Myofibrillar Myopathy

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Myofibrillar myopathy


Myofibrillar myopathies (MFMs) are a group of skeletal muscle diseases that are frequently associated with involvement of the heart muscle. Myofibrillar myopathies can be hereditary or occur sporadically (spontaneously). The hallmark of myofibrillar disease is the abnormal accumulation of the protein desmin in the muscles, causing progressive weakness.


The term myofibrillar myopathy was proposed in 1996 as a broad term for an abnormal pattern of muscle deterioration associated with the excess accumulation of multiple proteins that include desmin. Desmin, the main muscle intermediate fiber of the cytoskeleton (the fibrous network that provides structure for the cell), is a protein in cardiac, skeletal, and smooth muscles. This protein interacts with other proteins to form a network that maintains the structure of the cell.

The main features of myofibrillar myopathies include shoulder and hip muscle deterioration, often called "limb-girdle" myopathy, along with weakness of muscles farther away from the center of the body, called distal muscle weakness. The muscles involved often include the heart, and complications such as conduction blocks, arrhythmias, and congestive heart failure are often experienced.

Most persons with myofibrillar myopathy develop the disorder due to an autosomal-dominant or autosomal-recessive inheritance pattern, which means that males and females are equally affected, and there is a 50% chance of passing on the disorder in each pregnancy. In an autosomal-recessive inheritance pattern, the affected gene is recessive and one parent is its carrier. The risk of a child being affected with myofibrillar myopathy in an autosomal-recessive inheritance pattern is 25% for each pregnancy. A lesser number of myofibrillar myopathy cases are sporadic, meaning no inheritance pattern can be found.

The pattern of weakness in this condition is often similar to patients with the other limb-girdle muscular dystrophies, but some patients have more weakness in the hands and ankles in addition to the more typical shoulder and hip weakness. Myofibrillar myopathy, like limb-girdle muscular dystrophy , slowly worsens over time, but the rate of progression is variable and some affected persons remain functional for many years.

Desmin-related myopathy (DRM) is a subgroup of myofibrillar myopathy and is the most clearly recognized type among this group. DRM was originally described as a skeletal and cardiac myopathy characterized by abnormal accumulation of desmin within muscle fibers. This definition focused attention on desmin as a key molecule associated with a diverse group of clinically and pathologically related disorders.


The true incidence of myofibrillar myopathy is unknown, but it is very rare. Both sexes are affected equally in MFM, since inheritance is usually autosomal recessive or autosomal dominant.

Causes and symptoms

Two gene mutations have been described in myofibrillar myopathy. Mutations on chromosome 2 in the gene for desmin are transmitted in an autosomal-dominant or autosomal-recessive inheritance pattern. Mutations on chromosome 11 in the gene for [.alpha]BC (alpha-B-crystallin) are transmitted in an autosomal-dominant inheritance pattern, which can also cause a desmin storage myopathy.

Defects in the function of desmin, as well as in other proteins, cause fragility of the myofibrils (structures in muscles that help them contract). In the heart, normal desmin protects the structural integrity of myofibrils during repeated muscle contractures over time. When desmin accumulates in abnormal amounts and locations of the heart muscle cell, myofibrils degrade and lose their ability to contract efficiently, resulting in weakness and inefficient pumping ability of the heart.

Myofibrillar myopathy becomes apparent in early to middle adulthood when muscle weakness in the lower extremities and gait (manner of walking) disturbances develop. The myopathy slowly progresses to also involve respiratory, facial, and heart muscles. Occasionally, this pattern is reversed and the heart muscle shows weakness before the skeletal muscles. Symptoms of alterations in the heart include abnormal rhythms that may cause fainting or, rarely, sudden death.


Diagnostic difficulties arise from the fact that the disease has many variations: in some cases, myofibrillar myopathy is a relentlessly progressive skeletal disorder with no signs of cardiac involvement, while in others, cardiomyopathy (weak heart muscle action) is the leading or even exclusive feature. Respiratory muscle insufficiency may also be a major factor in myofibrillar myopathy and is a leading cause of death.

Most of the known genetic mutations responsible for myofibrillar myopathy are autosomal dominant, but some are autosomal recessive. A significant number of the mutations also occur spontaneously without inheritance pattern. For this reason, genetic testing is critical for establishing an accurate diagnosis. The true prevalence of myofibrillar myopathy may be assessed only when most or all persons with characteristic symptoms are tested genetically.

Electromyography (EMG) and nerve conduction studies (NCSs) should be performed in all persons in whom a myofibrillar myopathy is suspected. EMG and NCSs are important to exclude causes of weakness that result from nerve malfunction, including peripheral nerve disorders. Because electromyography involves inserting a needle into a muscle, it is becoming less favored in investigating muscle weakness in children, but it still has an important role in the diagnosis of the adult disease. In myofibrillar myopathy, nerve conduction study findings are normal and EMG findings are either normal or show typical patterns of myopathies.

Muscle biopsy is an important part of the diagnostic approach because it shows myofibrillar myopathy's histologic features (i.e., its organization and effect on tissue structure). In the typical diagnostic sequence, muscle biopsy is done first, then genetic studies are pursued.

Treatment team

The treatment team of hereditary muscle diseases, depending on the needs of a particular patient, includes a neurologist , pulmonologist, cardiologist, orthopedic surgeon, physiatrist, physical therapist, orthotist, and genetic counselors.

Because the diagnosis of hereditary myopathy is often difficult, interpretation of muscle biopsy, laboratory tests, and electrodiagnostic studies should be performed by a clinician experienced in the diagnosis and treatment of neuromuscular diseases.


No specific treatment is available for any of the myofibrillar myopathies, but aggressive supportive care is essential to preserve muscle activity, to allow for maximal functional ability, and to prolong life expectancy.

The primary concerns are preventing and correcting skeletal abnormalities (e.g., scoliosis, foot deformities, and contractures) and maintaining ambulation. Aggressive use of passive stretching, bracing, and orthopedic procedures allows the affected person to remain independent for as long as possible.

Complications with the heart and lungs are the other chief concern. Early intervention to treat cardiac and respiratory insufficiency, at times requiring intermittent positive pressure ventilation (BiPAP/CPAP), can help improve function and prolong life expectancy.

Orthopedic surgery may be needed to help correct or prevent contractures (rigid muscles near joints), foot deformities, and scoliosis.

While no dietary restrictions are indicated for persons with myopathies, the diet should be tailored to the caloric needs of the patient. This may include restricting calories, especially in children with minimal mobility.

Recovery and rehabilitation

To date, there is no known treatment, medicine, or surgery that will cure MFM or stop the muscles from weakening. The goal is to prevent deformity and allow the patient to function as independently as possible. Since myofibrillar myopathy is a life-long condition that is not correctable, management includes focusing on preventing or minimizing deformities and maximizing the patient's functional ability at home and in the community.

In general, patients are given supportive care, together with leg braces and physical therapy, to maximize their ability to function in daily life. Stretching limbs to avoid tightened tendons and muscles is particularly important.

Clinical trials

As of mid-2004, there were no clinical trials recruiting participants specific for myofibrillar myopathy.


Myofibrillar myopathies are among a large group of related but distinct diseases. In general, it is expected that there will be slow progression of weakness, which worsens in affected muscles, then spreads, and progresses with time.

Heart muscle weakness and the tendency to have abnormal electrical activity of the heart can increase the risk of palpitations, fainting, and sudden death. Most patients with this group of diseases live into adulthood, but do not reach their full life expectancy.

Special concerns

Genetic counseling is often helpful to assist patients with family-planning decisions.

Vigorous physical activity is often impossible (or impractical) for patients with significant weakness, but activities like swimming, water aerobics, and low-resistance exercise equipment are often tolerated very well. The goal of these activities should be to increase the number of calories burned, but not to build strength.

Maintaining ambulation and functional ability with the aggressive use of physical therapy and bracing is highly recommended. Children and young adults are often encouraged continue with school in regular classes, with modifications designed to meet their specific physical needs.

Resources within the community may be explored. Educational institutions have resources that may be used. Adaptive physical education programs and disabled student services are generally available for qualified individuals. Access and mobility concerns in the community invariably touch upon the adjustment issues faced by individuals with a progressive disability.



Emery, Alan E. H. Muscular Dystrophy: The Facts. Oxford, UK: Oxford University Press, 2000.

Parker, James N., and Philip M. Parker, eds. The 2002 Official Patient's Sourcebook on Muscular Dystrophy. San Diego: Icon Group International, 2002.


Selcen, D., et al. "Myofibrillar Myopathy: Clinical, Morphological and Genetic Studies in 63 Patients." Brain 127 (February 2004): 439451.


"Myofibrillar Myopathy; MDA-Ask the Experts." Muscular Dystrophy Association. July 2001. (May 4, 2004 [June 2, 2004].) <>.

"Myopathy, Desmin Storage." WebMD Health. May 4, 2004 (June 2, 2004). <>.


National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Bldg. 31, Rm. 4C05, Bethesda, MD 20892-2350 or (877) 22-NIAMS (226-4267); Fax: (301) 496-8188. [email protected] <>.

Muscular Dystrophy Association. 3300 East Sunrise Drive, Tucson, AZ 85718-3208. (520) 529-2000 or (800) 572-1717; Fax: (520) 529-5300. [email protected] <>.

American Heart Association. 7272 Greenville Avenue, Dallas, TX 75231-4596. (214) 373-6300 or (800) 242-8721; Fax: (214) 373-0268. [email protected] <>.

Francisco de Paula Careta

Iuri Drumond Louro, MD, PhD