; 101 (1): 101–106. doi: 10.1136/archdischild-2015-308654.

6. Bianchi, ML, Morandi L, Andreucci E et al. Low bone density and bone metabolism alterations in Duchenne muscular dystrophy: response to calcium and vitamin D treatment. Osteoporos Int 2011; 22 (2): 529–539. doi: 10.1007/s00198-010-1275-5.

7. Braat E, Hoste L, De Waele L et al. Renal function in children and adolescents with Duchenne muscular dystrophy. Neuromuscul Disord 2015; 25 (5): 381–387. doi: 10.1016/j.nmd.2015.01.005.

8. Ho R, Nguyen ML a Paul Mather P. Cardiomyopathy in becker muscular dystrophy: overview. World J Cardiol 2016; 8 (6): 356–361. doi: 10.4330/wjc.v8.i6.356.

9. Lomauro A, Romei M, Gandossini S et al. Evolution of respiratory function in Duchenne muscular dystrophy from childhood to adulthood. Eur Respir J 2018; 51 (2). pii: 1701418. doi: 10.1183/13993003.01418-2017.

10. Gloss D, Moxley RT, Ashwal S et al. Practice guideline update summary: corticosteroid treatment of Duchenne muscular dystrophy. Neurology 2016; 86 (5): 465–472. doi: 10.1212/WNL.0000000000002337.

11. Bushby K, Finkel R, Birnkrant DJ et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet 2010; 9 (1): 77. doi: 10.1016/S1474-4422 (09) 70271-6.

12. Duboc D, Meune C, Lerebours G et al. Effect of perindopril on the onset and progression of left ventricular dysfunction in Duchenne muscular dystrophy. J Am Coll Cardiol 2005; 45 (6): 855–857. doi: 10.1016/j.jacc.2004.09.078.

13. Duboc D, Meune C, Pierre B et al. Perindopril preventive treatment on mortality in Duchenne muscular dystrophy: 10 years’ follow-up. Am Heart J 2007; 154 (3): 596–602. doi: 10.1016/j.ahj.2007.05.014.

14. Bishop N, Arundel P, Clark E et al. Fracture prediction and the definition of osteoporosis in children and adolescents: the ISCD 2013 Pediatric Official Positions. J Clin Densitom 2014; 17 (2): 275–280. doi: 10.1016/j.jocd.2014.01.004.

15. Annexstad EJ, Fagerheim T, Holm I et al. Molecular and clinical characteristics of a national cohort of paediatric Duchenne muscular dystrophy patients in Norway. J Neuromuscul Dis 2019; 6 (3): 349–359. doi: 10.3233/JND-190402.

16. Markham LW, Spicer RL, Khoury PR et al. Steroid therapy and cardiac function in duchenne muscular dystrophy. Pediatr Cardiol 2005; 26 (6): 768–771. doi: 10.1007/s00246-005-0909-4.

17. Lomauro A, Romei M, Gandossini S et al. Evolution of respiratory function in Duchenne muscular dystrophy from childhood to adulthood. Eur Respir J 2018; 51 (2). pii: 1701418doi: 10.1183/13993003.01418-2017.

18. Liang WC, Wang CH, Chou PC et al. The natural history of the patients with Duchenne muscular dystrophy in Taiwan: a medical center experience. Pediatr Neonatol 2018; 59 (2): 176–183. doi: 10.1016/j.pedneo.2017.02.004.

19. Biggar WD, Harris VA, Eliasoph L et al. Long-term benefits of deflazacort treatment for boys with Duchenne muscular dystrophy in their second decade. Neuromuscul Disord 2006; 16 (4): 249–255. doi: 10.1016/j.nmd.2006.01.010.

20. Lamb M, West NA, Ouyang L et al. Corticosteroid Treatment and growth patterns in ambulatory males with Duchenne muscular dystrophy. J Pediatr 2016; 173: 207–213. doi: 10.1016/j.jpeds.2016.02.067.

21. Crabtree NJ, Adams JE, Padidela R et al. Growth, bone health & ambulatory status of boys with DMD treated with daily vs. intermittent oral glucocorticoid regimen. Bone 2018; 116: 181–186. doi: 10.1016/j.bone.2018.07.019.

22. Skoner DP, Rachelefsky GS, Meltzer EO et al. Detection of Growth suppression in children during treatment with intranasal beclomethasone dipropionate. Pediatrics 2000; 105 (2): e23–e23. doi: 10.1542/peds.105.2.e23.

23. Bodor M, McDonald CM. Why short stature is beneficial in duchenne muscular dystrophy. Muscle Nerve 2013; 48 (3): 336–342. doi: 10.1002/mus.23793.

24. Joseph S, Wang C, Di Marco M et al. Fractures and bone health monitoring in boys with Duchenne muscular dystrophy managed within the Scottish Muscle Network. Neuromuscul Disord 2019; 29 (1): 59–66. doi: 10.1016/j.nmd.2018.09.005.

25. Mayo AL, Craven BC, McAdam LC et al. Bone health in boys with Duchenne muscular dystrophy on long-term daily deflazacort therapy. Neuromuscul Disord 2012; 22 (12): 1040–1045. doi: 10.1016/j.nmd.2012.06.354.

26. Bothwell JE, Gordon KE, Dooley JM et al. Vertebral fractures in boys with Duchenne muscular dystrophy. Clin Pediatr 2016; 42 (4): 353–356. doi: 10.1177/000 992280304200408.

27. Goemans NM, Tulinius M, Van Der Akker JT et al. Systemic Administration of PRO051 in Duchenne‘s Muscular Dystrophy. N Engl J Med 2011; 364 (16): 1513–1522. doi: 10.1056/NEJMoa1011367.

28. Braat E, Hoste L, Liesbeth De Waele et al. Renal function in children and adolescents with Duchenne muscular dystrophy. Neuromuscul Disord 2015; 25 (5): 381–387. doi: 10.1016/j.nmd.2015.01.005.

29. Villa CR, Kaddourah A, Mathew J et al. Identifying evidence of cardio-renal syndrome in patients with Duchenne muscular dystrophy using cystatin C. Neuromuscul Disord 2016; 26 (10): 637–642. doi: 10.1016/j.nmd.2016.07.010.

30. Judd LL, Schettler PJ, Brown ES et al. Adverse consequences of glucocorticoid medication: psychological, cognitive, and behavioral effects. Am J Psychiatry 2014; 171 (10): 1045–1051. doi: 10.1176/appi.ajp.2014.13091264.