Rare Disease Report


Rare Diseases Involving Musculoskeletal Conditions

A wide range of rare conditions involve the musculoskeletal system.

Some, like Duchenne muscular dystrophy, arise from genetic problems in the muscles themselves, while others involve the nerves (eg, Charcot-Marie-Tooth disease), motor neurons (eg, amyotrophic lateral sclerosis [ALS]), or the bones (eg, osteogenesis imperfecta). Problems in other part of the body—such as mitochondrial disease or a metabolic disease like carnitine deficiency—can also lead to major problems with these systems.

Many individuals are familiar with some of these conditions, thanks ,in part, to powerful advocacy groups. Nonetheless, treatment options remain limited—although extensive research may soon change that.

Diagnosis Challenges

The diagnosis of a rare musculoskeletal disease can take relatively little time—days or weeks—or much longer. Some types manifest early in life with obvious and severe symptoms, while others emerge later.

Individuals with more mild disease might not notice any symptoms until later childhood or adulthood, delaying the search for a diagnosis. A thorough medical exam and history can help uncover  unexpected diagnostic clues. Family history can present a key clue to diagnosis in some cases, but not all.

Rare musculoskeletal diseases have diverse symptoms. Some cause muscle weakness or pain, sometimes affecting only specific muscle groups, while others cause skeletal deformation or weakness. In many conditions, other body systems are also affected (eg, problems with involuntary muscle movements or with the brain). Often, symptoms can begin gradually but then worsen as muscles or bones become permanently damaged.

Frequently, a person with a rare musculoskeletal disease will need multiple tests before clinicians can narrow in on a potential diagnosis. Initial tests might include basic blood work, electromyogram (EMG) and imaging, and muscle biopsy. Although specialized genetic tests are available for many of these conditions, they usually require an initial preliminary diagnosis on the physician’s part. A  team approach is often helpful, both in initial diagnosis and later treatment. Whereas, the final correct diagnosis may come from a neurologist, rheumatologist, orthopedist, or endocrinologist,  numerous physicians and allied health professionals can be of great service in managing a musculoskeletal disease.

After diagnosis, a patient’s family members may need to be tested as well, depending on the condition. Genetic testing can help individuals make family planning decisions. Prenatal testing is a new  possibility for fetuses known to be at risk for certain rare musculoskeletal diseases.

Online Resources

Genetic and Rare Diseases Information Center:

Clinical trials information:

List of FDA-approved orphan drugs:

Muscle disease information from the Muscular Dystrophy Association:


Each disease requires a specific treatment strategy, usually including multiple components. For most rare musculoskeletal diseases, no drugs are currently available to arrest the disease process.  Supportive treatment is the best and only option. Such treatments may involve different subspecialties; physical, occupational, and speech therapy, for instance, are often beneficial. Some people with rare musculoskeletal disorders need support for their respiratory muscles with bilevel positive airway pressure machines (or ventilators in more severe situations).

Some examples of disease-specific treatments include:

  • Riluzole (Rilutek) to slow disease progression in ALS
  • Tetrabenazine (Xenazine) to help suppress involuntary jerking in Huntington’s disease
  • Interferon gamma-1b (Actimmune) to slow the disease course in osteopetrosis
  • Botulinum toxin to suppress facial twitches in focal dystonia
  • Acetylcholinesterase inhibitors to reduce symptoms of myasthenia gravis

Clinical Trials

Research on rare musculoskeletal diseases is ongoing. Below is a sampling of current clinical trials studying potential new treatments:

  • ALS: low-dose interleukin-2
  • Duchenne muscular dystrophy: eteplirsen, drisapersen,tadalafil, VBP15, CAT-1004, ataluren.
  • Spinal muscle atrophy type 3: pyridostigmine bromide

Advocacy Support and Information

Advocacy groups provide an important resource for patients, caregivers, and clinicians, offering introductory educational materials and practical advice for dealing with these conditions, as well as more detailed information about recent research papers, current clinical trials, etc.

They are also a gateway to social support and to other families who have experience dealing with these diseases.

Below are some of the advocacy groups for rare musculoskeletal diseases. For a more complete list, refer to Appendix B of this resource guide:

Muscular Dystrophy Association:

ALS Association:

The Paget Foundation for Paget’s Disease of Bone and Related Disorders:

Huntington’s Disease Society of America:

International Fibrodysplasia Ossificans Progressiva Association:
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