Becker muscular dystrophy (BMD) is an X-linked recessive inherited disorder characterized by slowly progressing muscle weakness of the legs and

pelvis The pelvis (: pelves or pelvises) is the lower part of an Anatomy, anatomical Trunk (anatomy), trunk, between the human abdomen, abdomen and the thighs (sometimes also called pelvic region), together with its embedded skeleton (sometimes also c ...

. It is a type of dystrophinopathy. The cause is mutations and deletions in any of the 79

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence ...

s encoding the large

dystrophin Dystrophin is a rod-shaped cytoplasmic protein, and a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. This complex is variously known as the costa ...

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

, essential for maintaining the muscle fiber's

cell membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

integrity. Becker muscular dystrophy is related to Duchenne muscular dystrophy in that both result from a mutation in the dystrophin gene, however, the hallmark of Becker is milder in-frame deletions. and hence has a milder course, with patients maintaining ambulation till 50–60 years if detected early. While there is no known cure, management strategies such as

physical therapy Physical therapy (PT), also known as physiotherapy, is a healthcare profession, as well as the care provided by physical therapists who promote, maintain, or restore health through patient education, physical intervention, disease preventio ...

, braces, and corrective surgery may alleviate symptoms. Assisted ventilation may be required in those with weakness of breathing muscles. Several drugs designed to address the root cause are currently available including

gene therapy Gene therapy is Health technology, medical technology that aims to produce a therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells. The first attempt at modifying human DNA ...

( Elevidys). Other medications used include

glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebra ...

s ( Deflazacort, Vamorolone); calcium channel blockers ( Diltiazem); to slow skeletal and cardiac muscle degeneration,

anticonvulsants Anticonvulsants (also known as antiepileptic drugs, antiseizure drugs, or anti-seizure medications (ASM)) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also used in the treatment ...

to control

seizure A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

s and some muscle activity, and

Histone deacetylase inhibitor Histone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are chemical compounds that enzyme inhibitor, inhibit histone deacetylases. Since acetylation of histones, deacetylation of histones produces transcriptionally silenced heterochromatin ...

s ( Givinostat) to delay damage to dying

muscle cell A muscle cell, also known as a myocyte, is a mature contractile Cell (biology), cell in the muscle of an animal. In humans and other vertebrates there are three types: skeletal muscle, skeletal, smooth muscle, smooth, and Cardiac muscle, cardiac ...

s. These patients do not require antisense drugs ( Ataluren, Eteplirsen, etc.) as a certain percentage of dystrophin is already expressed.

Signs and symptoms

Some symptoms consistent with Becker muscular dystrophy are: Individuals with this disorder typically experience progressive muscle weakness of the leg and pelvis muscles, which is associated with a loss of muscle mass (

wasting In medicine, wasting, also known as wasting syndrome, refers to the process by which a debilitating disease causes muscle and fat tissue to "waste" away. Wasting is sometimes referred to as "acute malnutrition" because it is believed that epis ...

). Muscle weakness also occurs in the arms, neck, and other areas, but is not as noticeably severe as in the lower half of the body. Calf muscles initially enlarge during the ages of 5–15 (an attempt by the body to compensate for the loss of muscle strength), but the enlarged muscle tissue is eventually replaced by

fat In nutrition science, nutrition, biology, and chemistry, fat usually means any ester of fatty acids, or a mixture of such chemical compound, compounds, most commonly those that occur in living beings or in food. The term often refers specif ...

and

connective tissue Connective tissue is one of the four primary types of animal tissue, a group of cells that are similar in structure, along with epithelial tissue, muscle tissue, and nervous tissue. It develops mostly from the mesenchyme, derived from the mesod ...

(pseudohypertrophy) as the legs become less used (with use of a wheelchair).

Complications

Possible complications associated with muscular dystrophies (MD) are cardiac arrhythmias. Becker muscular dystrophy (BMD) also demonstrates the following: * Mental impairment (less common in BMD than in DMD) * Pulmonary failure *

Pneumonia Pneumonia is an Inflammation, inflammatory condition of the lung primarily affecting the small air sacs known as Pulmonary alveolus, alveoli. Symptoms typically include some combination of Cough#Classification, productive or dry cough, ches ...

Genetics

The gene affected is the ''DMD '' gene, is located on the X

chromosome A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most import ...

and is inherited in an X-linked recessive pattern. Since women have two X chromosomes, if one X chromosome has the non-working gene, the second X chromosome will have a working copy of the gene to compensate, because of this ability to compensate, women rarely develop symptoms. All dystrophinopathies are inherited in an X-linked recessive manner. The risk to the siblings of an affected individual depends upon the carrier status of the mother. Carrier females have a 50% chance of passing the DMD mutation in each

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

. Sons who inherit the mutation will be affected; daughters who inherit the mutation will be carriers. Men who have Becker muscular dystrophy can have children, and all their daughters are carriers, but none of the sons will inherit their father's mutation. The ''DMD'' gene can be broken down into four different regions: the N terminal, rod, cysteine-rich, and carboxy terminal. This is the largest gene/protein in the human body, and due to its size, can have many different mutations affecting it and therefore differing clinical presentations. For example some patients with Becker's can be asymptomatic aside from blood work abnormalities, and some can present with progressive muscle weakness, heart defects, and difficulty with activities of daily living. Some literature even describes unique cases where muscle pain, cramping, and elevated creatine kinase levels are the only presenting symptoms instead of the classic presentation of muscle weakness. Becker muscular dystrophy occurs in approximately 1.5 to 6 in 100,000 male births, making it much less common than Duchenne muscular dystrophy. Symptoms usually appear in men at about ages 8–25, but may sometimes begin later. Genetic counseling may be advisable when potential carriers or patients want to have children. Sons of a man with Becker muscular dystrophy do not develop the disorder, but daughters will be carriers (and some carriers can experience some symptoms of muscular dystrophy), so the daughters' sons may develop the disorder.

Diagnosis

In terms of the diagnosis of Becker muscular dystrophy symptom development resembles that of Duchenne muscular dystrophy. A physical exam indicates a lack of pectoral and upper arm muscles, especially when the disease is unnoticed through the early teen years. Muscle wasting begins in the legs and pelvis, and then progresses to the muscles of the shoulders and neck. Calf muscle enlargement (pseudohypertrophy) is quite obvious. Among the exams/tests performed are: * Muscle biopsy (removes a small piece of muscle tissue, usually from the thigh, to check for dystrophin in muscle cells.) * Creatine kinase test (checks the level of Creatine Kinase proteins in the blood. Creatine Kinase proteins are normally found inside of healthy muscle cells, but can be found in the blood when muscle cells are damaged.) *

Electromyography Electromyography (EMG) is a technique for evaluating and recording the electrical activity produced by skeletal muscles. EMG is performed using an instrument called an electromyograph to produce a record called an electromyogram. An electromyo ...

(shows that weakness is caused by the destruction of muscle tissue rather than by damage to

nerve A nerve is an enclosed, cable-like bundle of nerve fibers (called axons). Nerves have historically been considered the basic units of the peripheral nervous system. A nerve provides a common pathway for the Electrochemistry, electrochemical nerv ...

s.) *

Genetic testing Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...

(looks for deletion, duplication, or mutation of the dystrophin gene.)

Treatment

There is no known cure for Becker muscular dystrophy yet. Treatment is aimed at control of symptoms to maximize the quality of life which can be measured by specific questionnaires. Activity is encouraged and can be considered vital for long-term survivability for these patients. Inactivity (such as bed rest) or sitting down for too long can worsen the muscle disease.

Physical therapy Physical therapy (PT), also known as physiotherapy, is a healthcare profession, as well as the care provided by physical therapists who promote, maintain, or restore health through patient education, physical intervention, disease preventio ...

may be helpful to maintain muscle strength.

Orthopedic Orthopedic surgery or orthopedics ( alternative spelling orthopaedics) is the branch of surgery concerned with conditions involving the musculoskeletal system. Orthopedic surgeons use both surgical and nonsurgical means to treat musculoskeletal ...

appliances such as braces and

wheelchair A wheelchair is a mobilized form of chair using two or more wheels, a footrest, and an armrest usually cushioned. It is used when walking is difficult or impossible to do due to illnesses, injury, disabilities, or age-related health conditio ...

s may improve mobility and self-care. Immunosuppressant steroids have been known to help slow the progression of Becker muscular dystrophy. The drug

prednisone Prednisone is a glucocorticoid medication mostly used to immunosuppressive drug, suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium ...

contributes to increased production of the protein utrophin which closely resembles dystrophin, the protein that is defective in BMD. The cardiac problems that occur with EDMD and myotonic muscular dystrophy may require a pacemaker. Other cardiomyopathies seen in Becker muscular dystrophy can also be treated with ACE inhibitors, cardiac transplant, and other personalized treatments. The investigational drug Debio-025 is a known inhibitor of the protein cyclophilin D, which regulates the swelling of

mitochondria A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...

in response to cellular injury. Researchers decided to test the drug in mice engineered to carry MD after earlier laboratory tests showed deleting a gene that encodes cyclophilin D reduced swelling and reversed or prevented the disease's muscle-damaging characteristics. According to a review by Bushby, et al. if a primary protein is not functioning properly then maybe another protein could take its place by augmenting it. Upregulation of compensatory proteins has been done in models of transgenic mice.

Prognosis

The progression of Becker muscular dystrophy is highly variable—much more so than Duchenne muscular dystrophy. There is also a form that may be considered as an intermediate between Duchenne and Becker MD (mild DMD or severe BMD). The severity of the disease may be indicated by the age of the patient at the onset of the disease. One study showed that there may be two distinct patterns of progression in Becker muscular dystrophy. Onset at around age 7 to 8 years of age shows more cardiac involvement and trouble climbing stairs by age 20, if onset is around age 12, there is less cardiac involvement. The quality of life for patients with Becker muscular dystrophy can be impacted by the symptoms of the disorder. However, with assistive devices, independence can be maintained. People affected by Becker muscular dystrophy can still maintain active lifestyles.

Research

There is no cure for any type of muscular dystrophy group. Several drugs designed to address the root cause are under development, including

( Microdystrophin), and antisense drugs ( Ataluren, Eteplirsen etc.). Other medications used include

corticosteroids Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invol ...

( Deflazacort), calcium channel blockers ( Diltiazem) to slow skeletal and cardiac muscle degeneration,

to control

s and some muscle activity, and immunosuppressants ( Vamorolone) to delay damage to dying

, braces, and corrective

surgery Surgery is a medical specialty that uses manual and instrumental techniques to diagnose or treat pathological conditions (e.g., trauma, disease, injury, malignancy), to alter bodily functions (e.g., malabsorption created by bariatric surgery s ...

may help with some symptoms while assisted ventilation may be required in those with weakness of breathing muscles. Outcomes depend on the specific type of disorder.

History

Becker muscular dystrophy is named after the German doctor Peter Emil Becker who published an article about it in 1955.

References

External links

{{DEFAULTSORT:Becker Muscular Dystrophy Rare diseases Muscular dystrophy X-linked recessive disorders