Journal of Neurology

, Volume 259, Issue 12, pp 2636–2643 | Cite as

Neurological symptoms in individuals with fibrodysplasia ossificans progressiva

  • Joseph A. KittermanEmail author
  • Jonathan B. Strober
  • Lixin Kan
  • David M. Rocke
  • Amanda Cali
  • Jeannie Peeper
  • Jennifer Snow
  • Patricia L. R. Delai
  • Rolf Morhart
  • Robert J. Pignolo
  • Eileen M. Shore
  • Frederick S. Kaplan
Original Communication


Fibrodysplasia ossificans progressiva (FOP), a rare, disabling condition caused by gain-of-function mutations of a bone morphogenetic protein (BMP) type I receptor, leads to episodes of heterotopic ossification and resultant immobility. Neurological problems have not been associated with FOP, but neurological symptoms are commonly reported by FOP patients. To determine the prevalence of neurological symptoms and their characteristics in individuals with FOP, we conducted a survey of the 470 patient members of the International FOP Association (IFOPA) using a questionnaire about neurological symptoms. There were 168 responses (105 females, 63 males; age 1.5–68 years) from 30 countries representing 36 % of IFOPA members. Chronic neurological symptoms were reported by 86 (51 %). Prevalence of neuropathic pain (NP) was significantly increased (P < 0.001) compared to the general population, and tenfold more common in females (15 %) than males (1.6 %). Of those with NP, 94 % reported other sensory abnormalities. Prevalence of recurrent severe headaches (HA) (26 %) was similar to that in the general population, but prevalence in females with FOP (36 %) was almost fourfold greater than in males. Prevalence of NP, HA, and other sensory abnormalities was substantially higher in post-pubertal females; 33 % reported symptoms worsened during menstrual periods. Worsening of neurological symptoms during FOP flare-ups was reported by 23 %. Three patients with FOP (1.8 %) reported myoclonus, a prevalence much greater than reported in the general population (P < 0.001). Our worldwide survey indicates that neurological symptoms are common in FOP. We speculate that these symptoms are related to effects of dysregulated BMP signaling on the central and/or peripheral nervous systems.


ACVR1 Bone morphogenetic protein 4 Substance P 



The authors thank the FOP patients and their families who participated in this study, and the staff members of the IFOPA who provided assistance with the study. This study was supported in part by the International Fibrodysplasia Ossificans Progressiva Association, the Center for Research in FOP and Related Disorders, the Ian Cali Endowment for FOP Research, the Whitney Weldon Endowment for FOP Research, the Isaac and Rose Nassau Professorship of Orthopaedic Molecular Medicine (to FSK), the Penn Center for Musculoskeletal Disorders, and the National Institutes of Health (NIH R01-AR41916).

Conflicts of interest


Supplementary material

415_2012_6562_MOESM1_ESM.doc (128 kb)
Supplementary material 1 (DOC 129 kb)


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Joseph A. Kitterman
    • 1
    • 2
    Email author
  • Jonathan B. Strober
    • 1
    • 3
  • Lixin Kan
    • 4
  • David M. Rocke
    • 5
    • 6
  • Amanda Cali
    • 7
  • Jeannie Peeper
    • 7
  • Jennifer Snow
    • 7
  • Patricia L. R. Delai
    • 8
  • Rolf Morhart
    • 9
  • Robert J. Pignolo
    • 10
  • Eileen M. Shore
    • 10
  • Frederick S. Kaplan
    • 10
  1. 1.Department of PediatricsUniversity of California San FranciscoSan FranciscoUSA
  2. 2.Cardiovascular Research InstituteUniversity of California San FranciscoSan FranciscoUSA
  3. 3.Department of NeurologyUniversity of California San FranciscoSan FranciscoUSA
  4. 4.Department of NeurologyNorthwestern University Feinberg School of MedicineChicagoUSA
  5. 5.Division of Biostatistics, Department of Public Health Sciences, School of MedicineUniversity of California DavisDavisUSA
  6. 6.Department of BiostatisticsUniversity of California DavisDavisUSA
  7. 7.International Fibrodysplasia Ossificans Progressiva AssociationWinter SpringsUSA
  8. 8.Orthopaedic Department of Santa Casa de Misericórdia de São Paulo School of MedicineSão PauloBrazil
  9. 9.Department of PediatricsKlinikum Garmisch-Partenkirchen GmbHGarmisch-PartenkirchenGermany
  10. 10.Department of Orthopaedic Surgery, Perelman School of Medicine, Center for Research in FOP and Related DisordersUniversity of PennsylvaniaPhiladelphiaUSA

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