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Duchenne and Becker muscular dystrophy
A group of rare, genetic, progressive muscular dystrophies, including Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD) and a symptomatic form in female carriers. The diseases represent a spectrum of severity ranging from progressive skeletal and cardiac muscle wasting and weakness (DMD, BMD) to less severe muscle weakness or isolated cardiomyopathy affecting carrier females.
ORPHA:262Classification level: Group of disorders
- Severe dystrophinopathy, Duchenne and Becker type
- Prevalence: 1-9 / 100 000
- Inheritance: X-linked recessive
- Age of onset: Adolescent, Adult, Childhood
- ICD-10: -
- OMIM: -
- UMLS: C3542021
- MeSH: -
- GARD: -
- MedDRA: -
The prevalence of DMD ranges between 1/3,500-1/ 9,300 male births. The prevalence of BMD varies from 1/16,700 to 1/18,500 male births. The prevalence of symptomatic female carriers is unknown.
Dystrophinopathies present with a spectrum of severity whereby BMD is at the mildest end and DMD the most severe, there is an intermediate phenotype in between. At the mildest end of the spectrum exercise-induced muscle cramps and myoglobinuria may be the only feature while at the severe end, there may be complete loss of muscle function, cardiomyopathy and respiratory failure. DMD presents in early childhood, motor milestones are delayed. Brain involvement leads to cognitive impairment (affecting about a third of patients) and/or pervasive behavioral disorders such as ADHD (attention deficit hyperactivity disorder), autism, anxiety and obsessive compulsive disorder. Muscle hypertrophy is evident, especially in the calf muscles. Progression is rapid, such that by the age of 5 there is likely to be a waddling gait and positive Gowers' sign. In untreated boys, walking is lost by 13 years of age (mean 9.5 years). Following loss of ambulation, scoliosis, respiratory failure and cardiomyopathy develop. BMD presents a broad spectrum of clinical severity, with onset of symptoms occurring from early childhood to as late as the sixth decade. Manifesting carriers of DMD and BMD may present with varying degrees of cardiomyopathy and muscle weakness. X-linked dilated cardiomyopathy (XLDCM), which may be caused by mutations in the dystrophin gene, presents with very severe, rapidly progressive, dilated cardiomyopathy.
Dystrophinopathies are allelic conditions caused by deletions, duplications and mutations in the DMD gene, located on the X chromosome (Xp21.2). DMD genetic variants are frame-shift, while BMD variants are in-frame.
The clinical diagnosis can be confirmed by several methods. Creatine Kinase (CK) is very raised. Molecular genetic analysis by MLPA (multiplex ligation-dependent probe amplification) will show a deletion in 60%; full gene sequencing is necessary to identify small deletions, duplications and nonsense mutations. Muscle biopsy for dystrophin analysis which is absent in DMD and reduced in BMD.
The differential diagnosis includes LGMD and, in adults, other muscle disorders presenting with a raised CK.
Prenatal diagnosis requires the most precise molecular diagnosis possible in the index case.
The pattern of inheritance is X-linked recessive. Genetic counselling of affected families is recommended and screening of women carriers in the family is important.
Management and treatment
There is no known cure for this group of dystrophinopathies. In DMD, treatment with corticosteroids stabilizes motor function and delays loss of ambulation and respiratory failure by several years. Physiotherapy and orthotics delay the onset of joint contractures. Non-invasive ventilation (NIV) to treat respiratory failure prolongs life expectancy. Regular cardiac monitoring from diagnosis with early treatment using ACE (angiotensin-converting enzyme) inhibitors and beta blockers stabilizes cardiomyopathy. For XLDCM, cardiac transplantation is the treatment of choice.
Life expectancy is shortened by cardiac and respiratory involvement, but can be substantially improved with regular monitoring and pro-active management.
A summary on this disease is available in Deutsch (2007) Français (2007) Italiano (2007) Português (2007) Español (2020) Nederlands (2020) Greek (2007, pdf)
- Article for general public
- Deutsch (2014, pdf) - ACHSE
Disease review articles
- Clinical genetics review
- English (2018) - GeneReviews
- Guidance for genetic testing
- Français (2016, pdf) - ANPGM
: produced/endorsed by FSMR(s)