Functional performance and muscular strength in symptomatic female carriers of Duchenne muscular dystrophy

Abstract

Duchenne muscular dystrophy (DMD) usually affects men. However, women are also affected in rare instances. Approximately 8% of female DMD carriers have muscle weakness and cardiomyopathy. The early identification of functional and motor impairments can support clinical decision making. Objective: To investigate the motor and functional impairments of 10 female patients with dystrophinopathy diagnosed with clinical, pathological, genetic and immunohistochemical studies. Methods: A descriptive study of a sample of symptomatic female carriers of DMD mutations. The studied variables were muscular strength and functional performance. Results: The prevalence was 10/118 (8.4%) symptomatic female carriers. Deletions were found in seven patients. The age of onset of symptoms in female carriers of DMD was quite variable. Pseudohypertrophy of calf muscles, muscular weakness, compensatory movements and longer timed performance on functional tasks were observed in most of the cases. Differently from males with DMD, seven female patients showed asymmetrical muscular weakness. The asymmetric presentation of muscle weakness was frequent and affected posture and functionality in some cases. The functional performance presents greater number of compensatory movements. Time of execution of activities was not a good biomarker of functionality for this population, because it does not change in the same proportion as the number of movement compensations. Conclusion: Clinical manifestation of asymmetrical muscle weakness and compensatory movements, or both can be found in female carriers of DMD mutations, which can adversely affect posture and functional performance of these patients.

Resumo

A distrofia muscular de Duchenne (DMD) geralmente afeta indivíduos do sexo masculino. No entanto, mulheres também são acometidas em casos raros. Aproximadamente 8% das portadoras de DMD têm fraqueza muscular ou cardiomiopatia. A identificação precoce das alterações funcionais e motoras pode alterar a tomada de decisão clínica. Objetivo: Investigar as deficiências motoras e funcionais de 10 pacientes do sexo feminino com distrofinopatia diagnosticada por estudos clínicos, patológicos, genéticos e imuno-histoquímicos. Método: Estudo descritivo de uma amostra de portadoras sintomáticas de mutações DMD. As variáveis estudadas foram força muscular e desempenho funcional. Resultados: A prevalência foi de 10/118 (8,4%) de portadoras sintomáticas de DMD. Foram encontradas deleções em sete pacientes. A idade de início dos sintomas em portadoras de DMD foi variável. Pseudo-hipertrofia de panturrilhas, movimentos compensatórios, fraqueza muscular e aumento no tempo de execução de tarefas funcionais foram observados na maioria dos casos. Diferentemente dos homens com DMD, sete pacientes apresentaram fraqueza muscular assimétrica. A apresentação assimétrica da fraqueza muscular foi frequente, podendo afetar a postura e a funcionalidade. O desempenho funcional geralmente apresenta aumento no número de movimentos compensatórios. Não podemos sempre considerar o tempo como um bom marcador de funcionalidade para essa população, uma vez que não muda na mesma proporção que o número de compensações em todas essas pacientes. Conclusão: Fraqueza muscular assimétrica e movimentos compensatórios, ou ambos, podem ser encontrados em portadoras sintomáticas de DMD, o que pode afetar a postura e a funcionalidade dessas pacientes.

Keywords:

Duchenne muscular dystrophy - motor activity - muscle strength - female

Palavras-chave:

distrofia muscular de Duchenne - atividade motora - força muscular - feminino

• References

• 1 Moser H, Emery AE. The manifesting carrier in Duchenne muscular dystrophy. Clin Genet. 1974;5(4):271-84. https://doi.org/10.1111/j.1399-0004.1974.tb01694.x
• 2 Norman A, Harper P. A survey of manifesting carriers of Duchenne and Becker muscular dystrophy in Wales. Clin Genet. 1989 Jul;36(1):31-7. https://doi.org/10.1111/j.1399-0004.1989.tb03363.x
• 3 Kamakura K, Kawai M, Arahata K, Koizumi H, Watanabe K, Sugita H. A manifesting carrier of Duchenne muscular dystrophy with severe myocardial symptoms. J Neurol. 1990 Dec;237(8):483-5. https://doi.org/10.1007/bf00314767
• 4 Hoogerwaard EM, van der Wouw PA, Wilde AA, Bakker E, Ippel PF, Oosterwijk JC, et al. Cardiac involvement in carriers of Duchenne and Becker muscular dystrophy. Neuromuscul Disord. 1999 Jul;9(5):347-51. https://doi.org/10.1016/s0960-8966(99)00018-8
• 5 Sussman M. Duchenne muscular dystrophy. J Am Acad Orthop Surg. 2002 Mar-Apr;10(2):138-51.https://doi.org/10.5435/00124635-200203000-00009
• 6 Adachi K, Hashiguchi S, Saito M, Kashiwagi S, Miyazaki T, Kawai H, et al. Detection and management of cardiomyopathy in female dystrophinopathy carriers. J Neurol Sci. 2018 Mar;386:74-80. https://doi.org/10.1016/j.jns.2017.12.024
• 7 Hoogerwaard EM, Bakker E, Ippel PF, Oosterwijk JC, Majoor-Krakauer DF, Leschot NJ, et al. Signs and symptoms of Duchenne muscular dystrophy and Becker muscular dystrophy among carriers in The Netherlands: a cohort study. Lancet. 1999 Jun;353(9170):2116-9.https://doi.org/10.1016/s0140-6736(98)10028-4
• 8 Soltanzadeh P, Friez MJ, Dunn D, von Niederhausern A, Gurvich OL, Swoboda KJ, et al. Clinical and genetic characterization of manifesting carriers of DMD mutations. Neuromuscul Disord. 2010 Aug;20(8):499-504. https://doi.org/10.1016/j.nmd.2010.05.010
• 9 Werneck LC, Lemos SML, Magdalena N. Distrofia muscular de Duchenne em menina com translocação cromossômica. Arq Neuropsiquiatr. 1988;46(4):401-405. http://dx.doi.org/10.1590/S0004-282X1988000400012
• 10 Cotta A, Paim JF, Carvalho E, Navarro MM, Valicek J, da-Cunha-Junior AL, et al. Phenotypic Variability of Dystrophinopathy Symptomatic Female Carriers. Can J Neurol Sci. 2017 May;44(3):304-10. https://doi.org/10.1017/cjn.2016.448
• 11 Hukuda ME, Escorcio R, Fernandes LA, de Carvalho EV, Caromano FA. Evaluation scale development, reliability for sitting and standing from the chair for Duchenne muscular dystrophy. J Mot Behav. 2013;45(2):117-26. https://doi.org/10.1080/00222895.2012.760513
• 12 Escorcio R, Caromano FA, Hukuda ME, Fernandes LA. Development of an evaluation scale for sitting and standing from the ground for children with Duchenne muscular dystrophy. J Mot Behav. 2011;43(1):31-6. https://doi.org/10.1080/00222895.2010.530306
• 13 Fernandes LA, Caromano FA, Hukuda ME, Escorcio R, Carvalho EV. Elaboration and reliability of functional evaluation on going up and downstairs scale for Duchenne Muscular Dystrophy. Rev Bras Fisioter. 2010 Nov/Dec;14(6):518-26. http://dx.doi.org/10.1590/S1413-35552010000600011
• 14 de Carvalho EV, Hukuda ME, Escorcio R, Voos MC, Caromano FA. Development and Reliability of the Functional Evaluation Scale for Duchenne Muscular Dystrophy, Gait Domain: A Pilot Study. Physiother Res Int. 2015 Sep;20(3):135-46. https://doi.org/10.1002/pri.1605
• 15 Song TJ, Lee KA, Kang SW, Cho H, Choi YC. Three cases of manifesting female carriers in patients with Duchenne muscular dystrophy. Yonsei Med J 2011 Jan;52(1):192-5. https://doi.org/10.3349/ymj.2011.52.1.192
• 16 Brioschi S, Gualandi F, Scotton C, Armaroli A, Bovolenta M, Falzarano MS, et al. Genetic characterization in symptomatic female DMD carriers: lack of relationship between X-inactivation, transcriptional DMD allele balancing and phenotype. BMC Med Genet. 2012 Aug;13:73. https://doi.org/10.1186/1471-2350-13-73
• 17 Grain L, Cortina-Borja M, Forfar C, Hilton-Jones D, Hopkin J, Burch M. Cardiac abnormalities and skeletal muscle weakness in carriers of Duchenne and Becker muscular dystrophies and controls. Neuromuscul Disord. 2001 Mar;11(2):186-91. https://doi.org/10.1016/s0960-8966(00)00185-1
• 18 Oliveira ASB, Gabbai AA, Schmidt B, Kiyomoto BH, Lima JGC, Minetti C, et al. Carrier detection of Duchenne and Becker muscular dystrophy using muscle dystrophin immunohistochemistry. Arq Neuropsiquiatr. 1992 Dec;50(4):478-85. http://dx.doi.org/10.1590/S0004-282X1992000400010
• 19 Martini J, Voos MC, Hukuda ME, Resende MB, Caromano FA. Compensatory movements during functional activities in ambulatory children with Duchenne muscular dystrophy. Arq Neuropsiquiatr. 2014 Jan;72(1):5-11. https://doi.org/10.1590/0004-282X20130196
• 20 Mercier S, Toutain A, Toussaint A, Raynaud M, de Barace C, Marcorelles P, et al. Genetic and clinical specificity of 26 symptomatic carriers for dystrophinopathies at pediatric age. Eur J Hum Genet. 2013 Aug;21(8):855-63. https://doi.org/10.1038/ejhg.2012.269
• 21 Juan-Mateu J, Rodríguez MJ, Nascimento A, Jiménez-Mallebrera C, González-Quereda L, Rivas E, et al. Prognostic value of X-chromosome inactivation in symptomatic female carriers of dystrophinopathy. Orphanet J Rare Dis. 2012;7(1):82. https://doi.org/10.1186/1750-1172-7-82