FOP in China and Japan: An overview from domestic literatures

Jiao, Shuliang; Zhang, Yasu; Ma, Wenhao; Haga, Nobuhiko

doi:10.1002/ajmg.a.35771

Cited by 5 publications

(4 citation statements)

References 7 publications

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“…Previous researches of FOP usually focused on clinical features and genetic patterns of FOP patients [1,13,14]. However, few study described clinical outcomes in FOP patients.…”

Section: Discussionmentioning

confidence: 99%

Serum osteocalcin level is associated with the mortality in Chinese patients with Fibrodysplasia ossificans progressiva aged ≤18 years at diagnosis

She

Ran

Fang

et al. 2020

BMC Musculoskelet Disord

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Background: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder characterized by extraskeletal heterotopic ossification. It is well recognized that FOP can lead to a devastating condition of disability. However, the mortality rate of FOP patients in China and risk factors for mortality are still largely unclear. Methods: We conducted a retrospective research on a cohort of 65 cases of FOP patients in China from 2008 to 2018. We reviewed medical records of these FOP patients to retrieve information such as date of birth/death, gender, clinical features, genotypes and biochemical parameters and analyze the correlation of these parameters with the mortality. Results: 92.3% (60/65 cases) patients were classic FOP patients, 3.1% (2/65 cases) were FOP-plus and 4.6% (3/65 cases) were FOP variants. 9 cases of this cohort were dead during the ten-year period, and the overall mortality rate was 13.8%. c.617G > A mutation was confirmed in all non-survivors. In FOP patients≤18 years at diagnosis, nonsurvivors demonstrated significantly lower blood osteocalcin and alkaline phosphatase levels compared with survivors (P < 0.05), and spearman correlation and logistic regression analysis indicated that serum osteocalcin and alkaline phosphatase levels were negatively correlated with the mortality. Furthermore, the receiver-operating characteristic curve analysis showed serum osteocalcin had the largest area under the curve of 0.855 among four biochemical parameters, and serum osteocalcin < 65.9 ng/ml displayed a good capacity to discriminate the nonsurvivors from survivors in FOP patients aged 18 years and younger at diagnosis. Conclusions: Our findings showed that the mortality rate of FOP was 13.8% in China. Serum OC level was negatively correlated with the mortality in Chinese FOP patients ≤18 years at diagnosis.

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“…Previous researches of FOP usually focused on clinical features and genetic patterns of FOP patients [1,13,14]. However, few study described clinical outcomes in FOP patients.…”

Section: Discussionmentioning

confidence: 99%

Serum osteocalcin level is associated with the mortality in Chinese patients with Fibrodysplasia ossificans progressiva aged ≤18 years at diagnosis

She

Ran

Fang

et al. 2020

BMC Musculoskelet Disord

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“…These atypical signs include tibial osteochondromas ( Box 1 ), spinal malformations and broad femoral neck, which are usually reported among patients with R206H and Q207E missense mutations, and thumb malformations, cognitive impairment and diffuse scalp thinning, which are reported among patients with other atypical missense mutations in ACVR1 ( Qi et al, 2017 ). Several recent reports have also documented delayed-onset HO and absence of characteristic great toe malformations among patients with atypical mutations, who are thus categorised as FOP variants ( Jiao et al, 2013 ). Debilitating effects Starting with neck stiffness and a local flare-up episode, the cervical spine becomes involved early during the course of the disease ( Pignolo et al, 2011 ).…”

Section: Diagnosis and Managementmentioning

confidence: 99%

Fibrodysplasia ossificans progressiva: current concepts from bench to bedside

Kaliya-Perumal

Carney

Ingham

2020

Disease Models &Amp; Mechanisms

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Heterotopic ossification (HO) is a disorder characterised by the formation of ectopic bone in soft tissue. Acquired HO typically occurs in response to trauma and is relatively common, yet its aetiology remains poorly understood. Genetic forms, by contrast, are very rare, but provide insights into the mechanisms of HO pathobiology. Fibrodysplasia ossificans progressiva (FOP) is the most debilitating form of HO. All patients reported to date carry heterozygous gain-of-function mutations in the gene encoding activin A receptor type I (ACVR1). These mutations cause dysregulated bone morphogenetic protein (BMP) signalling, leading to HO at extraskeletal sites including, but not limited to, muscles, ligaments, tendons and fascia. Ever since the identification of the causative gene, developing a cure for FOP has been a focus of investigation, and studies have decoded the pathophysiology at the molecular and cellular levels, and explored novel management strategies. Based on the established role of BMP signalling throughout HO in FOP, therapeutic modalities that target multiple levels of the signalling cascade have been designed, and some drugs have entered clinical trials, holding out hope of a cure. A potential role of other signalling pathways that could influence the dysregulated BMP signalling and present alternative therapeutic targets remains a matter of debate. Here, we review the recent FOP literature, including pathophysiology, clinical aspects, animal models and current management strategies. We also consider how this research can inform our understanding of other types of HO and highlight some of the remaining knowledge gaps.

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“…In 1913, Goto reported a 4‐year‐old male patient with FOP as the first Japanese patient (article in German). A survey of case reports written in Japanese, using a journal database, revealed that, by 2012, FOP was described for 21 males and 20 females – in total 41 patients …”

Section: Epidemiologymentioning

confidence: 99%

Fibrodysplasia ossificans progressiva: Review and research activities in Japan

Haga

Nakashima

Kitoh³

et al. 2020

Pediatrics International

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Fibrodysplasia ossificans progressiva (FOP) is a rare genetic skeletal disorder manifesting progressive heterotopic ossification (HO) and congenital malformation of the great toes. Since 2007, we have conducted research on FOP. Here, we review the findings on FOP published to date, including the results of our research. Epidemiological studies in Japan have indicated that FOP has nearly the same prevalence in Japan as in the rest of the world. Basic research on its pathoetiology has progressed rapidly since the identification of the causal gene in 2006. Clinical and radiological findings have been thoroughly researched, including early radiological signs, and diagnostic criteria were established, designating FOP as an intractable disease in Japan. In patients with FOP, the progression of HO is associated with numerous disabilities, often manifesting in vicious cycles that can lead to early mortality. Through cross-sectional and short-term longitudinal studies, we have explored patient education, quality of life, and activities of daily living among Japanese patients. The management of FOP requires education of patients and caregivers, the use of medications to settle inflammation and flare-ups, instructions to ensure proper oral care, and other compensatory approaches that aid in rehabilitation. An avoidance of medical intervention, which may cause HO to progress, is also important. The advent of new drugs to prevent HO could have clinical benefit.

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FOP in China and Japan: An overview from domestic literatures

Cited by 5 publications

References 7 publications

Serum osteocalcin level is associated with the mortality in Chinese patients with Fibrodysplasia ossificans progressiva aged ≤18 years at diagnosis

Serum osteocalcin level is associated with the mortality in Chinese patients with Fibrodysplasia ossificans progressiva aged ≤18 years at diagnosis

Fibrodysplasia ossificans progressiva: current concepts from bench to bedside

Fibrodysplasia ossificans progressiva: Review and research activities in Japan

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