Types of Muscular Dystrophy
Muscular dystrophy refers to a group of genetic diseases that cause progressive muscle weakness and loss. There are more than 30 types of muscular dystrophy, all with different causes and symptoms. Though the most common types appear during childhood, other forms affect adults only. Some of the more common types of muscular dystrophy are summarized below.
Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy, accounting for about a third of all muscular dystrophies. The condition, which leads to progressive deterioration of muscle fibers, usually affects boys, but girls can also carry the mutated gene and experience some symptoms.
Duchenne is caused by a mutation in the DMD gene, which provides instructions for making a protein called dystrophin. There are many different types of mutations associated with DMD, with most leading to no, or very little, functional dystrophin being produced. Dystrophin maintains the structure of muscle fibers, so without dystrophin, a patient’s muscles gradually degrade.
The DMD gene is located on the X chromosome, so DMD is an X-linked disease and mostly affects males because they have only one copy of the X chromosome. Because females have two X chromosomes, the second one can compensate for the mutated DMD gene by producing enough functional dystrophin protein to either prevent the symptoms of Duchenne or cause only mild symptoms. However, these individuals are so-called “carriers” who can pass the disease to their children.
Duchenne’s progression is relatively rapid compared with other types of muscular dystrophy. Boys typically begin showing signs of the disease between ages 1 and 6 and usually need to use a wheelchair before they reach their early teens. Boys usually experience muscle atrophy initially in muscles surrounding the hips and shoulder region. In addition to skeletal muscle atrophy, DMD patients also experience weakening of the heart and diaphragm muscles in later stages of the disease.
There is currently no cure for Duchenne, but there are several treatments available that can slow the progression of the disease, including exon-skipping therapies, which work like a molecular patch, so that the DMD gene can produce a shorter version of the dystrophin protein to help protect and maintain the strength of muscle fibers. Other therapies include corticosteroids to increase muscle strength and angiotensin-converting enzyme (ACE) inhibitors and beta-blockers to slow heart muscle deterioration.
Becker Muscular Dystrophy
Becker muscular dystrophy is a condition in which skeletal and heart muscles slowly degrade. The causes and symptoms of Becker are similar to those of Duchenne muscular dystrophy, though the disease’s progression is typically slower. This type is named after Peter Emil Becker, the German doctor who first described the differences between this disease and Duchenne in the 1950s.
Becker, like Duchenne, is caused by a mutation in the DMD gene, which provides instructions for making the dystrophin protein. This type of muscular dystrophy can develop as a result of mutations that cause reduced levels of dystrophin, or a smaller and less efficient dystrophin protein, to be produced. Over time, damaged muscle cells weaken and die, resulting in muscular weakness.
Like DMD, Becker is also an X-linked disease, so the condition mostly affects males. A man with Becker will always pass the mutation on to his daughters, but never to his sons, as sons inherit the Y chromosome from their father. If a girl inherits one mutated copy of the DMD gene, she is a carrier and is at risk of passing the mutation to her children, possibly without knowing that she was carrying a faulty gene or showing any symptoms of the disease.
Becker is less common and milder than Duchenne, and it worsens at a much slower rate. The initial symptoms may include cramping and reduced stamina during exercise, due to muscle weakness in the lower parts of the body. Muscle loss usually begins in hips, the pelvic area, thighs, and shoulders. Becker may cause only mild skeletal muscle problems but severe cardiac problems.
As symptoms may vary among patients, different healthcare professionals may need to be involved to address each person’s specific needs. Therapeutic strategies may involve physical therapy, which can aid in managing symptoms by stretching tight muscles, helping to maintain their function longer. Other treatments such as ACE inhibitors and beta blockers to help lessen the workload of the heart and slow the deterioration of heart muscle.
Facioscapulohumeral Muscular Dystrophy
Facioscapulohumeral muscular dystrophy (FSHD) is a muscle-wasting disease associated with the progressive weakening of the muscles starting in the face, shoulders, and upper arms. Generally, the progression of the disease is fairly slow, but both the age of onset and the degree of severity of the condition can vary greatly among patients, with symptoms potentially beginning as early as infancy or as late as adulthood. Most patients first show symptoms in their 20s and 30s.
There are two types of FSHD, both caused by changes in a region of DNA near the end of chromosome 4, known as the D4Z4 region. This disease results from hypomethylation — fewer methyl groups binding to DNA — of the D4Z4 region, resulting in an overactive DUX4 gene. Depending on the mechanism of hypomethylation, a person will either have FSHD type 1 (FSHD1), the most common form, or FSHD type 2 (FSHD2).
FSHD1 is inherited in an autosomal dominant manner, in which the individual inherits a malfunctioning chromosome 4 from either the mother or father. In most FSHD1 patients, the number of D4Z4 repeats is reduced substantially (1-10 repeats instead of 11-100) in one of the inherited chromosomes. In individuals with FSHD2, the number of D4Z4 repeats is not altered or deleted. However, in 80% of FSHD2 patients, another gene called SMCHD1 is mutated.
Symptoms of FSHD may take a very long time to develop. Most patients are not diagnosed with the disease until their 20s, and some may not notice indications until their 50s. The muscle atrophy associated with FSHD is characteristically asymmetric, which may cause initial disease symptoms to be confused with muscle strains or sports injuries. Other symptoms may include hip and lower leg weakness, eye issues, and pain and inflammation.
Medications that show promise in treating other types of muscular dystrophies have not been of benefit in managing FSHD, and no approved therapy exists that can cure or reverse its symptoms. However, there are several options for the medical management of this muscular dystrophy that can help improve patients’ quality of life and reduce the risk of related complications.
Limb-Girdle Muscular Dystrophy
Limb-girdle muscular dystrophy (LGMD) is the name given to a varied collection of neuromuscular disorders with different genetic causes. The limb-girdle is the bony structure surrounding the shoulder and hip joints. This type of muscular dystrophy is characterized by muscle atrophy in the limb-girdle regions of the body, or in the muscles around the shoulders and hips.
LGMD is an inherited disorder that occurs as a result of mutations in many different genes. These genes are usually the ones that provide instructions for producing proteins required for muscle maintenance and repair. These mutations result in the abnormal function of muscle proteins, which leads to muscle weakness.
The inheritance pattern of LGMD varies and depends on the form or subtype of the disease, which depends on the specific genetic mutation causing it. The different subtypes of LGMD can be broadly categorized under two inheritance patterns, autosomal dominant and autosomal recessive. Autosomal means that the genes involved are present on the autosomes or non-sex chromosome, the X and the Y chromosome. So both males and females have the same probability of developing the disease.
LGMD results in gradual muscle weakness in the hips and shoulders, or the limb-girdle area. As the disease progresses, muscle atrophy, or wasting, can also affect muscles in the arms, legs, hands, and feet. Although all types have similar symptoms, the severity, age of onset, and progression of symptoms vary widely among patients and even among those in the same family.
Due to the differences in symptoms among LGMD patients, developing a treatment regimen can take time. Clinicians typically recommend that patients try different splints and orthotics to hopefully improve the function of hands and feet. Some clinicians may advise low-impact exercises, such as swimming and water aerobics, as a way of maintaining muscle tone.
Oculopharyngeal Muscular Dystrophy
Oculopharyngeal muscular dystrophy (OPMD) is a genetic disease that is characterized by muscle wasting, or atrophy. As its name implies, muscles that control the eyelids (oculo) and throat (pharyngeal) are typically the first affected in patients. Although the progression is typically slow, the speed of progression and specific symptoms vary greatly from patient to patient.
OPMD is caused by mutations in the PABPN1 gene, which contains the instructions for making the polyadenylate binding protein (PABPN1). At least 10 different mutations in PABPN1 have been identified that can cause OPMD. All result in a PABPN1 protein with a longer stretch of the same amino acid — the building blocks of proteins — that is called alanine.
OPMD can be inherited in two distinct patterns: autosomal recessive or autosomal dominant. For autosomal recessive, if a parent has the disease (that is, two copies of the disease-causing mutation) all of his/her children will be carriers. For autosomal dominant, a single copy of the disease-causing mutation is sufficient to cause the disease.
Symptoms of OPMD typically first appear when patients reach middle age (about 40–60 years old). The initial symptoms are droopy eyelids and difficulty swallowing caused by the weakening of muscles around the eyes and throat. Eye muscle degeneration can progress and lead to difficulty moving the eyes and sometimes to double vision.
Treatments for OPMD focus on managing the symptoms experienced by the patients. Different therapeutic strategies may be employed for symptoms such as ptosis (drooping of the upper eyelid), dysphagia (difficulty swallowing), and general muscle weakness. Occupational therapy may also help when weakness in the upper arms and shoulders makes it difficult to perform daily tasks.
Tibial Muscular Dystrophy
Tibial muscular dystrophy (TMD) is a form of distal muscular dystrophy in which there is weakness and atrophy in the ankle muscles, progressing to the muscles of the shinbone or tibia in the front of the lower leg. Also called Udd distal myopathy, this type is particularly prevalent in Finland, affecting at least 1 in every 10,000 people.
TMD is caused by mutations in the TTN gene, which provides instructions for making the titin protein. This protein plays an important role in the contraction and relaxation of muscles. It is the largest protein in the sarcomeres, the basic units of a muscle. Mutations in the TTN gene alter the structure and function of the titin protein and disrupt its interactions with other sarcomere-related proteins.
The TTN gene is located on chromosome 2, which is an autosomal (non-sex) chromosome. Everyone has two copies of the TTN gene, one inherited from the mother, the other from the father. TMD is inherited in an autosomal dominant pattern. A person with TMD has a 50% chance of passing the disease to their children. If both parents have the disease, there is a 75% chance their children will inherit the disease.
The main symptoms of TMD are muscle weakness and cardiomyopathy, or heart muscle disease. For most patients, symptoms of muscle weakness start after age 35. Patients might find it difficult to walk or may feel their ankles are weak. Cardiomyopathy is more likely to occur in patients with the early-onset form of the disease.
Like most other muscular dystrophies, there is no cure for TMD. Management of symptoms includes physiotherapy and occupational therapy to improve muscle strength and minimize the risk of injury. In more severe cases, using leg braces or wheelchairs to aid in mobility may be necessary. Regular monitoring for any heart issues is also important.
Myotonic dystrophy is the most common type of late-developing muscular dystrophy. Although it can appear at any age, it usually presents itself in adults in their 20s and 30s. The condition is progressive, so symptoms of muscle stiffness and weakness tend to worsen over time. People with myotonic dystrophy typically experience extended muscle contractions and have difficulty relaxing muscles after use.
There are two types of myotonic dystrophy, both caused by genetic mutations. Myotonic dystrophy type 1 is caused by an abnormal expansion in a region of the DMPK gene; type 2 is caused by an expansion in the CNBP gene. In certain cases, these abnormal expansions can appear just after birth, in which case the condition is called congenital myotonic dystrophy.
Myotonic dystrophy is inherited in an autosomal dominant pattern. The DMPK and CNBP genes are both located on an autosome, or non-sex chromosome. The DMPK gene is located on chromosome 19, while the CNBP gene is found on chromosome 3. Dominant means that one mutated copy of the gene is sufficient to cause the disease.
Patients with mild type 1 often have cataracts, or clouded eye lenses, and muscles that fail to relax after use. Muscle weakness and wasting are typical symptoms of this type. Type 2 almost exclusively develops in adults and is generally the milder of the two forms. Proximal muscles, or those closer to the center of the body, tend to be more affected in this type.
Due to the variation in symptoms of myotonic dystrophy, specific therapy plans are generally developed for each individual. There are, however, several general medical management strategies that can help the majority of patients, including physical and occupational therapy, respiratory management, and treatments for heart issues. Treatment is focused on maintaining patients’ quality of life.
Emery-Dreifuss Muscular Dystrophy
Emery-Dreifuss muscular dystrophy (EDMD) is a rare, slowly progressive genetic disorder that affects skeletal and heart muscles. This type of muscular dystrophy is characterized by the wasting and weakness of muscles in the shoulders, upper arms, and calves. It can also cause stiff joints in the elbows, neck, and heels. Patients commonly have a heart problem called a conduction block that can be very serious.
EDMD can be caused by mutations in three different genes: EMD, FHL1, and LMNA. The EMD gene provides instructions for making a protein called emerin, which is made in many types of cells but is particularly important in skeletal and cardiac muscle cells. The FHL1 gene provides instructions for making three versions of a protein (FHL1A, FHL1B, and FHL1C) that play a role in muscles. The LMNA gene provides instructions to make several slightly different proteins called lamins.
When EDMD is caused by mutations in the EMD or FHL1 genes, it is inherited in an X-linked recessive pattern. Males are more likely than females to develop this type of dystrophy. In most cases caused by mutations in the LMNA gene, the disease is inherited in an autosomal dominant pattern. LMNA gene mutations can rarely be inherited in an autosomal recessive pattern.
Toe-walking is often seen in the initial stages of this dystrophy due to stiffness in the Achille’s tendon, which makes landing on the heels painful. Gradual progression of muscle weakness is seen, along with wasting of muscles in the shoulders, upper arms, and calves. Contractures (stiffness) in joints are also observed in the early stages. Heart problems and biochemical abnormalities can also occur.
There is currently no specific treatment for EDMD. Therapies focus on alleviating symptoms such as joint deformities and heart problems that are common in patients. Stretching and range-of-motion exercises, in consultation with a trained physiotherapist, can help slow the development of joint stiffness and deformity. Occupational therapy can help patients adapt their activities to compensate for the loss of muscle strength.
Congenital Muscular Dystrophies
Congenital muscular dystrophies is the name given to a group of muscular dystrophies that lead to muscle weakness and wasting from birth or very early on in life. They are caused by genetic mutations that may be inherited or be the result of new mutations. There are several types of congenital muscular dystrophies.
Bethlem myopathy, named after the Dutch doctor who first described it in 1976, is a rare and progressive form of muscular dystrophy. The condition mainly affects skeletal muscles and, to an extent, connective tissues. Recently, Bethlem myopathy was classified as one of the forms of LGMD.
Fukuyama Congenital Muscular Dystrophy
Fukuyama congenital muscular dystrophy is is found almost exclusively in Japan, where it is the most common form of the disease after DMD, , affecting from 2-4 infants per 100,000 births. Infants born with FCMD exhibit weak crying, weak suckling, and weak muscle tone (also called hypotonia).
Muscle-eye-brain disease is a type of muscular dystrophy that begins at birth. It is reported mostly in patients from Finland, although it has been observed in several other countries. It is an inherited condition that primarily affects, as the name suggests, skeletal muscles, eyes, and the brain.
Rigid Spine Muscular Dystrophy
Rigid spine muscular dystrophy, sometimes referred to as rigid spine syndrome, is a type of congenital muscular dystrophy. It involves weakness of the muscles of the torso and neck, and can cause spine stiffness and serious breathing problems.
Ullrich Congenital Muscular Dystrophy
Ullrich congenital muscular dystrophy is a rare hereditary muscle condition that manifests at birth or a few months after birth. It belongs to a group of disorders called collagen type 6-related myopathies and characterized by abnormalities in collagen type 6, a major protein that supports skeletal muscles.
Walker Warburg Syndrome
Walker-Warburg syndrome is an inherited disorder that affects the development of muscles, eyes, and the brain. It is the most severe form of congenital muscular dystrophy, with most affected individuals not surviving past age 3.