RESUMEN
PURPOSE: We report the first prospective, international, natural history study of the ultra-rare genetic disorder fibrodysplasia ossificans progressiva (FOP). FOP is characterized by painful, recurrent flare-ups, and disabling, cumulative heterotopic ossification (HO) in soft tissues. METHODS: Individuals aged ≤65 years with classical FOP (ACVR1R206H variant) were assessed at baseline and over 36 months. RESULTS: In total, 114 individuals participated; 33 completed the study (mean follow up: 26.8 months). Median age was 15.0 (range: 4-56) years; 54.4% were male. During the study, 82 (71.9%) individuals reported 229 flare-ups (upper back: 17.9%, hip: 14.8%, shoulder: 10.9%). After 84 days, 14 of 52 (26.9%) imaged flare-ups had new HO at the flare-up site (mean new HO volume: 28.8 × 103 mm3). Mean baseline low-dose whole-body computed tomography (excluding head) HO volume was 314.4 × 103 mm3; lowest at 2 to <8 years (68.8 × 103 mm3) and increasing by age (25-65 years: 575.2 × 103 mm3). The mean annualized volume of new HO was 23.6 × 103 mm3/year; highest at 8 to <15 and 15 to <25 years (21.9 × 103 and 41.5 × 103 mm3/year, respectively) and lowest at 25 to 65 years (4.6 × 103 mm3/year). CONCLUSION: Results from individuals receiving standard care for up to 3 years in this natural history study show the debilitating effect and progressive nature of FOP cross-sectionally and longitudinally, with greatest progression during childhood and early adulthood.
Asunto(s)
Miositis Osificante , Osificación Heterotópica , Adolescente , Adulto , Femenino , Humanos , Masculino , Miositis Osificante/diagnóstico por imagen , Miositis Osificante/epidemiología , Osificación Heterotópica/diagnóstico por imagen , Osificación Heterotópica/genética , Dolor , Estudios Prospectivos , Preescolar , Niño , Adulto Joven , Persona de Mediana EdadRESUMEN
BACKGROUND: Fibrodysplasia ossificans progressiva (FOP), an ultra-rare, progressive, and permanently disabling disorder of extraskeletal ossification, is characterized by episodic and painful flare-ups and irreversible heterotopic ossification in muscles, tendons, and ligaments. Prevalence estimates have been hindered by the rarity of FOP and the heterogeneity of disease presentation. This study aimed to provide a baseline prevalence of FOP in the United States, based on contact with one of 3 leading treatment centers for FOP (University of Pennsylvania, Mayo Clinic, or University of California San Francisco), the International Fibrodysplasia Ossificans Progressiva Association (IFOPA) membership list, or the IFOPA FOP Registry through July 22, 2020. RESULTS: Patient records were reviewed, collected, and deduplicated using first and last name initials, sex, state, and year of birth. A Kaplan-Meier survival curve was applied to each individual patient to estimate the probability that he or she was still alive, and a probability-weighted net prevalence estimate was calculated. After deduplication, 373 unique patients were identified in the United States, 294 of whom who were not listed as deceased in any list. The average time since last contact for 284 patients was 1.5 years. Based on the application of the survival probability, it is estimated that 279 of these patients were alive on the prevalence date (22 July 2020). An adjusted prevalence of 0.88 per million US residents was calculated using either an average survival rate estimate of 98.4% or a conservative survival rate estimate of 92.3% (based on the Kaplan-Meier survival curve from a previous study) and the US Census 2020 estimate of 329,992,681 on prevalence day. CONCLUSIONS: This study suggests that the prevalence of FOP is higher than the often-cited value of 0.5 per million. Even so, because inclusion in this study was contingent upon treatment by the authors, IFOPA membership with confirmed clinical diagnosis, and the FOP Registry, the prevalence of FOP in the US may be higher than that identified here. Thus, it is imperative that efforts be made to identify and provide expert care for patients with this ultra-rare, significantly debilitating disease.
Asunto(s)
Miositis Osificante , Osificación Heterotópica , Femenino , Humanos , Miositis Osificante/epidemiología , Prevalencia , Sistema de Registros , Estados Unidos/epidemiologíaRESUMEN
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, non-survivors 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 non-survivors 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.
Asunto(s)
Miositis Osificante/epidemiología , Miositis Osificante/mortalidad , Osificación Heterotópica/epidemiología , Osificación Heterotópica/mortalidad , Osteocalcina/sangre , Receptores de Activinas Tipo I/genética , Adolescente , Fosfatasa Alcalina/sangre , Niño , Preescolar , China/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Mortalidad , Mutación , Miositis Osificante/sangre , Miositis Osificante/diagnóstico , Osificación Heterotópica/sangre , Osificación Heterotópica/diagnóstico , Enfermedades Raras/sangre , Enfermedades Raras/diagnóstico , Enfermedades Raras/epidemiología , Enfermedades Raras/mortalidad , Estudios RetrospectivosRESUMEN
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.
Asunto(s)
Hallux/diagnóstico por imagen , Miositis Osificante/diagnóstico por imagen , Osificación Heterotópica/diagnóstico por imagen , Actividades Cotidianas , Adolescente , Adulto , Niño , Estudios Transversales , Progresión de la Enfermedad , Femenino , Hallux/anomalías , Humanos , Japón/epidemiología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Miositis Osificante/epidemiología , Calidad de Vida , Radiografía , Adulto JovenRESUMEN
PURPOSE: Fibrodysplasia ossificans progressiva is a rare congenital disorder that causes systemic heterotopic ossification, leading to systemic ankyloses and mobility losses. This study aimed to ascertain the natural history of fibrodysplasia ossificans progressiva. METHODS: In addition to the medical history questionnaire, patients aged 16 years and older were asked to complete activities of daily living and quality of life surveys using the Barthel Index, MOS 36-Item Short-Form Health Survey, and Health Assessment Questionnaire. The surveys were conducted over a 4-years period. RESULTS: Of the 15 participating patients, 13 reported swelling during the study period. The Barthel Index and Health Assessment Questionnaire surveys indicated a tendency for questionnaire items related to arm function to reflect early decreases in the activities of daily living. Decreases in activities of daily living functioning were closely related to decreases in the quality of life in physical function domains. Activities of daily living and quality of life were maintained at a similar level to baseline values over the study period (Barthel Index: p = 0.42, MOS 36-Item Short-Form Health Survey: p = 0.43, Health Assessment Questionnaire: p = 0.87). CONCLUSIONS: We obtained longitudinal information relating to natural history on fibrodysplasia ossificans progressiva patients. Implications for rehabilitation Fibrodysplasia ossificans progressiva is a rare congenital disease that causes heterotopic ossification of muscle tissue throughout the body, leading to systemic ankyloses and mobility losses. When the Barthel Index was high and the activities of daily living were relatively stable, the items on the Health Assessment Questionnaire that are related to arm function began to show impairment. Early focus on upper extremity function that includes the use of assistive devices during the period when a patient is still able to perform many activities of daily living is important. Although decreases in activities of daily living functioning were closely related to decreases in the quality of life in the physical function domains, the scores of the domains other than physical function were similar to the national standard score.
Asunto(s)
Actividades Cotidianas , Personas con Discapacidad , Miositis Osificante , Calidad de Vida , Adolescente , Personas con Discapacidad/psicología , Personas con Discapacidad/rehabilitación , Femenino , Humanos , Japón/epidemiología , Estudios Longitudinales , Masculino , Miositis Osificante/epidemiología , Miositis Osificante/psicología , Miositis Osificante/rehabilitación , Rendimiento Físico Funcional , Encuestas y CuestionariosRESUMEN
BACKGROUND: Rare bone diseases account for 5% of all birth defects yet very few have personalised treatments. Developments in genetic diagnosis, molecular techniques and treatment technologies however, are leading to unparalleled therapeutic advance. This review explores the evolving therapeutic landscape of genetic skeletal disorders (GSDs); the key conditions and there key differentials. METHODS: A retrospective literature based review was conducted in December 2018 using a systematic search strategy for relevant articles and trials in Pubmed and clinicaltrials.gov respectively. Over 140 articles and 80 trials were generated for review. RESULTS: Over 20 personalised therapies are discussed in addition to several novel disease modifying treatments in over 25 GSDs. Treatments discussed are at different stages from preclinical studies to clinical trials and approved drugs, including; Burosumab for X-linked hypophosphatemia, Palovarotene for Hereditary Multiple Exostoses, Carbamazepine for Metaphyseal Chondrodysplasia (Schmid type), Lithium carbonate and anti-sclerostin therapy for Osteoporosis Pseudoglioma syndrome and novel therapies for Osteopetrosis. We also discuss therapeutic advances in Achondroplasia, Osteogenesis Imperfecta (OI), Hypophosphotasia (HPP), Fibrodysplasia Ossificans Progressiva, and RNA silencing therapies in preclinical studies for OI and HPP. DISCUSSION: It is an exciting time for GSD therapies despite the challenges of drug development in rare diseases. In discussing emerging therapies, we explore novel approaches to drug development from drug repurposing to in-utero stem cell transplants. We highlight the improved understanding of bone pathophysiology, genetic pathways and challenges of developing gene therapies for GSDs.
Asunto(s)
Enfermedades Óseas/epidemiología , Enfermedades Óseas/patología , Animales , Enfermedades Óseas/metabolismo , Femenino , Humanos , Masculino , Miositis Osificante/epidemiología , Miositis Osificante/metabolismo , Miositis Osificante/patología , Osteogénesis Imperfecta/epidemiología , Osteogénesis Imperfecta/metabolismo , Osteogénesis Imperfecta/patología , Osteopetrosis/epidemiología , Osteopetrosis/metabolismo , Osteopetrosis/patología , Enfermedades Raras/epidemiología , Enfermedades Raras/metabolismo , Enfermedades Raras/patologíaRESUMEN
Myositis ossificans is a benign, solitary, frequently self-limiting, ossifying soft-tissue mass encountered often in the active sporting population. Typically occurring within skeletal muscle - most often the brachialis, quadriceps and adductor muscle groups - lesions may arise with or without a traumatic history. The exact pathophysiology of these ossifying lesions is still poorly understood. Patients present with localized pain and swelling with loss of range of motion. Plain radiographs may not be able to detect early lesions, which allows for an expanded role of ultrasonography as an early screening modality, despite magnetic resonance imaging remaining the gold standard for imaging of soft tissue masses. Conservative treatment is implemented for most patients with excellent outcomes, with surgical excision being an option for persistent symptoms or progressive disease. Typically, athletes are able to progress to light activity at 2 to 3 months, full activity by 6 months, and back to their preinjury level by 1 year.
Asunto(s)
Músculo Esquelético/patología , Miositis Osificante/epidemiología , Deportes , Atletas , Tratamiento Conservador , Humanos , Imagen por Resonancia Magnética , Miositis Osificante/diagnóstico por imagen , Radiografía , Rango del Movimiento Articular , Volver al Deporte , UltrasonografíaRESUMEN
Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare and devastating disorder characterized by cumulative episodes of progressive heterotopic ossification. It is estimated that there exist 600-700 patients in Mainland China. Nevertheless, due to the rarity, many FOP patients were initially misdiagnosed. Until now fewer than 150 patients have been identified in Mainland China. This review summarizes the epidemiology and clinical features of FOP patients, the progress of clinical and basic research in China, and the future of FOP care in China.
Asunto(s)
Miositis Osificante/diagnóstico , Miositis Osificante/epidemiología , Animales , China/epidemiología , Progresión de la Enfermedad , HumanosRESUMEN
The worldwide prevalence and risk factors for kidney stones in patients with fibrodysplasia ossificans progressiva (FOP) are unknown. We conducted a survey of 383 patient-members of the International Fibrodysplasia Ossificans Progressiva Association, comprising the entire global membership of the international FOP community. Two hundred seven patients from 31 nations and 6 continents (54%) responded. Nineteen of 207 respondents had kidney stones, revealing a worldwide prevalence of 9.2%. In a confirmatory follow-up study of subjects participating in a longitudinal FOP natural history study, 9 of 114 individuals reported a history of kidney stones (7.9%). In both study populations patients with kidney stones were found to be more functionally impaired compared to those without nephrolithiasis. The prevalence of kidney stones in the adult FOP population of the Unites States was 15.8% (9/57 individuals) compared to a sex- and age-weighted prevalence of 4.5% (p=4×10-5) in the general population. Although geographical variation exists, patients with FOP have an approximately three-fold greater prevalence of kidney stones than the general population. This unusually high prevalence may be due to high bone turnover from chronic immobilization, or to unknown mechanistic effects of the activating FOP mutation in activin A receptor, type I/activin-like kinase-2 (ACVR1/ALK2), increasing the disease burden and morbidity in this already disabling condition.
Asunto(s)
Cálculos Renales/epidemiología , Miositis Osificante/epidemiología , Adulto , Factores de Edad , Femenino , Humanos , Cálculos Renales/etiología , Cálculos Renales/metabolismo , Masculino , Persona de Mediana Edad , Miositis Osificante/complicaciones , Miositis Osificante/metabolismo , Nefrolitiasis/epidemiología , Nefrolitiasis/etiología , Nefrolitiasis/metabolismo , Prevalencia , Factores de Riesgo , Factores Sexuales , Encuestas y Cuestionarios , Adulto JovenRESUMEN
The following essays are the personal statements of two remarkable young individuals, Ian Cali and Laura Rossano, who candidly share their perspectives on living life with fibrodysplasia ossificans progressiva (FOP). These essays are excerpts from the opening comments that Ian and Laura delivered at The First and The Second International FOP Association Drug Development Forums in 2014 and 2016, respectively. We present these unedited essays in this special issue of BONE so that physicians, scientists, and researchers everywhere can glimpse the valiant challenges that envelop the lives of all individuals with FOP and can appreciate that diseases are not just biological processes but indelible human experiences. These last words belong to Ian and Laura. Frederick S. Kaplan M.D.; Eileen M. Shore Ph.D.; and Robert J. Pignolo M.D., Ph.D. - Guest Editors.
Asunto(s)
Miositis Osificante/epidemiología , China/epidemiología , Humanos , Miositis Osificante/patología , Osificación Heterotópica/epidemiología , Osificación Heterotópica/patologíaRESUMEN
BACKGROUND: Fibrodysplasia ossificans progressiva (FOP) is a rare, severely disabling, and life-shortening genetic disorder that causes the formation of heterotopic bone within soft connective tissue. Previous studies found that the FOP prevalence was about one in every two million lives. The aim of this study is to estimate the FOP prevalence in France by probabilistic record-linkage of 2 national databases: 1) the PMSI (Programme de médicalisation des systèmes d'information), an administrative database that records all hospitalization activities in France and 2) CEMARA, a registry database developed by the French Centres of Reference for Rare Diseases. RESULTS: Using a capture-recapture methodology to adjust the crude number of patients identified in both data sources, 89 FOP patients were identified, which results in a prevalence of 1.36 per million inhabitants (CI95% = [1.10; 1.68]). FOP patients' mean age was 25 years, only 14.9% were above 40 years, and 53% of them were males. The first symptoms - beside toe malformations- occurred after birth for 97.3% of them. Mean age at identified symptoms was 7 years and above 18 years for only 6.9% of patients. Mean age at diagnosis was 10 years, and above 18 years for 14.9% of the patients. FOP patients were distributed across France. CONCLUSIONS: Despite the challenge of ascertaining patients with rare diseases, we report a much higher prevalence of FOP in France than in previous studies elsewhere. We suggest that efforts to identify patients and confirm the diagnosis of FOP should be reinforced and extended at both national and European level.
Asunto(s)
Miositis Osificante/epidemiología , Adolescente , Adulto , Niño , Bases de Datos Factuales , Femenino , Francia/epidemiología , Humanos , Masculino , Prevalencia , Adulto JovenRESUMEN
The formation of lamellar bone in the soft tissues, where bone normally does not exist, is called myositis ossificans. However, it would be more accurate to describe as myositis ossificans the involvement of skeletal muscles and as ectopic or heterotopic ossification the involvement of soft tissues in general. The lesion is subdivided in genetic and non-genetic or acquired types. Myositis or fibrodysplasia ossificans progressiva is a debilitating rare genetic disorder. Clinical suspicion of the disease in the newborn on the basis of malformed great toes may lead to early clinical diagnosis, confirmatory diagnostic genetic testing and avoidance of iatrogenic harmful procedures. Acquired lesions involve the neurogenic myositis ossificans and the non-neurogenic disorder. The latter is defined either as circumscribed myositis ossificans that is post-traumatic or as idiopathic/pseudomalignant myositis ossificans that is non-traumatic and may be a form fruste of fibrodysplasia ossificans progressiva. Ossification in fibrodysplasia ossificans progressiva is irreversible, unlike other forms of heterotopic ossification. In this retrospective study, a total of 22 children with myositis ossificans treated in a 20-year period were identified and classified. Two patients were diagnosed with myositis/fibrodysplasia ossificans progressiva, one with neurogenic myositis ossificans, one with idiopathic/pseudomalignant myositis ossificans and 18 patients with circumscribed myositis ossificans. The clinical features, imaging and histological findings as well as treatment modalities and complications of myositis ossificans in our patients are presented and discussed.
Asunto(s)
Predisposición Genética a la Enfermedad , Miositis Osificante/diagnóstico por imagen , Miositis Osificante/epidemiología , Factores de Edad , Biopsia con Aguja , Niño , Preescolar , Estudios de Cohortes , Tratamiento Conservador , Bases de Datos Factuales , Progresión de la Enfermedad , Diagnóstico Precoz , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Lactante , Recién Nacido , Imagen por Resonancia Magnética/métodos , Masculino , Monitoreo Fisiológico/métodos , Miositis Osificante/genética , Miositis Osificante/patología , Procedimientos Ortopédicos/métodos , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Tomografía Computarizada por Rayos X/métodosRESUMEN
No disponible
Asunto(s)
Humanos , Miositis Osificante/epidemiología , Enfermedades Óseas/congénito , Hallux Valgus/epidemiología , Calidad de Vida , Perfil de Impacto de EnfermedadAsunto(s)
Miositis Osificante/epidemiología , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Exposición a Riesgos Ambientales , Femenino , Humanos , Recién Nacido , Masculino , Persona de Mediana Edad , Limitación de la Movilidad , Miositis Osificante/etiología , Padres , Edad Paterna , Salud Pública , Factores Socioeconómicos , España/epidemiologíaRESUMEN
Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disease that causes bone formation within the muscles, tendons, ligaments and connective tissues. There is no cure for this disorder and only treatment of the symptoms is available. The purpose of this study was to review the literature and describe the clinical, cellular and molecular aspects of FOP. The material used for the study was obtained by reviewing scientific articles published in various literature-indexed databases. In view of its rarity and of the lack of insightful information and the unpredictability of its course, FOP is a challenging disorder for professionals who are confronted by it. However, this rare disease raises a great deal of interest because understanding the mechanism of mature bone formation can encourage research lines related to bone regeneration and the prevention of heterotopic ossification.
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Bioingeniería , Miositis Osificante , Adulto , Proteínas Morfogenéticas Óseas/fisiología , Femenino , Humanos , Recién Nacido , Masculino , Miositis Osificante/diagnóstico , Miositis Osificante/epidemiología , Miositis Osificante/metabolismo , Miositis Osificante/fisiopatología , Osteogénesis/fisiología , Transducción de Señal/fisiologíaRESUMEN
La fibrodisplasia osificante progresiva es la causa más grave de osificación ectópica en humanos. Se caracteriza por malformaciones esqueléticas congénitas y placas de hueso maduro (endocondral) en el músculo y en otras estructuras ricas en tejido conjuntivo. Se produce por una mutación espontánea en el gen del receptor de la activina A tipo I, similar a la activina-cinasa-2. A raíz de este hallazgo, se han producido importantes avances en el conocimiento de su base molecular y celular. Además de permitir una mejor comprensión de los mecanismos que gobiernan la osificación, evidencias recientes indican que la alteración primordial radica en mecanismos básicos de la diferenciación celular que son clave en varias vías fisiológicas y en la génesis de enfermedades de gran impacto. En el presente artículo, resumimos los últimos avances con implicaciones que trascienden los límites de esta devastadora enfermedad para postularse como un nuevo modelo dentro de la fisiopatología humana (AU)
Fibrodysplasia ossificans progressiva is the most severe and disabling disorder of ectopic ossification in humans. It is characterized by congenital skeletal abnormalities in association with extraskeletal widespread endochondral osteogenesis. Virtually all patients show the same mutation in the «activin A type-I/activin-like kinase-2» receptor encoding gene. As a result of this discovery there have been significant advances in the knowledge of the cellular and molecular basis of the disease. Besides allowing a better understanding of ossification process, recent evidence indicates that the primary disturbance lies within basic mechanisms of cell differentiation that are key in several physiological pathways and in the genesis of diseases with a major impact on health. In this article we summarize these breakthroughs, with implications that go beyond the limits of this devastating disease to insinuate a new model of human pathophysiology (AU)
Asunto(s)
Humanos , Masculino , Femenino , Miositis Osificante/epidemiología , Miositis Osificante/prevención & control , Proteína Morfogenética Ósea 1/análisis , Proteína Morfogenética Ósea 1 , Mutación/genética , Diferenciación Celular/genética , Enfermedades Musculoesqueléticas/complicaciones , Enfermedades Musculoesqueléticas/diagnóstico , Enfermedades Musculoesqueléticas/genética , Disgenesias Tiroideas/complicaciones , Disgenesias TiroideasRESUMEN
Fibrodysplasia ossificans progressiva, an ultra-rare and disabling genetic disorder of skeletal malformations and progressive heterotopic ossification (HO), is the most catastrophic condition of skeletal metamorphosis in humans. We studied 72 patients with FOP in China and analyzed their phenotypes and genotypes comprising the world's largest ethnically homogeneous population of FOP patients. Ninety-nine percent of patients (71/72 cases) were of Han nationality; and 1% of patients (1/72 cases) were of Hui nationality. Based on clinical examination, 92% of patients (66/72 cases) had classic FOP; 4% of patients (3/72 cases) were FOP-plus; and 4% of patients (3/72) were FOP variants. Importantly, all individuals with FOP had mutations in the protein-coding region of activin A receptor, type I/activin-like kinase 2 (ACVR1/ALK2). Ninety-seven percent of FOP patients (70/72 cases) had the canonical c.617G>A (p.R206H) mutation, while 3% of FOP patients (2/72 cases) had variant mutations in ACVR1/ALK2. Taken together, the genotypes and phenotypes of individuals with FOP from the Han nationality in China are similar to those reported elsewhere and support the fidelity of this ultra-rare disorder in the world's most highly populated nation and across wide racial, ethnic, gender and geographic distributions.
Asunto(s)
Estudios de Asociación Genética , Miositis Osificante/genética , Miositis Osificante/patología , Huesos/diagnóstico por imagen , Huesos/patología , China/epidemiología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Miositis Osificante/diagnóstico por imagen , Miositis Osificante/epidemiología , Radiografía , Cintigrafía , Adulto JovenRESUMEN
La fibrodisplasia osificante progresiva es una de las enfermedades constitucionales óseas más devastadoras, y supone un ejemplo válido para establecer el papel de la asistencia primaria en la atención a las enfermedades poco frecuentes. Aunque las enfermedades raras suelen presentar alteraciones llamativas pueden remedar síntomas y signos de trastornos comunes, con riesgo de pasar desapercibidas. Por ello, todos los profesionales sanitarios deberían proceder con un grado de sospecha razonable ante un paciente con una enfermedad aparentemente común con rasgos atípicos o evolución no convencional. En el seguimiento integral e individualizado, los cuidados dispensados por el equipo de atención primaria en coordinación con otros dispositivos asistenciales, son fundamentales. La calidad de la atención a enfermedades raras no puede ser inferior a la que se presta a los demás procesos crónicos, ya que además de ser un imperativo de justicia y equidad estos pacientes son, en esencia, el «paradigma de la cronicidad» (AU)
Fibrodysplasia ossificans progressiva is one of the most devastating constitutional diseases of the bone, and may be a valid example to establish the role of Primary Care in the care of rare diseases. Although rare diseases usually present with marked anomalies, they can mimic signs and symptoms of common disorders, with the risk of going unnoticed. For this reason, all health professionals should proceed with a reasonable suspicion when confronted with a patient with an apparently common disease with atypical symptoms and a non-conventional progress. The care given by the Primary Care team along with other health care services are fundamental in the integrated and individualised follow-up. The quality of care in rare diseases must not be inferior to that provided to the other chronic diseases, since, besides being a requirement of justice and fairness, these patients are, in essence, the paradigm of chronicity (AU)