Rare Classroom: Fibrodysplasia Ossificans Progressiva

Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The disease that we will be learning about today is:

Fibrodysplasia Ossificans Progressiva

This disease is also known as myositis ossificans progressiva or Münchmeyer disease.

What is Fibrodysplasia Ossificans Progressiva (FOP)?

  • Fibrodysplasia ossificans progressiva (FOP), is a genetic disease that triggers the conversion of muscle and other tissue into bone.
  • Extra-skeletal bone formation [heterotopic ossification (HO)] causes progressive loss of mobility as the joints become affected
  • Occurs in approximately 1 in 2 million people worldwide. Several hundred cases have been reported.
  • There is no cure or approved treatment​; the disorder is ultimately severely debilitating.
  • All individuals with classic FOP have malformations of the great toes at birth
  • Around 285 people in the United States are diagnosed with FOP
  • Misdiagnosis is frequent due to the rarity of the disease
  • Misdiagnosis can lead to unnecessary invasive procedures, such as biopsies, as well as permanent complications from medical interventions, including loss of mobility

How Do You Get It?

  • Sex
    • Present in males and females equally​
  • Age Onset
    • Most children develop episodic, painful inflammatory soft tissue swellings (or flare-ups) during the first decade of life​
  • Genetic Factors
    • In most cases, FOP is caused by a new mutational event in a child who has unaffected parents and no prior family history​
      • Caused by mutations in ACVR1, a gene that encodes for the ACVR1 receptor protein
    • Inheritance from an affected parent to his/her children has been identified in a small number of families. When genetic transmission occurs, the inheritance pattern is autosomal dominant.​
  • Hereditary Factors
    • Both genetic and environmental factors affect the characteristics of FOP. A study of three pairs of monozygotic twins with FOP found that within each pair, congenital toe malformations were identical. However, postnatal HO varied greatly depending on life history and environmental exposure. This study indicated that genetic determinants strongly influence disease characteristics during prenatal development, and that environmental factors strongly influence postnatal progression of HO.​
  • Race and Ethnicity Factors
    • No ethnic or racial patterns​
  • Environmental Factors
    • Unknown​
  • Risk factors do not directly cause FOP but certain things can worsen the condition including:​
    • Trauma to the muscles​
    • Viral illness​
    • Intramuscular injections​
    • Surgeries​
    • Falls – even minor in nature ​

What Are The Symptoms?

  • Malformed big toes​
    • Observed at birth – cause few problems but is an early sign of FOP​
  • Symptoms usually begin in the first two decades of life​
  • Inflamed swellings, typically in the shoulder and back areas and sometimes on the scalp or head, are usually the first signs.​
    • The swellings eventually clear up, but they leave behind a new piece of mature bone.​
    • Often begins in the neck and shoulders and progresses along the back, trunk, and limbs of the body​
  • People who have FOP experience different rates of new bone formation​
  • Extra bone formation tends to occur in the neck, shoulders, and upper back early in life and in the hips and knees during adolescence or early adulthood​
    • Progressive bone formation in areas of the body where bone is not normally present (heterotopic ossification)
  • Any trauma to the muscles of an individual with FOP (a fall or an invasive medical procedure) may trigger episodes of muscle swelling and inflammation followed by more rapid ossification in the injured area. 
  • Spontaneous flare-ups of the disease arise in defined temporal and spatial patterns, resulting in ribbons and sheets of bone that fuse the joints of the axial and appendicular skeleton, entombing a patient in a skeleton of heterotopic bone. 

How Is It Treated?

  • Goal: Alleviate symptoms and slow progression
  • Modification of activity, improvement in household safety, use of ambulatory devices, and use of protective headgear are all strategies to prevent falls and minimize injury when falls occur
  • Occupational therapy and vocational education consultations may be useful
  • Treatment typically provided by experts in FOP. Typically these are physicians with a background in orthopedics.
  • No FDA approved treatments available
  • Medication can be used during flares which may reduce inflammation and edema​
    • Typically a brief 4-day course of high-dose corticosteroids, started within the first 24 hours of a flare-up​
    • The use of corticosteroids should be limited to:​
      • The extremely early symptomatic treatment of flare-ups that affect major joints, the jaw, the submandibular area​
      • The prevention of flare-ups following major soft tissue injury (severe trauma)​
      • The prevention of flare-ups in emergent, elective, and minor surgeries such as dental surgery, hypospadias repair, appendectomies, etc.​
  • For muscle spasm and fiber shortening, cyclobenzaprine, metaxalone, or Lioresal can be used​
    • They may help to decrease muscle spasm and maintain more functional activity​
  • NSAIDs, cox-2 inhibitors, narcotics and oral or intravenous glucocorticoids (to manage pain)
  • Surgery should be avoided unless absolutely necessary​
    • Attempts to surgically remove heterotopic bone risks provoking explosive and painful new bone growth​
  • Biopsies of fibrodysplasia ossificans progressiva lesions are never indicated and may cause additional heterotopic ossification​
  • Intramuscular immunizations and injections should be avoided ​
  • Strategies to prevent falls and minimize injury are recommended. Some recommendations include: modification of activity, improvement in household safety, use of ambulatory devices, use of protective headgear​
  • Great care is necessary in administering dental care, particularly in avoiding overstretching of the jaw and intramuscular injections of local anesthetic ​

Where Can I Learn More???

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