Does Motor Function Differ According to the Site of Mutation in Duchenne Muscular Dystrophy?

Abstract

Objectives

This study aimed to investigate whether the site of DMD gene mutations is linked to motor functions in children with Duchenne muscular dystrophy (DMD).

Methods

A total of 58 children with DMD, aged between 7 and 16 years, were divided into two groups according to the site of mutation (proximal or distal). Motor functions of the groups were compared.

Result

The physical and demographic characteristics of two groups were similar (p > 0.05). Distal group had significantly worser Brooke Lower Extremity Functional Classification (BLEFC) (median 3) and D2 score of Motor Function Measure (MFM-32/D2) (mean 86.78 ± 19.83) than proximal group [BLEFC, median 1; MFM-32/D2, mean 93.77 ± 14.89] (p ≤ 0.05). There was no difference in timed performance tests and Four Square Step Test between two groups (p > 0.05).

Conclusion

Considering that mutations in the distal site of the DMD gene may lead to poorer motor function, performance outcomes, dynamic balance and functional status compared to proximal mutations, it is important to take the mutation site into account in the evaluation and intervention of children with DMD. Early recognition of the mutation site may help professionals implement timely and proactive strategies to maintain motor functional abilities for a longer duration.

Keywords

Duchenne muscular dystrophy - DMD gene - dystrophin isoforms - motor functions - physical therapy - rehabilitation

Clinical Trial Registration

NCT05661071.

Publication History

Received: 26 October 2024

Accepted: 26 September 2025

Accepted Manuscript online:
06 October 2025

Article published online:
16 October 2025

• References

• 1 Aartsma-Rus A, Van Deutekom JC, Fokkema IF, Van Ommen GJB, Den Dunnen JT. Entries in the Leiden Duchenne muscular dystrophy mutation database: an overview of mutation types and paradoxical cases that confirm the reading-frame rule. Muscle Nerve 2006; 34 (02) 135-144
• 2 Salari N, Fatahi B, Valipour E. et al. Global prevalence of Duchenne and Becker muscular dystrophy: a systematic review and meta-analysis. J Orthop Surg Res 2022; 17 (01) 96
• 3 Blake DJ, Weir A, Newey SE, Davies KE. Function and genetics of dystrophin and dystrophin-related proteins in muscle. Physiol Rev 2002; 82 (02) 291-329
• 4 Muntoni F, Torelli S, Ferlini A. Dystrophin and mutations: one gene, several proteins, multiple phenotypes. Lancet Neurol 2003; 2 (12) 731-740
• 5 Venugopal V, Pavlakis S. Duchenne muscular dystrophy. StatPearls. 2023. Accessed 21 December 2023 at: https://www.statpearls.com/point-of-care/20747
• 6 Suthar R, Sankhyan N. Duchenne muscular dystrophy: a practice update. Indian J Pediatr 2018; 85 (04) 276-281
• 7 Bushby K, Finkel R, Birnkrant DJ. et al; DMD Care Considerations Working Group. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol 2010; 9 (01) 77-93
• 8 Desguerre I, Christov C, Mayer M. et al. Clinical heterogeneity of Duchenne muscular dystrophy (DMD): definition of sub-phenotypes and predictive criteria by long-term follow-up. PLoS One 2009; 4 (02) e4347
• 9 Ortiz-Corredor F, Sandoval-Salcedo A, Castellar-Leones S, Soto-Pena D, Ruíz-Ospina E, Suarez-Obando F. Trajectories of motor function in children with Duchenne muscular dystrophy: a longitudinal study on a Colombian population. Eur J Paediatr Neurol 2023; 47: 105-109
• 10 Thangarajh M, McDermott MP, Guglieri M, Griggs RC. Association between neurodevelopmental impairments and motor function in Duchenne muscular dystrophy. Ann Clin Transl Neurol 2023; 10 (12) 2285-2296
• 11 Birnkrant DJ, Bushby K, Bann CM. et al; DMD Care Considerations Working Group. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol 2018; 17 (03) 251-267
• 12 Case LE, Apkon SD, Eagle M. et al. Rehabilitation management of the patient with Duchenne muscular dystrophy. Pediatrics 2018; 142 (Suppl. 02) S17-S33
• 13 Coratti G, Lenkowicz J, Norcia G. et al; Italian DMD study group. Age, corticosteroid treatment and site of mutations affect motor functional changes in young boys with Duchenne muscular dystrophy. PLoS One 2022; 17 (07) e0271681
• 14 Matthews E, Brassington R, Kuntzer T, Jichi F, Manzur AY. Corticosteroids for the treatment of Duchenne muscular dystrophy. Cochrane Database Syst Rev 2016; 2016 (05) CD003725
• 15 Zamani G, Hosseinpour S, Ashrafi MR. et al. Characteristics of disease progression and genetic correlation in ambulatory Iranian boys with Duchenne muscular dystrophy. BMC Neurol 2022; 22 (01) 162
• 16 Wijekoon N, Gonawala L, Ratnayake P. et al. Duchenne muscular dystrophy from brain to muscle: the role of brain dystrophin isoforms in motor functions. J Clin Med 2023; 12 (17) 5637
• 17 Chesshyre M, Ridout D, Hashimoto Y. et al. Investigating the role of dystrophin isoform deficiency in motor function in Duchenne muscular dystrophy. J Cachexia Sarcopenia Muscle 2022; 13 (02) 1360-1372
• 18 Preethish-Kumar V, Shah A, Polavarapu K. et al. Disrupted structural connectome and neurocognitive functions in Duchenne muscular dystrophy: classifying and subtyping based on Dp140 dystrophin isoform. J Neurol 2022; 269 (04) 2113-2125
• 19 Brooke MH, Griggs RC, Mendell JR, Fenichel GM, Shumate JB, Pellegrino RJ. Clinical trial in Duchenne dystrophy. I. The design of the protocol. Muscle Nerve 1981; 4 (03) 186-197
• 20 Bérard C, Payan C, Hodgkinson I, Fermanian J. MFM Collaborative Study Group. A motor function measure for neuromuscular diseases. Construction and validation study. Neuromuscul Disord 2005; 15 (07) 463-470
• 21 İnal HS, Tarakçı E, Tarakçı D. et al. Turkish version of the motor function measure scale (MFM-32) forneuromuscular diseases: a cross-cultural adaptation, reliability, and validity study. Turk J Med Sci 2017; 47 (06) 1826-1833
• 22 Dite W, Temple VA. A clinical test of stepping and change of direction to identify multiple falling older adults. Arch Phys Med Rehabil 2002; 83 (11) 1566-1571
• 23 Aldirmaz E, Uğur F, Yilmaz Ö, Karaduman A, Alemdaroğlu-Gürbüz İ. A new instrument to assess dynamic balance in children with Duchenne muscular dystrophy: four square step test and its validity, reliability, and feasibility. Dev Neurorehabil 2023; 26 (01) 27-36
• 24 McDonald CM, Henricson EK, Han JJ. et al. The 6-minute walk test as a new outcome measure in Duchenne muscular dystrophy. Muscle Nerve 2010; 41 (04) 500-510
• 25 Brogna C, Coratt G, Pane M. et al; On behalf of the International DMD group. Correction: long-term natural history data in Duchenne muscular dystrophy ambulant patients with mutations amenable to skip exons 44, 45, 51 and 53. PLoS One 2019; 14 (07) e0220714
• 26 Hafner P, Schmidt S, Schädelin S. et al; MFM registry Study Group. Implementation of motor function measure score percentile curves - predicting motor function loss in Duchenne muscular dystrophy. Eur J Paediatr Neurol 2022; 36: 78-83