Hereditary myopathy with intranuclear filamentous


Hereditary myopathy with intranuclear filamentous, aka Inclusion body myositis (IBM) is one of a group of muscle diseases known as inflammatory myopathies, which are characterized by chronic muscle inflammation accompanied by muscle weakness. It is a slowly progressive disease, which causes a gradual deterioration of muscles that become thin and weak over the years. Most limb muscles can be affected. In particular the quadriceps (the thigh muscles which extend the knee joint), and forearm muscles that flex the wrists and fingers are commonly weak. Accordingly, patients often notice difficulty with stairs, getting out of a chair and a poor grip. Swallowing muscles are affected in some patients, but the disease typically does not affect muscles of the heart, eye, gut or bladder. It also does not affect the function of the brain or sensation, and speech is rarely affected. In general patients do not die of the disease, but most meet with some degree of disability as the disease progresses. The disease itself is painless. However, weakened muscles can predispose to injuries affecting bones, joints and soft tissues.

There are two types - sporadic inclusion body myositis (sIBM) and hereditary inclusion body myositis (hIBM)

In sIBM, two processes, one autoimmune and the other degenerative, appear to occur in the muscle cells in parallel. It usually occurs in middle to late life and is more common in men than women.

hIBM lacks some of the inflammatory characteristics of sporadic IBM. The disease develops in young adults and is caused by a wide range of genetic defects that can be passed between generations. Generally, these defects cause neuromuscular disorders characterized by muscle weakness. hIBM comprise both autosomal recessive and autosomal dominant muscle disorders that have a variable expression (phenotype) in individual patients


Sources: Wikipedia, The Myositis Association; Medpedia; Muscular Dystrophy Campaign


The symptoms of hIBM are associated with muscle weakness that lead to rapid exhaustion after physical exercise, problems in keeping the body balance and also difficulties in general body functions (swallowing, grasping).

The symptoms are:

• Frequent falling episodes (caused by weakness of main muscle of the tights, the quadriceps)

• Easy tiring after physical exertions and muscle weakness (e.g. trouble climbing stairs or standing from a seated position, or a foot that seems to drop when walking and causes tripping, or a weakened hand grip)

• Difficulty swallowing (caused by weakness of throat muscles)


Source: The Myositis Association


hIBM constitutes a heterogeneous group of disorders histologically characterized by muscle fibers with rimmed vacuoles and inclusions consisting of filaments with a diameter of 15 to 21 nm. Mutational changes in one of certain genes result in a dysfunction in structure or function of different cellular compounds of the muscle that lead to the emergence of the disease. Yet, the exact mechanisms of these diseases are not well understood.

IBM1 is an autosomal dominant disease caused by a mutation in the desmin gene of chromosome 2. This leads to a disintegration of the sarcomeric Z disc and the myofibrils, followed by abnormal ectopic accumulation of multiple proteins involved in the structure of the Z disc, including desmin, alpha-B-crystallin, dystrophin and myotilin.

IBM2 is an autosomal recessive form of hIBM, caused by a missense mutation in the GNE gene of chromosome 9 (UDP-N-Acetylglucosamine 2-Epimerase).

IBM3 is an autosomal dominant form of hIBM, caused by a missense mutation in the myosin heavy chain IIa gene on chromosome 17. This mutation could lead to conformational changes in the motor domain of the protein, which likely results in a dysfunctional myosin.


Source: Online Mendelian inheritance in Man, Wikipedia, Muscular Dystrophy Campaign


There are a number of pieces of evidence that go together to make the diagnosis of IBM:

Blood test: When muscles are damaged they release a protein into the blood stream called creatine kinase. This can be detected in a routine blood sample. In some people with IBM the level of this protein in the blood is slightly raised. This blood test may therefore alert the physician to the possibility of muscle disease.

Electromyography (EMG): When healthy muscle contract they fire off a coordinated pattern of electrical impulses that can be detected by a tiny needle positioned in the muscle. When sick muscles contract abnormal electrical impulses can be detected. However, although EMG may be helpful it cannot make a definite diagnosis.

Muscle biopsy: The definitive test for IBM is a muscle biopsy. The biopsy involves taking a small sample of muscle under local anesthetic. Laboratory analysis includes a series of stains and reactions, used to highlight different parts of the muscle. In IBM, muscle cells appear damaged. The hallmark of IBM is the inclusion body, which is an abnormal clump of proteins seen in damaged cells. This appearance will allow the pathologist and clinician to confirm the diagnosis of IBM.


Source: Muscular Dystrophy Campaign


Myositis varies tremendously from patient to patient, and no treatment works for everyone. Your physician may use a combination of drugs to treat you, or change medications over time. It is extremely important that you communicate well with your doctor about your treatment and any side effects.

The disease is generally unresponsive to corticosteroids and immunosuppressive drugs. Some evidence suggests that intravenous immunoglobulin may have a slight, but short-lasting, beneficial effect in a small number of cases. Prednisone is also used for treatment, although its benefit has not been proven.

Physical therapy may be helpful in maintaining mobility. An important part of your treatment will be the regular practice of an exercise program that works for you, no matter what your level of ability or weakness.

Talk with your physician about supplements that are sometimes recommended for muscle strength. Although no supplements are approved specifically for treating myositis, physicians and patients have found the following over-the-counter supplements helpful: Coenzyme Q10, creatine, fish oil (omega-3 fatty acid), spices like ginger and turmeric, glucosamine, vitamins A/C/E, calcium and potassium.

Occasionally, dysphagia symptoms can be severe enough that a nonsurgical expansion of the throat muscles (called "dilation") or a surgical division of specific throat muscles (called a "cricopharnygeal myotomy") may be needed.


Source: The Myositis Association, Medpedia