Fibrodysplasia ossificans progressiva (FOP) is a rare disabling genetic disorder characterized by progressive postnatal heterotopic ossification leading to cumulative disability. Heterotopic bone formation in FOP usually begins in early childhood following a series of painful, post-traumatic, inflammatory soft-tissue swellings known as flare-ups, which later undergo ossification resulting in the progressive immobilization of the chest wall, limbs and jaw by early adulthood. Pregnancy in FOP has occurred infrequently and reproductive decisions are a dilemma for an individual or couple with FOP. We present the clinical course, medical management and potential concerns of four cases of pregnancy in FOP.
ConnorJM, EvansDAP. Fibrodysplasia ossificans progressiva: the clinical features and natural history of 34 patients. J Bone Joint Surg Br1982;64:76–83
2.
KaplanFS, GlaserDL, ShoreEM, The phenotype of fibrodysplasia ossificans progressiva. Clin Rev Bone Miner Metab2005;3:183–8
3.
KaplanFS, Le MerrerM, GlaserDL, Fibrodysplasia ossificans progressiva. Best Pract Res Clin Rheumatol2008;22:191–205
4.
ShoreEM, FeldmanGJ, XuM, KaplanFS. The genetics of fibrodysplasia ossificans progressiva. Clin Rev Bone Min Metab2005;3:201–4
5.
ShoreEM, XuM, FeldmanGJ, A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressive. Nat Genet2006;38:525–7
6.
KaplanFS, XuM, SeemannP, Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1. Hum Mutat2009;30:379–90
7.
RogersJG, ChaseGA. Paternal age effect in fibrodysplasia ossificans progressiva. J Med Genet1979;16:147–8
8.
KaplanFS, McCluskeyW, HahnG, TabasJ, MuenkeM, ZasloffMA. Genetic transmission of fibrodysplasia ossificans progressiva. J Bone Joint Surg1993;75-A:1214–20
9.
HebelaN, ShoreEM, KaplanFS. Three pairs of monozygotic twins with fibrodysplasia ossificans progressiva: the role of environment in the progression of heterotopic ossification. Clin Rev BoneMiner Metab2005;3:205–8
10.
KaplanFS, GlaserDL, ShoreEM, Hematopoietic stem-cell contribution to ectopic skeletogenesis. J Bone Joint Surg Am2007;89:347–57
11.
KaplanFS, GroppeJ, PignoloRJ, ShoreEM. Morphogen receptor genes and metamorphogenes: skeleton keys to metamorphosis. Ann NY Acad Sci2007;1116:113–33
12.
KaplanFS, ShenQ, LounevV, Skeletal metamorphosis in fibrodysplasia ossificans progressiva. J Bone Miner Metab2008;26:521–30
13.
LounevV, RamachandranR, WosczynaMN, . Identification of progenitor cells that contribute to heterotopic skeletogenesis. J Bone Joint Surg (Am)2009;91:652–63
14.
KanL, LiuY, McGuireTL, Dysregulation of local stem/progenitor cells as a common cellular mechanism for heterotopic ossification. Stem Cells2009;27:150–6
15.
PignoloRJ, SudaRK, KaplanFS. The fibrodysplasia ossificans progressiva lesion. Clin Rev Bone Miner Metab2005;3:195–200
16.
YuPB, DengDY, LaiCS, BMP type I receptor inhibition prevents ectopic ossification in mouse model of fibrodysplasia ossificans progressiva (FOP). Nat Med2008;14:1363–9
17.
KittermanJA, KantanieS, RockeDM, KaplanFS. Iatrogenic harm caused by diagnostic errors in fibrodysplasia ossificans progressiva. Pediatrics2005;116:654–61
18.
KaplanFS, XuM, GlaserDL, Early diagnosis of fibrodysplasia ossificans progressiva. Pediatrics2008;121:e1295–300
19.
KaplanFS, GlaserDL. Thoracic insufficiency syndrome in patients with fibrodysplasia ossificans progressiva. Clin Rev Bone Miner Metab2005;3:213–6
20.
KussmaulWG, EsmailAN, SagarY, RossJ, GregoryS, KaplanFS. Pulmonary and cardiac function in advanced fibrodysplasia ossificans progressiva. Clin Orthop Rel Res1998;346:104–9
21.
HairMS, PeeperJL. The international fibrodysplasia ossificans progressiva association. Clin Rev Bone Miner Metab2005;3:267–9
22.
KaplanFS, and The International Clinical Consortium on Fibrodysplasia Ossificans Progressiva. The medical management of fibrodysplasia ossificans progressiva: current treatment considerations. Clin Proc Intl Clin Consort FOP2008;3:1–82
23.
DavidsonBN, BowermanRA, LaFerlaJJ. Myositis ossificans progressiva and pregnancy: a therapeutic dilemma. J Reprod Med1985;30:945–7
ThorntonYS, BirnbaumSJ, LebowitzN. A viable pregnancy in a patient with myositis ossificans progressive. Am J Obstet Gynecol1987;156:577–8
26.
RhenT, CidlowskiJA. Anti-inflammatory action of glucocorticoids- new mechanisms for old drugs. N Engl J Med2005;353:1711–23
27.
LounevVY, RamachandaranR, WosczynaMN, Identification of progenitor cells that contribute to heterotropic skeletogenesis. J Bone Joint Surg Am2009;91:652–63
28.
MeierR, BolligerKP. Anaesthesiologic problems in patients with fibrodysplasia ossificans progressive. Anaesthesist1996;45:631–4
29.
SchafferAA, KaplanFS, TracyMR, Developmental anomalies of the cervical spine in patients with fibrodysplasia ossificans progressiva are distinctly different from those in patients with Klippel-Feil syndrome. Spine2005;30:1379–85
