( fibrodysplasia 5, ossificans progressiva, FOP), 4 (myositis ossificans progressiva, MOP) FOP, FOP FOP FOP ACVR1 ACVR1. (c.617 G > A; R206H) 3

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Janice Neal
7 years ago
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1 685 doi: / j.issn ( ) : (FOP) 4 FOP ACVR ACVR1 (c.617 G > A; R206H) 3 2 FOP ; ; [ (7): ] : ; ; : R394 : A : (2011) Fibrodysplasia ossificans progressiva: 4 cases report and literature review YIN Lei ZHOU Yun-fang WANG Jian JIANG Yue-lian YING Da-ming SHEN Yong-nian CHEN Hui-jin (Special Consultation Clinic for Rare Disease & the Difficult and Complicated Cases Shanghai Children s Medical Center Affiliated to Shanghai Jiaotong University School of Medicine Shanghai China) Abstract: Objective To explore the main features and the treatment of fibrodysplasia ossificans progressiva (FOP) a rare autosomal dominant inherited disease. Methods The clinical manifestation the radiographic feature mutational analysis of the ACVR1 gene and the follow-up record were collected and analyzed in 4 children with FOP and the literatures relevant to FOP were reviewed. Results All four FOP cases had no family history and the ages of onset were before ten years old. Three of them had the malformation of great toes. There were had episodic soft tissue swellings in all four cases three of which had the occurrence of the multiple hetorotopic ossifications. The heterozygous missense mutation of ACVR1 (c.617g > A; R206H) was identified in one case that had the mutational analysis of the ACVR1 gene. Three cases developed ossifications after accepting invasive diagnostic procedures. Two cases were treated with Alendronate for more than one year and without any effect. Conclusions The majority of FOP patients have the congenital malformation of great toes. The early clinical manifestation of FOP is episodic soft tissue swellings and then the soft connective tissues are transformed into the mature bone. FOP can be diagnosed by the mutational analysis of ACVR1. There is no effective treatment for FOP at present. The focus of the management should be focus on early diagnosis as well as avoidance of deep soft tissue trauma and preventing all iatrogenic harm. (J Clin Pediatr201129(7): ) Key words: fibrodysplasia ossificans progressiva; malformation of great toes; gene analysis ( fibrodysplasia 5 [1] ossificans progressiva FOP) 4 (myositis ossificans progressiva MOP) FOP FOP 1 FOP 1 7 FOP 2 ~ 1 : : zhouyfqq@126.com

2 ( 1C) X ( 1D) ACVR1 : c.617g > A(p.Arg206His); 9 ( 2) 1 1 (20 mg / d) 1 8 : 10 cm : IgE X 3 ~ 4 : c.617g > A ( p. 2 8 Arg206His); ACVR d : 8 d 6 S ( 1A B) 2 ~ 4 : A. ; B. S ; C. ; D. X 1 2 X

3 687 8 cm 6 cm X X X [2] ( ) [3-5] Patin FOP 1868 Von Dusch [6] : 10 X 2-3 [7] 4 ; ; ( 2) FOP FOP 1 FOP ; 3 41 [7] ; 4 1 X FOP 2 4 FOP FOP 4 ACVR

4 FOP (%) > > 95 > 90 > 90 / ~ 50 2q23-24 IA [11] FOP (activin receptor IA ACVR1) I FOP 3 FOP ( bone morphogenetic protein BMP) FOP FOP 4 FOP FOP Jones [13] FOP ACVR1 617 G > A(R206H) G > A 982 G > A G > A 619 G > A [8] 2 ACVR1 FOP (617G > A; R206H) > 95 > [10] GNAS1 1 FOP ACVR1 FOP POH ACVR1 FOP ; ; 3 [12] FOP ACVR1 BMP FOP FOP 3 FOP [14] 90% FOP FOP 35 FOP ACVR1 [1 9] 3 FOP FOP ( progressive osseous heteroplasia POH) Albright (Albright hereditary osteodystrophy AHO) ACVR1 Dorsomophin

5 689 BMP [7] Kaplan FS Glaser DL Shore EM et al. The phenotype SMAD 1 / 5 / 8 FOP of fibrodysplasia ossificans progressiva [J]. Clin Rev Bone [15] Miner Metab20053(3-4): BMP I FOP [8] Kaplan FS Xu M Seemann P et al. Classic and atypical FOP fibrodysplasia ossificans progressiva (FOP) phenotype are CD20 caused by mutation in the bone morphognetic protein B (BMP) type I receptor ACVR1 [J]. Hum Muta [16] FOP 25 (3): FOP [9] Zaghloul KA Heuer GG Guttenberg MD et al. Lumbar FOP puncture and surgical intervention in a child with FOP undiagnosed fibrodysplasia ossificans progressiva [J]. J FOP Neursurg Pediatrics20081(1): [10] Ahmed SF Barr DG Bonthron DT. GNAS1 Mutations and progressive osseous heteroplasia [J]. N Engl J Med2002 [17] FOP 346(2): FOP [11] Pignolo RJ Suda RK Kaplan FS. The fibrodysplasia Gatti [18] ossificans progressiva lesion [J]. Clin Rev Bone Miner FOP Metab20053(3-4): [12] Kaplan FS Shore EM Glaser DL et al. The medical [19] FOP management of fibrodysplasia ossificans progressive: current FOP treatment considerations [J]. Clin Proc Intl Consort FOP 20051(3):1-71. [13 ] Jones MK Wang H Peskar BM et al. Inhibition of angiogenesis by nonsteroidal anti-inflammatory drugs: insight into mechanisms and implications for cancer growth and ulcer healing [J]. Nat Med19995(12): : [14] Simmons FER. Advances in H1-antihistamines [J]. N Engl J Med (21): : [1] Kaplan FS Xu M Glaser DL et al. Early diagnosis of fibrodysplasia ossificans progressiva [J]. Pediatrics (5):e1295-e /5/8 through type 1 BMP receptor [J]. Biorheology (1): [16] Altschuler EL. Consideration of Rituximab for fibrodysplasia [2] Hebela N Shore EM Kaplan FS. Three pairs of monozygotic ossificans progressiva [J]. Med Hypotheses twins with fibrodysplasia ossificans progressiva: the (3): role of environment in the progression of heterotopic ossification [J]. Clin Rev Bone Miner Metab20053 (3-4): [17] Kaplan FS Glaser DL Shore EM et al. Hematopoietic stem-cell contribution to ectopic skeletogenesis[j]. J Bone Joint Surg Am200789(2): [3]. [18] Gatti D Viapiana O Rossini M et al. Rosiglitazone [J] (4): therapy is associated with major clinical improvement in a [4]. 5 patient with fibrodysplasia ossificans progressive [J]. J [J] (6): Bone Miner Res201025(6): [5] Guo H Peng D Xu M et al. Report of two FOP cases [19] Bocciardi R Ravazzolo R. Is there a biological basis for with 617 G > A mutation in the ACVR1 gene from Chinese treatment of fibrodysplasia ossificans progressiva with population [J]. Clin Dysmorphol201019(4): rosiglitazone? Potential benefits and undesired effects [6] Kaplan FS. Fibrodysplasia Ossificans Progressiva: an [DB / OL]. PPAR Res historical perspective [J]. Clin Rev Bone Miner Metab ( : ) 20053(3-4): [15] Rath B Nam J Deschner J et al. Biomechanical forces exert anabolic effects on osteoblasts by activation of SMAD

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