The Duchenne muscular dystrophy (DMD) Is a neuromuscular disease, characterized by the presence of significant muscle weakness, which develops in a generalized and progressive way (World Health Organization, 2012).
It is the most common type of muscular dystrophy in humans (López-Hernández, 2009) and affects 1 in 3,500 children worldwide (Duchenne Parent Project, 2012). The vast majority of the disease affects males in the early stages of life (World Health Organization, 2012).
There are different types of muscular dystrophy. Symptoms typically begin during childhood. Weakness and loss of muscle mass cause serious difficulties in acquiring or maintaining walking, breathing and / or swallowing (Mayo Clinic, 2013).
The neuromuscular effects offer a chronic prognosis. In most cases, people with Duchenne muscular dystrophy die in young adulthood due to the development of secondary pathologies such as heart failure or cardiomyopathies (World Health Organization, 2012).
What is Duchenne muscular dystrophy?
Duchenne muscular dystrophy is a disease that affects the individual through a weakness and Progressive muscle degeneration (Muscular Dystrophy Association, 2016).
Due to a genetic mutation, the absence of a particular protein in people with Duchenne muscular dystrophy will cause the loss of muscular functionality.
Generally, the symptoms are usually present in the lower extremities extending to the rest of areas.
How many people have Duchenne muscular dystrophy?
The World Health Organization (2012) notes that the incidence of Duchenne muscular dystrophy is estimated to be approximately 1 case per 3,300 inhabitants.
Specifically, some research shows that DMD affects 1 out of every 3,500 male live births (López-Hernández, 2009).
In the case of the US, it is not known with certainty how many people in all age ranges suffer from Duchenne muscular dystrophy. Some studies have estimated that one in every 5,600-7,770 adult males between 5 and 24 years of age present a diagnosis of Duchenne or Becker muscular dystrophy (Centers for Disease Control and Prevention, 2015).
What are the symptoms of Duchenne muscular dystrophy?
The most characteristic of the disorders that belong to the group of muscular dystrophies is the muscular weakness; However, depending on the type, specific symptoms may appear that will vary depending on the age of onset, the affected and fundamentally affected muscle groups (Mayo Clinic, 2013).
Normally, the development of Duchenne muscular dystrophy is quite predictable. Parents may observe some rather significant signs, such as difficulty or inability to learn to walk, abnormal increase in calf muscles ( Pseudohypertrophy ) (Duchenne Parent Project, 2012).
Some of the most characteristic symptoms and signs of Duchenne muscular dystrophy occurring early in a child's life are (Mayo Clinic, 2013):
- Recurrent falls.
- Difficulty or inability to stand up or adopt a specific posture.
- Difficulty or inability to walk, run or jump.
- Walk on the tip of the.
- Stiffness and / or muscle pain in large muscle groups.
- Learning difficulties .
Similarly, the association Duchenne Parent Project (2012) highlights the most common symptoms and clinical manifestations:
- Delay in the acquisition of language and speech.
- Difficulties and behavior problems.
- Learning difficulties.
- Muscular weakness.
- Contractures and stiffness in the articular areas.
- Pseudohypertrophy in the muscles of the calves.
- Lordosis .
- Weakness of heart and respiratory muscles.
What is the evolution of symptoms in Duchenne muscular dystrophy?
All muscle symptoms begin with weakness of the pelvic girdle muscles, twins, and various gait alterations that are significant before age 5 (López-Hernández, 2009).
At the preschool stage, children with Duchenne muscular dystrophy may fall frequently or have difficulty walking, climbing stairs and / or running (Duchenne Parent Project, 2012).
As the pathology progresses, at school age, it is quite likely that children will use only the toes to walk. We can observe a treadmill and insecure and that can cause numerous falls. They often employ some strategies to maintain their balance such as pushing the shoulders back or clinging to their own body (Duchenne Parent Project, 2012).
Around 9 years of age, most people are unable to walk, because of this they begin to develop numerous musculoskeletal deformities -coliosis, contractures, etc.- (López-Hernández, 2009).
In the adolescent stage, they will present significant difficulties to efficiently execute activities related to the use of the upper limbs, legs or trunk. At this stage they will require mechanical support and assistance (Duchenne Parent Project, 2012).
Degeneration and muscle weakness continue to progress until reaching the muscles responsible for respiratory and cardiac function (López-Hernández, 2009). Due to all this, the patient's survival is severely compromised, leading in most cases to death .
What is the cause of Duchenne muscular dystrophy?
Several genes have been identified that are involved in the production of proteins that are responsible for protecting against damage and injury to muscle fibers (Mayo Clinic, 2013).
Specifically, each type of muscular dystrophy occurs as a consequence of a particular genetic mutation. Some of these mutations are inherited; However, in most cases it occurs spontaneously during the gestation (Mayo Clinic, 2013).
In the case of Duchenne muscular dystrophy, the researchers identified a specific gene located in the X chromosome Which could present the mutation responsible for this pathology (Muscular Dystrophy Association, 2016).
Thus, in 1987, the protein associated with this gene was identified, Dystrophin . Thus, the lack or absence of this protein implies that the muscles are fragile and easily damaged (Muscular Dystrophy Association, 2016).
In addition, it has been possible to identify a recessive inheritance pattern linked to the X chromosome, being the mother carrier (Muscular Dystrophy Association, 2016). Due to this fact, this type of disease is more frequent in men than in women.
Men have an XY chromosome composition, while women have XX. Therefore, if an X chromosome has a mutation in the DMD gene, Duchenne muscular dystrophy will be present due to the lack of production of Dystrophin (National Human Genome Research Institute, 2013).
However, in the case of women who have two X chromosomes and therefore two copies of the DMD gene, if one of them is altered, the other will be able to continue producing dystrophin and thus maintain muscle neuroprotection (National Human Genome Research Institute, 2013).
How is Duchenne Muscular Dystrophy diagnosed?
In this type of pathologies different interventions can be performed to determine their diagnosis (National Human Genome Research Institute, 2013).
Clinical diagnosis can already be determined when a child begins to have progressive muscle weakness. At 5 years of age there are obvious symptoms. If early intervention is not performed, children will have functional dependence before the age of 13 (National Human Genome Research Institute, 2013).
Apart from the observation and clinical examination, some of the following techniques may be used to identify the presence of Duchenne muscular dystrophy (Mayo Clinic, 2013):
- Enzyme tests : Damaged muscles can release various enzymes, such as Creatine kinase (CK). The presence of abnormally high levels suggests the presence of some type of muscular pathology.
- Electomygraphy : Changes in electrical muscle patterns may suggest or confirm the condition of some muscle disease.
- Genetic studies : Are performed to detect possible genetic mutations that lead to the development of various types of muscular dystrophy.
- Muscle biopsy : Extracting small portions of muscle tissue are useful for detecting micro and macroscopic damage in muscle groups.
- Cardiac and respiratory tests : They are fundamental to detect the possible extension of muscle weakness and atrophy.
Is there treatment for Duchenne muscular dystrophy?
At present, a cure for Duchenne muscular dystrophy has not been identified (Duchenne Parent Project, 2012).
Despite this, various treatments have been used that have been shown to be effective both for the reduction of symptoms and for the improvement of quality of life Of people with this type of pathology (Duchenne Parent Project, 2012).
This disease, due to the clinical progression and the wide variety of symptoms, will require a multidisciplinary and comprehensive intervention performed by a wide variety of specialists: pediatrician, physiotherapist, neurologist, neuropsychologist, occupational therapist, speech therapist, nutritionist, endocrinologist, geneticist, cardiologist , Pulmonologist, orthopedist, rehabilitator and surgeon, among others (Duchenne Parent Project, 2012).
In many cases, specialists may recommend pharmacological interventions (Mayo Clinic, 2013):
- Corticosteroids : Some of the drugs in this group can improve muscle strength and control the progression of muscle degeneration (Mayo Clinic, 2013). However, repeated use of these drugs can cause side effects such as weight gain or bone weakness (Mayo Clinic, 2013).
- Cardiac Drugs : Angiotensin inhibitors or beta-blockers may be beneficial when muscular dystrophy has reached the cardiac muscle groups (Mayo Clinic, 2013).
Not only drugs are useful for intervention in Duchenne muscular dystrophy, there are both therapeutic interventions and methods of care that can improve the quality of life of these people (Mayo Clinic, 2013).
Some beneficial interventions are (Duchenne Parent Project, 2012):
- Stretching exercises and muscle movement.
- Aerobic and strengthening exercise.
- Methods of mobility: walking sticks, walkers, wheelchairs, etc.
- Orthopedic methods: night, long leg or hand splints.
- Respiratory care: artificial respiration, non-invasive ventilation, assisted cough, etc.
What is life expectancy for people with Duchenne muscular dystrophy?
Until relatively few years ago, people with Duchenne muscular dystrophy did not survive much longer after reaching adolescence (Muscular Dystrophy Association, 2016).
The great advances in medical, technical and genetic research have succeeded both in curbing the progression of the disease and in granting a considerable increase in the quality of life to the individuals who suffer it (Muscular Dystrophy Association, 2016). Thus, cardiac and respiratory care is critical for the preservation of vital functions (Muscular Distrophy Association, 2016).
In many cases, they are able to reach the post-teen stages. More and more cases of Duchenne muscular dystrophy are described in adults up to 30 years of age, including people who survive to age 40 and 50 (Muscular Dystrophy Associatin, 2016).
What is the current status of research on Duchenne muscular dystrophy?
Clinical trials and trials are currently oriented towards the development of gene therapies that modify mutations and deficiencies in the production of Dystrophin (Muscular Dystrophy Association, 2016).
Some of the mechanisms most investigated are (López-Hernández, 2009):
- Replacement of damaged gene.
- Modification of the endogenous gene (exonic omission therapy and omission of stop codons).
- Overexpression / inhibition of phenotype modifiers.
CONCLUSIONS
Duchenne muscular dystrophy is a disease that causes a significant disability in both children and young adults and presents a devastating prognosis.
Although the clinical and experimental investigations have made important advances in the treatment of symptoms, there is still no cure for this type of pathologies.
It is essential to gain a deep understanding of the biological and genetic basis for finding a curative treatment for Duchenne muscular dystrophy.
Bibliography
- CDC. (2016). Centers for Disease Control and Prevention . Retrieved from Muscular Dystrophy: http://www.cdc.gov/ncbddd/musculardystrophy/data.html.
- DPP. (2016). What is Duchenne? Retrieved from the Duchene Parent Project Association Spain: https://www.duchenne-spain.org/.
- López-Hernández, L. B., Vázquez-Cárdenas, N.A., & Luna-Padrón, E. (2009). Duchenne muscular dystrophy: current and prospects of treatment. Rev Neurol , 49 (7), 369-375.
- Mayo Clinic. (2014). Diseases and Conditions: Muscular dystrophy . Retrieved from the May Clinic: http://www.mayoclinic.org/diseases-conditions/.
- MDA. (2016). Duchenne Muscular Dystrophy (DMD) . Retrieved from the Muscular Dystrophy Association: https://www.mda.org/disease/.
- NHI. (2013). Learning About Duchenne Muscular Dystrophy . Retrieved from the National Human Genome Research Institute: https://www.genome.gov/19518854.
- WHO. (2012). United to fight rare diseases . Obtained from World Health Organization: http://www.who.int/bulletin/volumes/.
- Image source.