Duchenne Muscular Dystrophy

This disease gets its name from the protein dystrophin, which due to mutation of its on the genetic material (DNA) is not produced or produced in an functional way. The disease affects mainly boys, 1: 3,500 births worldwide every year due to the way it is inherited and symptoms can be evident from the ages of 3-5 years or even earlier. Girls are carriers of the mutant gene, usually do not get sick (they may have muscle weakness and fatigue), unless their father and their mother are both carriers, which is extremely rare.

This disease primarily affects the skeletal muscles that control the movement of the human body and the heart muscle. Progressively, the muscles of pelvis and legs are affected and atrophied, followed by the muscles of the limbs, the throat and progressively many others.

The first symptoms that can be observed are:

  • Impotence – frequent falls,
  • Difficulty in running,
  • Difficulty of climbing stairs,
  • Difficulty in lifting off the ground (Gower point, where the knees touch the knees in order to get up) or from a chair,
  • Development of large tibia,
  • Gradual occurrence of the walking feature on toes,
  • Delayed speech initiation,
  • Behavioral or learning difficulties.

By the age of 8-14 years, a wheelchair may be needed due to the loss of walking ability. In addition, scoliosis develops due to weak body posture. In the middle of puberty, symptoms of cardiomyopathy are manifested, and at the age of 20, respiratory problems may begin as the intervertebral muscles and the diaphragm are affected by the disease. Endocrine issues might manifest. 

How can I be sure of the diagnosis?

  • The child has muscular weakness and large legs, which are identified by appropriate clinical examination.
  • Genetic diagnosis demonstrates the type of mutation in the dystrophin gene and is confirmed by the biopsy of the muscle, where its lack of muscle cells appears.
  • In biochemical blood tests CK enzyme is very high, which proves damage in muscle cells.

What happens after diagnosis?

The child’s therapeutic management is conducted by a group of specialized professionals, a multidisciplinary team.

  • Physiotherapy begins with everyday exercises and not difficult by the child itself and with the parents’ help. Later, supportive devices are used, which contribute to the correct posture of the body. Watch playlist  with physio exercises in MDA’s youtube channel: https://www.youtube.com/playlist?list=PLgQ8ZEc-HmV80WwkVNtNnuzwTywmgxN-E
  • The heart is monitored with the necessary examinations every year or more often and of course there is a close monitoring from every specialty of the multidisciplinary team.
  • At an appropriate age, corticoids are taken to help maintain upper and lower limb movement and maintain proper musculoskeletal function as well as proper respiratory function.
  • Every child should be monitored by a nutritionist, especially after taking the corticosteroids, for weight control, and in order to properly obtain the necessary nutrients.
  • Psychological support for children and parents is required, as well as communication and contact with people with similar concerns, with the aim of exchanging experiences, agonies and mutual support.
  • There should be contact with organizations that deal with and safeguard patients’ rights and seek to find new, safe and more effective pharmaceutical approaches.

Information about clinical trials conducted globally: https://www.centerwatch.com/clinical-trials/listings/condition/350/muscular-dystrophy/ and https://clinicaltrials.gov/ct2/home

For more details on patient care, consult the “Standards of Care” and the latest articles related to them (23/1/2018):

  1. Birnkrant D.J., Bushby K. et al., Diagnosis and Management of Duchenne Muscular Dystrophy, Part 1: Diagnosis, and Neurosurgery, Rehabilitation, Endocrine, and Gastrointestinal and Nutritional Management, The Lancet, 2018.
  2. Birnkrant D.J., Bushby K. et al., Diagnosis and management of Duchenne muscular dystrophy, Part 2: respiratory, cardiac, bone health, and orthopedic management, The Lancet, 2018.
  3. Birnkrant D.J., Bushby K. et al., Diagnosis and Management of Duchenne Muscular Dystrophy, Part 3: primary, emergency management, psychosocial care, and transitions of care over the lifespan, The Lancet, 2018.

Family Guide :  MDA DMD Family Guide

Duchenne Standards of Care Videos, by World Duchenne Organization: https://www.youtube.com/watch?v=YFS8x59mrco&list=PLi4jXxW5UG9gZRGSJMwrTrUahC4U8Xj62&ab_channel=WorldDuchenneOrganization  

Updated information on nutrition:  https://drive.google.com/file/d/1hvT_w19poEjQEqhyFBa42wrHbJPqmTQl/view?u…

References

  • AM. Connolly et al, Outcome Reliability in Non Ambulatory Boys/Men with Duchenne Muscular Dystrophy, Muscle Nerve., 2015, 51, 4, pp. 522–532.
  • AR. Punnoose, et al, Cardiac disease burden and risk of mortality in hospitalized muscular dystrophy patients, Pediatr.Cardiol., 2016, 37, 7, pp. 1290-1296.
  • B. Bartels et al, Cardiopulmonary exercise testing in children and adolescents with dystrophinopathies: a pilot study, Pediatr. Phys. Ther., 2015, pp. 227-234.
  • C.L. Wood et al, Short stature and pubertal delay in Duchenne muscular Dystrophy, Arch. Dis. Child, 2016, 101, pp.101-106.
  • CM. McDonald et al, THE 6-MINUTE WALK TEST AND OTHER ENDPOINTS IN DUCHENNE MUSCULAR DYSTROPHY: LONGITUDINAL NATURAL HISTORY OBSERVATIONS OVER 48 WEEKS FROM A MULTICENTER STUDY, 2013, Wiley Online Library.
  • D. Ombrone et al, Expanded newborn screening by mass spectrometry: new tests, future perspectives, Mass Spectro. Rev., 2016, 35, pp. 71-84.
  • E. Matthews et al, Corticosteroids for the treatment of Duchenne muscular dystrophy. Cochrane Database of Systematic Reviews, 2016, 5.
  • G. Schram et al, All-Cause Mortality and Cardiovascular Outcomes With Prophylactic Steroid Therapy in Duchenne Muscular Dystrophy, , Journal of the American College of Cardiology, 61, 9, 2013.
  • H.J.A. Van Ruiten, V. Straub, K. Bushby, M. Guglieri, Improving recognition of Duchenne muscular dystrophy: a retrospective case note review, Arch. Dis. Child., 2014, 99, pp. 1074-1077.
  • J. Chung et al, Twenty-year follow up of newborn screening for patients with muscular dystrophy, Muscle Nerve, 2016, 53, 4, pp. 570-578.
  • JG. Hendriksen et al, Diagnosis and treatment of obsessive compulsive behavior in a boy with Duchenne muscular dystrophy and autism spectrum disorder: a case report. Neuromuscul. Disord., 2016, 26, 10, pp. 659-661.
  • J. Rahbek, B.F. Steffensen, K. Bushby, I.J.M. De Groot, 206th ENMC iinternational workshop: Care for a novel group of patients-adults with Duchenne muscular dystrophy, Naarden, The Netherlands, 23-25 May 2014, Neuromuscular Disord., 2015, 25, pp. 727-738.
  • K. Bushby et al, Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and phychosocial management, Lancet Neurol., 2010, 9, pp. 77-93.
  • K. Caspers Conway et al, Neurobehavioral concerns among males in dystrophinopathy using population-based surveillance data from the muscular dystrophy surveillance, tracking, and research network, J. Dev., Behav. Pediatr., 2015, 36, 6, pp. 456-463.
  • T. Mirski, T.O. Crawford, Motor and cognitive delay in Duchenne muscular dystrophy: Implication for early diagnosis, J. Pediatr., 2014, 165, pp. 1008-1010.
  • L. Friedman Ross, Ethical and policy issues in newborn screening of children for neurologic and developmental disorders, Pediatr. Clin. N. Am., 2015, 62, pp. 787-798.
  • M. Jansen , N. Van Alfen, A.C.H. Geurts, I.J.M. De Groot, Assisted bicycle training delays functional deterioration in boys with Duchenne muscular dystrophy: the randomized controlled trial “no use is disuse”, Neurorehabil. Neural Repair, 2013, 27, 9, pp. 816-827.
  • M. Jansen et al, The assisted 6-minute cycling test to assess endurance in children with a neuromuscular disorder, Muscle Nerve, 2012, 46, pp. 520-530.
  • M. Pane et al, Attention deficit hyperactivity disorder and cognitive function in Duchenne muscular dystrophy: phenotype – genotype correlation. J. Pediatr., 2012, 161, pp. 705-709.
  • M. Pane et al, Benefits of glucocorticoids in non-ambulant boys/men with Duchenne muscular dystrophy: A multicentric longitudinal study using the Performance of Upper Limb test, Neurological Sciences, 2015, 25, 10, pp. 749-753.
  • Muscular Dystrophy Canada, Duchenne Muscular Dystrophy, http://www.muscle.ca/about-muscular-dystrophy/types-of-neuromuscular-disorders/duchenne-muscular-dystrophy/, August 30, 2017.
  • Muscular Dystrophy Canada, Duchenne Muscular Dystrophy. http://muscle.ca/wp-content/uploads/2012/11/434E_Duchenne_MD_2007.pdf
  • Muscular Dystrophy Association, About Neuromuscular Diseases, June 08, 2017, https://www.mda.org/disease/
  • M. Winterholler et al, Stroke in Duchenne muscular dystrophy, a retrospective study in 54 patients, Stroke, 2016, 47, pp. 2123-2126.
  • N. Goemans, G. Buyse, Current treatment and management of dystrophinopathies, Curr. Treat. Opinions Neurol., 2014, 16, pp. 286-299.
  • NORD (National Organization for Rare Disorders), Rare Diseases,  https://rarediseases.org/rare-diseases/
  • N. Perera, H. Sampaio, H.Woodhead, M. Farrar, Fracture in Duchenne Muscular Dystrophy: Natural history and vitamin C deficiency, J. Child Neurol., 2016, 31, 9, pp. 1181-1187.
  • N. Tsakadze, L.W. Katzin, S. Krishnana, R.Behrouz, Cerebral infraction in Duchenne muscular dystrophy, J. Stroke Cerebrovasc., 2011, 20, 3, pp. 264-265.
  • P. Colombo  et al, Assessing mental health in boys with Duchenne muscular dystrophy: Emotional, behavioural and neurodevelopmental profile in an Italian clinical sample, Eur. J. Paediatr. Neurol., 2017, 21, 4, pp. 639-647.
  • R. Banihani et al, Cognitive and neurobehavioral profile in boys with Duchenne muscular dystrophy, J. Child Neurol., 2015, 30, 11, pp. 1472-1482.
  • S. Abbs et al, Best Practice Guidelines on molecular diagnostics in Duchenne/Becker muscular dystrophies, Neuromuscular Disorders, 2010, 20, pp. 422–427.
  • S. Buddhe, et al, Comparison of left ventricular function assessment between echocardiography and MRI in Duchenne muscular dystrophy, Pediatr. Radiol., 2016, 46, 10, pp. 1399-1408.
  • S.H. Wong et al, A mixed methods study of age at diagnosis and diagnostic odyssey for Duchenne muscular dystrophy, Eur. J. Hum. Genet., 2015, 23, pp. 1294-1300.
  • Vision – DMD, http://www.uppmd.org/projects/vision-dmd/
  • V. Ricotti  et al, Neurodevelpomental, emotional, and behavioural problems in Duchenne muscular dystrophy gene mutations, Dev. Med. Child Neurol., 2016, 58, pp. 77-84.
  • E. Mercuri, C.G. Bonnemann, F. Muntoni, Muscular Dystrophies, The Lancet 2019.
  • C. Hind et al, Aquatic therapy for boys with Duchenne muscular dystrophy (DMD): an external pilot randomised controlled trial, Pilot Feasibility Stud., 2017, 3:16.
  • HNishizawa et al,The effect of wearing nightsplintsfor one year on the standing motor function of patients with Duchenne muscular dystrophy,  Phys. Ther. Sci., 2018, 30: 4, pp. 576-579.
  • MToussaintet al,  Dysphagia in Duchenne muscular dystrophy: practical recommendations to guide management,  Rehabil., 2016, 38:20, pp. 2052-62.
  • DBrumbaugh et al, Nutritional and Gastrointestinal Management of the Patient With Duchenne Muscular Dystrophy, Pediatrics, 2018, 142: S53-S61.
  • KKikuchi et al, Approaches to Cough Peak Flow Measurement With Duchenne Muscular Dystrophy,  Care, 2018, 63: 12, pp.1514 -1519.
  • SD. Apkon  et al, Orthopedic and surgical management of the patient with Duchenne Muscular Dystrophy, Pediatrics, 2018, S82-S89.
  • M.Thangarajh  et al, Relationships between DMDmutations and neurodevelopment in dystrophinopathy , 2019, 22; 93 (17): e1597-e1604.
  • MThangarajh et al, Neurodevelopmental Needs in Young Boys with Duchenne Muscular Dystrophy (DMD): Observations from the Cooperative International Neuromuscular Research Group (CINRG) DMD Natural History Study (DNHS), PLoS Curr., 2018 17; 10.
  • LParisi et al,  Autism spectrum disorders in children affected by Duchenne muscular dystrophy. Minerva Pediatr., 2018, 70 (3): pp. 233-239.
  • HFujino et al, Autism spectrum disorders are prevalent among patients with dystrophinopathies., Neurol Sci., 2018, 39 (7): pp. 1279-1282.
  • Doorenweerd NMahfouz Avan Putten MKaliyaperumal RT’ Hoen PACHendriksen JGMAartsma-Rus AMVerschuuren JJGMNiks EHReinders MJTKan HELelieveldt BPF, Timing and localization of human dystrophin isoform expression provide insights into the cognitive phenotype of Duchenne muscular dystrophy, Sci Rep., 2017, 7 (1): pp. 12575.
  • P. Colombo et al , Assessing mental health in boys with Duchenne muscular dystrophy: Emotional, behavioural and neurodevelopmental profile in an Italian clinical sample. J. Paediatr. Neurol., 2017, 21 (4): pp. 639-647.
  • JGHendriksenet al, Diagnosis and treatment of obsessive compulsive behavior in a boy with Duchenne muscular dystrophy and autism spectrum disorder: A case report., Neuromuscul Disord., 2016, 26 (10): pp. 659-661.
  • VRicotti et al,  Neurodevelopmental, emotional, and behavioural problems in Duchenne muscular dystrophy in relation to underlying dystrophin gene mutations.,  Child Neurol., 2016, 58 (1): pp. 77-84.
  • RBanihani et al, Cognitive and Neurobehavioral Profile in Boys With Duchenne Muscular Dystrophy. Child Neurol., 2015, 30 (11): pp. 1472-82.
  • JGHendriksenJ.SVles, Neuropsychiatric disorders in males with Duchenne muscular dystrophy: frequency rate of attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder, and obsessive–compulsive disorder., Child Neurol.2008, 23(5): pp. 477-481.
  • JYWuK.CKubanEAllredFShapiroB.TDarras, Association of Duchenne muscular dystrophy with autism spectrum disorder, Child Neurol., 2005, 20 (10): pp. 790-795.

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