Pediatric Fibrodysplasia Ossificans Progressiva (Myositis Ossificans) Workup

  • Author: Robert J Pignolo, MD, PhD; Chief Editor: Lawrence K Jung, MD   more...
 
Updated: Jul 30, 2009
 

Laboratory Studies

  • Routine biochemical evaluations of bone mineral metabolism are usually normal in patients with fibrodysplasia ossificans progressiva (FOP), although the serum alkaline phosphatase activity and the erythrocyte sedimentation rate may be increased, especially during disease flare-ups.
  • Urinary basic fibroblast growth factor levels may be elevated during disease flare-ups coinciding with the preosseous angiogenic phase of early fibroproliferative lesions.
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Imaging Studies

  • Radiographic and bone scan findings suggest normal modeling and remodeling of the heterotopic skeleton.[14]
  • Bone scan findings are abnormal before heterotopic ossification (HO) can be detected on conventional radiography.
  • CT and MRI have been used to study early lesions. Although these evaluation methods are generally superfluous from a diagnostic standpoint, they can provide a useful and 3-dimensional perspective of the disease process. The definitive diagnosis of fibrodysplasia ossificans progressiva can be made by simple clinical evaluation that associates rapidly appearing soft tissue lesions with malformations of the great toes.
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Procedures

  • Definitive genetic testing of fibrodysplasia ossificans progressiva is now available.[15] Clinical suspicion of fibrodysplasia ossificans progressiva early in life on the basis of malformed great toes can lead to early clinical diagnosis, confirmatory diagnostic genetic testing (if appropriate), and the avoidance of harmful diagnostic and treatment procedures.[13] At the present time, genetic testing is available on a clinical and research basis at several laboratories.
  • Intramuscular injections must be avoided. Routine childhood diphtheria-tetanus-pertussis immunizations administered by intramuscular injection pose a substantial risk of permanent heterotopic ossification at the site of injection, as do arterial punctures, whereas measles-mumps-rubella immunizations administered by subcutaneous injection and routine venipuncture pose no significant risk.
  • Permanent ankylosis of the jaw may be precipitated by minimal soft tissue trauma during routine dental care. Assiduous precautions are necessary in administering dental care to anyone who has fibrodysplasia ossificans progressiva. Overstretching of the jaw and intramuscular injections of local anesthetic must be avoided. Mandibular blocks cause muscle trauma that leads to heterotopic ossification, and local anesthetic drugs are extremely toxic to skeletal muscle.
  • Individuals with fibrodysplasia ossificans progressiva have developmental anomalies of the temporomandibular joints (TMJs). Spontaneous or posttraumatic ankylosis of the temporomandibular joints is common and leads to severe disability with resultant difficulties in eating and poor oral hygiene. Great care must be taken not to provoke flare-ups of the temporomandibular joints. Preventive oral and dental health care measures are essential in patients with fibrodysplasia ossificans progressiva, especially during childhood years. Periodontic and preventative oral care is crucial to prevent long-term dental and oral complications in patients with fibrodysplasia ossificans progressiva.
  • Patients with fibrodysplasia ossificans progressiva have limited options for dental anesthesia. Mandibular blocks are contraindicated because they lead to ossification of the pterygoid muscles and rapid ankylosis of the temporomandibular joints. Infiltration anesthesia is difficult in the mandibular posterior molar areas of permanent teeth. Successful anesthesia in mandibular primary teeth can be achieved by infiltration through the dental pulp. Interligamentary infiltration may be helpful, if performed carefully. However, in some patients, this type of local anesthesia may not be possible. General anesthesia with awake nasotracheal fiberoptic intubation may be needed for dental care in patients with fibrodysplasia ossificans progressiva.
  • Hearing impairment is a common feature of fibrodysplasia ossificans progressiva and occurs in approximately 50% of patients. The onset is usually in childhood and may be slowly progressive. Hearing loss is usually conductive in nature and may be due to middle ear ossification; however, in some patients, the hearing impairment is neurologic in nature. Children with fibrodysplasia ossificans progressiva should generally have audiology evaluations every other year; more often, if necessary. Hearing aids are often helpful and can diminish developmental problems due to hearing loss.
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Histologic Findings

  • Histopathologic studies of fibrodysplasia ossificans progressiva lesions reveal monocytic and lymphocytic infiltration into skeletal muscle followed by widespread myocyte degeneration, fibroproliferation, chondrogenesis, and osteogenesis.[16]
  • All stages of histological development are present in the fibrodysplasia ossificans progressiva lesion within days of its induction, indicating that different regions mature at different rates.
  • Although heterotopic bone formation in fibrodysplasia ossificans progressiva is similar in some respects to bone formation in embryonic skeletal development and postnatal fracture healing, important differences include the lack of inflammation in embryonic skeletal induction and the relative absence of lymphocytic inflammatory cells in early fracture healing.
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Contributor Information and Disclosures
Author

Robert J Pignolo, MD, PhD  Assistant Professor of Medicine, Director, Ralston-Penn Clinic for Osteoporosis and Related Bone Disorders, Department of Medicine, Division of Geriatric Medicine, Associate Director, Structure-Function Biomechanical Core, Penn Center for Musculoskeletal Disorders, University of Pennsylvania School of Medicine

Robert J Pignolo, MD, PhD is a member of the following medical societies: American College of Physicians, American Geriatrics Society, American Society for Bone and Mineral Research, Gerontological Society of America, and National Osteoporosis Foundation

Disclosure: Nothing to disclose.

Coauthor(s)

Frederick S Kaplan, MD  Isaac and Rose Nassau Professor of Orthopedic Molecular Medicine, Chief, Division of Orthopedic Molecular Medicine, Director, Center for Research in FOP and Related Disorders, The University of Pennsylvania School of Medicine; Consulting Surgeon, Department of Orthopedic Surgery, Hospital of The University of Pennsylvania

Frederick S Kaplan, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Society for Bone and Mineral Research, American Society for Microbiology, Johns Hopkins Medical and Surgical Association, and Orthopaedic Research Society

Disclosure: Nothing to disclose.

Eileen M Shore, PhD  Research Associate Professor, Departments of Orthopaedic Surgery and Genetics, University of Pennsylvania School of Medicine

Eileen M Shore, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Society for Bone and Mineral Research, American Society of Human Genetics, and Royal Society of Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

David D Sherry, MD  Director, Clinical Rheumatology, Attending Physician, Pain Management, The Children's Hospital of Philadelphia; Professor of Pediatrics, University of Pennsylvania

David D Sherry, MD is a member of the following medical societies: American College of Rheumatology and American Pain Society

Disclosure: Nothing to disclose.

Daniel Rauch, MD, FAAP  Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine

Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine

Disclosure: Baxter Honoraria Consulting

Chief Editor

Lawrence K Jung, MD  Chief, Division of Pediatric Rheumatology, Children's National Medical Center

Lawrence K Jung, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Rheumatology, Clinical Immunology Society, and New York Academy of Sciences

Disclosure: Nothing to disclose.

Acknowledgments

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors Donald A Person, MD, and Mandar A Pattekar, MD, MS, to the original writing and development of this topic.

References

  1. Cohen RB, Hahn GV, Tabas JA, et al. The natural history of heterotopic ossification in patients who have fibrodysplasia ossificans progressiva. A study of forty-four patients. J Bone Joint Surg Am. Feb 1993;75(2):215-9. [Medline].

  2. Kaplan FS, Glaser DL, Shore EM, et al. The phenotype of fibrodysplasia ossificans progressiva. Clin Rev Bone Miner Metab. 2005;3:183-188.

  3. Kaplan FS, Groppe J, Pignolo RJ, Shore EM. Morphogen receptor genes and metamorphogenes: skeleton keys to metamorphosis. Ann N Y Acad Sci. Nov 2007;1116:113-33. [Medline].

  4. Shore EM, Xu M, Feldman GJ, et al. A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nat Genet. May 2006;38(5):525-7. [Medline].

  5. Kaplan FS, Xu M, Seemann P, Connor JM, Glaser DL, Carroll L, et al. Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1. Hum Mutat. Mar 2009;30(3):379-90. [Medline].

  6. Kaplan FS, Le Merrer M, Glaser DL, et al. Fibrodysplasia ossificans progressiva. Best Pract Res Clin Rheumatol. Mar 2008;22(1):191-205. [Medline].

  7. Rocke DM, Zasloff M, Peeper J, Cohen RB, Kaplan FS. Age- and joint-specific risk of initial heterotopic ossification in patients who have fibrodysplasia ossificans progressiva. Clin Orthop Relat Res. Apr 1994;243-8. [Medline].

  8. Schaffer AA, Kaplan FS, Tracy MR, et al. Developmental anomalies of the cervical spine in patients with fibrodysplasia ossificans progressiva are distinctly different from those in patients with Klippel-Feil syndrome: clues from the BMP signaling pathway. Spine (Phila Pa 1976). Jun 15 2005;30(12):1379-85. [Medline].

  9. Deirmengian GK, Hebela NM, O'Connell M, Glaser DL, Shore EM, Kaplan FS. Proximal tibial osteochondromas in patients with fibrodysplasia ossificans progressiva. J Bone Joint Surg Am. Feb 2008;90(2):366-74. [Medline].

  10. Adegbite NS, Xu M, Kaplan FS, Shore EM, Pignolo RJ. Diagnostic and mutational spectrum of progressive osseous heteroplasia (POH) and other forms of GNAS-based heterotopic ossification. Am J Med Genet A. Jul 15 2008;146A(14):1788-96. [Medline].

  11. Pignolo RJ, Foley, KL. Non-hereditary heterotopic ossification. Implications for injury, arthropathy, and aging. Clin Rev Bone Miner Metabol. 2005;3:261-266.

  12. [Guideline] Morrison WB, Dalinka MK, Daffner RH, et al. Expert Panel on Musculoskeletal Imaging. Soft tissue masses. [online publication]. Reston (VA): American College of Radiology (ACR);. 2005;6 p.

  13. Kitterman JA, Kantanie S, Rocke DM, Kaplan FS. Iatrogenic harm caused by diagnostic errors in fibrodysplasia ossificans progressiva. Pediatrics. Nov 2005;116(5):e654-61. [Medline].

  14. Kaplan FS, Strear CM, Zasloff MA. Radiographic and scintigraphic features of modeling and remodeling in the heterotopic skeleton of patients who have fibrodysplasia ossificans progressiva. Clin Orthop Relat Res. Jul 1994;238-47. [Medline].

  15. Kaplan FS, Xu M, Glaser DL, et al. Early diagnosis of fibrodysplasia ossificans progressiva. Pediatrics. May 2008;121(5):e1295-300. [Medline].

  16. Pignolo RJ, Suda RK, Kaplan FS. The fibrodysplasia ossificans progressiva lesion. Clin Rev Bone Miner Metabol. 2005;3:195-200.

 
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Extensive heterotopic ossification on the back of a patient with fibrodysplasia ossificans progressiva.
Characteristic malformed great toes and hallux valgus.
Tumorlike swellings on the back representing early fibrodysplasia ossificans progressiva (FOP) flare-ups.
Severe limb swelling seen with an fibrodysplasia ossificans progressiva (FOP) flare-up.
 
 
 
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