Becker's muscular dystrophy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Moises Romo, M.D.
Overview
Former "pseudohypertrophic muscular dystrophy", now Becker's muscular dystrophy, is a genetic neuromuscular condition characterized by slowly progresive weakness and atrophy of skeletal (mostly legs and pelvis) and cardiac muscles.
Historical Perspective
- Becker's muscular dystrophy was first described by Peter Emil Becker, a German neurologist, psychiatrist and geneticist, in 1953 with his thesis called ‘‘Dystrophia Musculorum Progessiva: A Genetic and Clinical Investigation of the Muscular Dystrophies’’, after his work was interrumpted in 1942 due to WWII recruitment.
- Before Becker, in the 1860's, French neurologist Guillaume Benjamin Amand Duchenne described in detail a slowly progessive muscular weakness in a boy, later known as Duchenne muscular dystrophy.
- The association between genetic mutations and Duchenne muscular dystrophy was made in 1986.
- In 1987, dystrophin gene on X chromosome were first implicated in the pathogenesis of Becker's muscular dystrophy.
Pathophysiology
- The pathogenesis of Becker's muscular dystrophy is characterized by muscle weakness and pseudohypertrophy (mostly proximal), cardiomyopathy, elevated CK and skelletal deformities.
- Becker's muscular dystrophy is inherited in an X-linked recessive fashion.
- Becker's muscular dystrophy is caused by a mutation in the gene DMD, one of the largest genes in humans. This gene encodes for the 3685Y aminoacid protein called dystrophin, wich can be found in skeletal and cardiac muscle, among other tisues. This mutation produces a truncated dystrophin protein that will translate into a decreased but not incomplete functionality (difference from Duchenne). Around 33% of patients with Becker's muscular dystrophy have de novo mutations. Point mutations and duplications appear mostly from spermatogenesis while deletions arise from oogenesis in most of te cases.
- On microscopic histopathological analysis, endomysial fibrosis with fatty replacement of muscle in later stages, inflammation, increased internal nuclei, myofiber cleavage with necrosis, and phagocytosis are characteristic findings of Becker's muscular dystrophy.[1]
Clinical Features
Unlike Duchenne muscular dystrophy, Becker's muscular dystrophy (BMD) phenotype presents at a later age, widely variable onset from early childhood to late adulthood, most of them falling in puberty range. Most of the patients will requiere a wheelchair after age 16.
Clinical presentation Becker's muscular dystrophy include:
- Progressive symmetric muscle weakness, with a predilection in proximal muscles (eg. pelvic, legs, shoulders)[2]
- Congestive heart failure
- Calf hypertrophy[2]
- Cramping and muscle pain after exercise[2]
- Flexion contractures[2]
- Normal neck flexor muscle strength (differenting factor of BMD from DMD)[2]
There is an abcense of fasciculations, and this finding may exclude BMD[2]
CNS is rarely afected in Becker's muscular dystrophy, for this reason, intelligence is usually spared.
Most of women are asymptomatic carriers, with very rare cases presenting the classic symptoms.
Differentiating Becker's muscular dystrophy from other Diseases
Becker's muscular dystrophy must be differentiated from other diseases that cause skelletal and cardiac muscle afection, such as:
- Duchenne muscular dystrophy. Presents with most of the symptoms of Beckers muscular dystrophy but with an earlier and more severe onset, most of them having symptoms from age 3 (Gower's sign); by convention, if a patient with a suspected dystrophinopathy stops walking before 12 years of age, he has DMD. Another diferentiating factor is the normal strength of neck flexor muscles in BMD[2]
- Limb-girdle muscular dystrophy (LGMD). Is a group of inherited autosomal conditions that are clinically similar to dystrophynopathies (muscle weakness and wasting) but occur in both sexes. They are caused by a gene mutation that encodes sarcoglycans.
- Emery-Dreifuss muscular dystrophy (EDMD). Is a neuromuscular disorder that may be inherited in an autosomal or X-linked mode. The classic clinical triad encompasses incidious muscle weakness and wasting with predilection in the humero-peroneal distribution, joint contractures in childhood, and cardiac afection that includes palpitations, and syncope.
- Spinal muscular atrophy (SMA). Presents with muscle atrophy, delayed weight and height gain, restrictive lung disease, scoliosis, joint contractures, and sleep difficulties. Is inherited in an autosomal recessive mode.[3]
- Dilated cardiomyopathy (DCM). Familial variants may be inherited in an autosomal (dominant or recessive), or an X-linked fashion. Presents with symptoms of dyspnea and poor exercise tolerance.
- Barth syndrome. Is an X-linked disorder characterized by prepubertal growth delay followed by a growth spurt, muscle weakness, cardiomyopathy, neutropenia, and facial gestalt.
Screening
- Prenatal molecular genetic testing is recomended in couples planning to conceive and have family members who are afected by or are carriers of a dystrophinopathy.
- In-utero fetal muscle biopsy has also been realized under couples request for fetuses with a high probability of beign affected and inconclusive genetic linkage.
- It is important to identify females at risk to be heterozygous of a dystrophinopathy, in order to manage possible cardiac complications; this can be done by molecular genetic testing, CK measurements, and linkage analysis.
Epidemiology and Demographics
- The prevalence of Becker's muscular dystrophy is approximately 1-3 per 100,000 individuals.
- The incidence of Becker's muscular dystrophy is approximately 3-6 per 100,000 male births worldwide.[4][5]
Age
Becker's muscular dystrophy is diagnosed in 85% of patients by age 25.
Gender
Becker's muscular dystrophy affects mostly men, women are carriers almost exclusively (except rare situation).
Race
- Becker's muscular dystrophy usually affects individuals of the hispanic race.[6]
- Asian individuals are less likely to develop Becker's muscular dystrophy.[7]
Risk Factors
- Becker's muscular dystrophy is developed in the majority of cases from males who are born from genetic carrier mothers or by spontaneous mutation,[8] there has not been any risk factors implicated for a DMD gene mutation.
- Studies have found that several genetic polymorphisms and mutations may be a factor for Becker's muscular dystrophy progression, but further research is necessary to draw conclusions.
Natural History, Complications and Prognosis
- The majority of patients with Becker's muscular dystrophy remain asymptomatic until adolescence.
- Early clinical features include calf hypertrophy, difficulty rising from a chair, proximal muscle weakness, climbing stairs, sustaining balance, elevating arms, and in later stages heart failure.[9]
- The most common complications in Becker's muscular dystrophy are cardiac and respiratory failure, pneumonias, and in rare cases cognitive impairment.
- Prognosis is generally poor, depending on spectrum of Becker's muscular dystrophy, but much better that Duchenne muscular dystrophy. In 2002, the survival rate at age 20 was 60%.
- If left untreated, the majority of patients with Becker's muscular dystrophy may die due to cardiac and respiratory failure in their mid-40's.
- Cradiac, respiratory, and orthopedic care has greatly improved in last years for patients with Becker disease, this, increasing the life span in these individuals.[10]
Diagnosis
The diagnosis of Becker's muscular dystrophy is made with a classic clinical presentation plus elevated CK, molecular genetic testing, or muscle biopsy.
Symptoms
Symptoms of Becker's muscular dystrophy may include the following:
- Proximal muscle weakness
- Myalgias
- Muscle cramps
- Imbalance
- Toe walking
- Difficulty raising from a chair
- Difficulty climbing stairs
- Difficulty raising the arms
- Heart failure
- Dyspnea
Physical Examination
Patients with Becker's muscular dystrophy usually adapt a posture with shoulders held back, abdomen stuck out, and lumbar hyperlordosis.
Physical examination may be remarkable for:
Laboratory Findings
An elevated CK is typical in Becker's muscular dystrophy, with a peak around 10-15 years of age.[11]
Other laboratory finding consistent with Becker's muscular dystrophy may be:
- Elevated ALT/AST[11]
- Myoglobinuria when strenous physical activity[11]
- Normal GGT
Hystopathology
Histologic findings in Becker's muscular may be:
- Atrophic small myofibers[11]
- Muscle fibers necrosis and regeneration[11]
- Endomysial fibrosis and fatty replacement of muscle[11]
- Inflammation[11]
EMG
EMG in Becker's muscular dystrophy, may reveal myopathic motor units with or without muscle membrane instability.
Echocardiography
Echocardiogram should be done at the time of diagnosis.
Imaging Findings
There are no X-ray findings characteristic with with Becker's muscular dystrophy, but scoliosis may be found.
Treatment
Medical Therapy
- There is no definitive treatment for Becker's muscular dystrophy; treatment will be multidisciplinary depending on comorbidities; the mainstay of therapy is supportive care.
- Corticosteroids have shown to improve strength in other dystrophinopathies, but its efficacy on Beckers muscular dystrophy is uncertain. To measure improvement with corticosteroid therapy, timed muscle function tests, pulmonary function tests, and age at loss of independent ambulation are registered.[12]
- The management of scoliosis is bracing and surgery in some cases.
- Beta-blockers, angiotensin II-receptor blockers, and ACE inhibitors are used to improve ventricular function in patients with Becker's muscular dystrophy when EF is less than 55%.
- Low impact exercise (eg. swimming) should be advised. If myalgia presents, physical activity should be reduced and myoglobinuria cheked out.
Surgery
- Cardiac transplantation may be requiered in patients with severe dilated cardiomyopathy.
Primary Prevention
There are no primary preventive measures available for Becker's muscular dystrophy.
Secondary Prevention
- Once diagnosed, patients with Becker's muscular dystrophy are followed-up every year or two years by cardiology. Follow-up testing includes pulmonary function tests, measurement of scoliosis, wheelchair depence, and cardiac assesment.[13]
- Annual influenza and pneumococcal vaccines should be given, as well vitamin D and calcium to prevent fractures.[13]
References
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