Fibrodysplasia ossificans progressiva: clinical and genetic aspects.
Fibrodysplasia ossificans progressiva: clinical and genetic aspects.
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DOI：
10.1186/1750-1172-6-80
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发表时间：
2011-12-01
影响因子：
3.7
通讯作者：
Kaplan FS
中科院分区：
文献类型：
--
作者：
Pignolo RJ;Shore EM;Kaplan FS
进行性骨化性纤维发育不良（FOP）是一种严重致残的遗传性结缔组织疾病，其特征是大脚趾先天性畸形和进行性异位骨化，在特征性骨外部位形成定性正常骨。全球患病率约为1/2，000，000。FOP不存在种族、民族、性别或地理偏好。患有FOP的儿童在出生时表现正常，除了大脚趾的先天性畸形。在生命的前十年，软组织疼痛发作（突发）时有发生，通常由软组织损伤、肌内注射、病毒感染、肌肉拉伸、福尔斯或疲劳引起。这些突然发作将骨骼肌、肌腱、韧带、筋膜和腱膜转变为异位骨，使运动变得不可能。非典型形式的FOP患者已被描述。他们要么表现出FOP的经典特征加上一个或多个非典型特征[FOP +]，要么表现出FOP的两个经典定义特征之一或两者的主要变异[FOP变体]。经典FOP由编码I型激活素A受体/激活素样激酶2（一种骨形态发生蛋白（BMP）I型受体）的基因ACVR 1/ALK 2中的复发性激活突变（617 G>A; R206 H）引起。非典型FOP患者在保守氨基酸中也存在杂合ACVR 1错义突变。FOP的诊断是通过临床评估。可进行确认性基因检测。鉴别诊断包括进行性骨异型增生、骨肉瘤、水肿、软组织肉瘤、硬纤维瘤、侵袭性幼年纤维瘤病和非遗传性（获得性）异位骨化。虽然大多数FOP病例是散发性的（非遗传性突变），但少数遗传性FOP病例显示常染色体显性模式的生殖系传播。目前，还没有明确的治疗方法，但在发作的前24小时内开始的高剂量皮质类固醇的短暂4天疗程可能有助于减少疾病早期阶段的强烈炎症和组织水肿。预防性管理基于对福尔斯、呼吸下降和病毒感染的预防措施。平均寿命约为40岁。大多数患者在生命的第二个十年结束时需要坐轮椅，并且通常死于胸廓功能不全综合征的并发症。
Fibrodysplasia ossificans progressiva (FOP) is a severely disabling heritable disorder of connective tissue characterized by congenital malformations of the great toes and progressive heterotopic ossification that forms qualitatively normal bone in characteristic extraskeletal sites. The worldwide prevalence is approximately 1/2,000,000. There is no ethnic, racial, gender, or geographic predilection to FOP. Children who have FOP appear normal at birth except for congenital malformations of the great toes. During the first decade of life, sporadic episodes of painful soft tissue swellings (flare-ups) occur which are often precipitated by soft tissue injury, intramuscular injections, viral infection, muscular stretching, falls or fatigue. These flare-ups transform skeletal muscles, tendons, ligaments, fascia, and aponeuroses into heterotopic bone, rendering movement impossible. Patients with atypical forms of FOP have been described. They either present with the classic features of FOP plus one or more atypical features [FOP plus], or present with major variations in one or both of the two classic defining features of FOP [FOP variants]. Classic FOP is caused by a recurrent activating mutation (617G>A; R206H) in the gene ACVR1/ALK2 encoding Activin A receptor type I/Activin-like kinase 2, a bone morphogenetic protein (BMP) type I receptor. Atypical FOP patients also have heterozygous ACVR1 missense mutations in conserved amino acids. The diagnosis of FOP is made by clinical evaluation. Confirmatory genetic testing is available. Differential diagnosis includes progressive osseous heteroplasia, osteosarcoma, lymphedema, soft tissue sarcoma, desmoid tumors, aggressive juvenile fibromatosis, and non-hereditary (acquired) heterotopic ossification. Although most cases of FOP are sporadic (noninherited mutations), a small number of inherited FOP cases show germline transmission in an autosomal dominant pattern. At present, there is no definitive treatment, but a brief 4-day course of high-dose corticosteroids, started within the first 24 hours of a flare-up, may help reduce the intense inflammation and tissue edema seen in the early stages of the disease. Preventative management is based on prophylactic measures against falls, respiratory decline, and viral infections. The median lifespan is approximately 40 years of age. Most patients are wheelchair-bound by the end of the second decade of life and commonly die of complications of thoracic insufficiency syndrome.
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影响因子：
1.8
作者：
Pignolo, Robert J.;Foley, Kristin L.
通讯作者：
Foley, Kristin L.
影响因子：
2
作者：
Adegbite, N. S.;Xu, M.;Kaplan, F. S.;Shore, E. M.;Pignolo, R. J.
通讯作者：
Pignolo, R. J.
影响因子：
8
作者：
Kaplan, Frederick S.;Xu, Meiqi;Shore, Eileen M.
通讯作者：
Shore, Eileen M.
影响因子：
3
作者：
Schaffer, AA;Kaplan, FS;Kusumi, K
通讯作者：
Kusumi, K
影响因子：
30.8
作者：
Shore, EM;Xu, MQ;Kaplan, FS
通讯作者：
Kaplan, FS