Becker Muscular Dystrophy

Original Editor - Shreya Pavaskar
Top Contributors - Shreya Pavaskar, Rucha Gadgil, Uchechukwu Chukwuemeka, Kim Jackson, Kirenga Bamurange Liliane and Laura Ritchie

Introduction

Becker muscular dystrophy (BMD)—one of a spectrum of X-linked muscular dystrophies shows the same pattern of muscle involvement as seen in Duchenne muscular dystrophy (DMD), but with a more slowly progressive clinical course and loss of walking is noted in most BMD cases at about 37 years of age

Clinically Relevant Anatomy

Dystrophin is responsible for connecting the cytoskeleton of each muscle fiber to the underlying basal lamina. The absence of dystrophin stops calcium from entering the cell membrane affecting the signaling of the cell, water enters the mitochondria causing the cell the burst. In a complex cascading process that involves several pathways, increased oxidative stress within the cell damages the sarcolemma resulting in the death of the cell, and muscle fibers undergo necrosis and are replaced with connective tissue. Though, the reassessment of the hypothesis that loss of the basal lamina-cytoskeletal linkage was the major factor implicated in muscular dystrophies are been buttressed by the discovery of nitric oxide synthase (NOS), a signaling molecules which require an intact Dystrophin complex for sarcolemmal association and also, the depiction of certain limb-girdle muscular dystrophies (LGMDs) to be due to diminished sarcoglycan complex, while dystrophin complex at the sarcolemma is not impaired.

Pathological Process

BMD is a type of recessive, X-linked dystrophinopathy. Clinical variations in patients with BMD are due to differences in dystrophin mutations from exon deletions. The defect is mutation in a protein called dystrophin located in the Xp21.2 chromosome, and it can be inherited as an X-linked recessive trait. Patients without a clear X-linked pattern of inheritance may have defects in other genes, affecting the dystrophin-associated glycoproteins.

Dystrophin levels in BMD are generally 30-80% of normal, while in DMD, the levels are less than 5%.

Clinical Presentation

• Delayed developmental motor milestones might be the first observation from parents.
• Clumsy
• Frequent falls
• Difficulty rising from the floor, may show Gowers's sign (non-specific)
• Subclinical cases may manifest later in life; dilated cardiomyopathy can be the first sign of BMD.
• Contractures
• Weakness may be limited to specific proximal muscles
• Preservation of neck flexor muscle strength may be present
• Waddling gait in severe cases

Differential Diagnosis

• Duchenne Muscular Dystrophy: More severe and early onset than BMD. Prognosis is not good.
• Polymyositis: The absence of distal pseudohypertrophy helps in differentiating it from BMD.
• Spinal Muscular Atrophy: The absence of dystrophin gene mutation in a DNA probe provokes spinal muscular atrophy as an alternative diagnosis.
• Limb-girdle Muscular Dystrophy: This condition is hard to differentiate from BMD; however, calf muscle pseudohypertrophy is absent.
• Dilated Cardiomyopathy: cardiomyopathy is one of the most serious complications and the leading cause of mortality in dystrophies. But dilated cardiomyopathy can be a separate entity with a different genetic etiology or from other causes apart from muscular dystrophy.
• Emery-Dreifuss Muscular Dystrophy: Early contractures and cardiac defects help to distinguish it from BMD.
• Myasthenia Gravis: Fluctuating skeletal muscle weakness simulate the clinical presentation of BMD, but facial weakness, ptosis, and diplopia are common.
• Metabolic Myopathies: Most patients complain about muscle weakness and pain during physical activity rather than during rest.

Diagnostic Procedures

• Serum creatine kinase - moderate to severe elevation
• Dystrophin gene deletion analysis by gene analysis by several methods such as Multiplex ligation-dependant probe amplification (MLPA), fluorescence in situ hybridization (FISH), and polymerase chain reaction (PCR). MLPA is the most common method.
• Muscle biopsy with dystrophin antibody staining
• Cardiac magnetic resonance imaging (MRI) 
• Electromyography: indicated to differentiate between primary nerve process disease and myopathy.
• Nerve conduction studies - expected to be normal
• Electrocardiogram/Echocardiogram 
• Pulmonary Function Test
• X-rays to detect any bone abnormalities due to contractures and wasting of muscles, tracking scoliosis
• Liver function tests for transaminases

Outcome Measures

Outcome measures to quantify disease progression, including:

• 6‐minute walking test
• North Star ambulatory assessment scale,
• Time taken to climb four steps
• Time taken to rise from the floor
• Performance of upper limb.

One of the limitations of these measures is the fact they target either ambulant or non‐ambulant patients. However, as the disease progresses, the outcome measures change making it difficult to use a single outcome measure to analyze the patient. Studies are being carried out to create a uniform measure for muscular dystrophies.

Medical Management

• No medications are provided to patients for the specific treatment of BMD.
• Medications are administered to treat symptoms that are commonly associated with BMD (such as cardiac medications for heart disease).
• Corticosteroid medications are used to help individuals remain able to walk for as long as possible by delaying the inflammatory process.

Physiotherapy Management

• Patient and family education is important in these cases.
• Passive and Active stretching to improve joint flexibility (range of motion) and prevent or delay the development of contractures.
• Activities such as bicycle riding and swimming can be used to improve cardiovascular fitness and strength training. However, care should be taken that these activities are not strenuous or fatiguing as they can cause more harm to the muscles.
• Respiratory training - In the early stages of the condition, the physiotherapist will be involved in helping keep the child active. During later stages of the condition, the physiotherapist will help more with respiratory issues as well by using spirometry, positioning, huffing, and coughing in an efficient way.
• Improving the child's motor developmental skills and helping him reach the milestones by using Proprioceptive Neuromuscular Functioning|PNF techniques, various approaches like Roods Approach, Brunnstrom and Bobath
• Progressive resistance exercises with minimal weights without fatiguing the muscles.
• Massage can be done over the muscles to reduce pain and contractures.

Occupational Therapy

Activities of Daily Living (ADL) can be modified based on the level of impairment. Adaptations using tools can be done using aids like dressing sticks, grab bars, modified dinner sets, handles, raised toilet seats, etc. Items can be placed at lower levels for wheelchair-bound patients.

Orthosis

Mobility concerns are addressed, including the need for devices to assist with mobility, such as a scooter or a fully adapted wheelchair with a custom seat and back, custom supports, and electric power.

Speech Therapy

Dysphagia concerns may be evaluated by a speech therapist. Clinical evaluation may result in the recommendation to avoid specific food textures and liquid viscosities, as well as to avoid certain positions during feeding.

Recreational Therapy

Avocational needs, desires, and hobbies can be motivated to promote the well-being and overall physical health of the individual. These activities should be evaluated based on the child's interests and capabilities. Various musical instruments, dances, crafts, art as well as yoga can be learned or motivated in the child.

Complications

Complications may arise in the form of:

• cardiomyopathy, progressive loss of pulmonary and liver functions, loss of ambulation, cognitive impairment, and bone fractures.
• high chance of postoperative chest infections.
• Rhabdomyolysis leading to myoglobinuria and subsequent kidney failure.
• corticosteroids causing adrenal insufficiency and immunosuppression.

Resources

Muscular Dystrophy

Duchenne Muscular Dystrophy - A Case Study