Development of Macrocycle Kinase Inhibitors for ALK2 Using Fibrodysplasia Ossificans Progressiva-Derived Endothelial Cells.

Fibrodysplasia ossificans progressiva (FOP) is an extremely rare congenital form of heterotopic ossification (HO), caused by heterozygous mutations in the activin A type I receptor (ACVR1), that encodes the bone morphogenetic protein (BMP) type I receptor ALK2. These mutations enable ALK2 to induce downstream signaling in response to activins, thereby turning them into bone-inducing agents. To date, there is no cure for FOP.

Risk factors for central nervous system tumors in children: New findings from a case-control study.

Background: Central nervous system tumors (CNS) are the most frequent solid tumor in children. Causes of CNS tumors are mainly unknown and only 5% of the cases can be explained by genetic predisposition. We studied the effects of environmental exposure on the incidence of CNS tumors in children by subtype, according to exposure to industrial and/or urban environment, exposure to crops and according to socio-economic status of the child.

Risk of bone tumors in children and residential proximity to industrial and urban areas: New findings from a case-control study.

Few epidemiologic studies have explored risk factors for bone tumors in children, and the role of environmental factors needs to be analyzed. Our objective was to ascertain the association between residential proximity to industrial plants and urban areas and risk of bone tumors in children, taking into account industrial groups and toxic pollutants released. A population-based case-control study of childhood bone cancer in Spain was carried out, covering 114 incident cases obtained from the Spanish Registry of Childhood Tumors (between 1996 and 2011), and 684 controls individually matched by sex, year of birth, and autonomous region of residence.

Monitoring Huntington's Disease Mortality across a 30-Year Period: Geographic and Temporal Patterns.

Background: Huntington's disease (HD) is a progressive neurodegenerative condition characterized by chorea, dystonia, behavioral disturbances and cognitive decline. The aim of this study is to assess temporal and spatial changes on mortality attributable to HD over 30 years in Spain.

Methods: HD data were extracted from the nationwide mortality registry for the period 1984-2013.

Residential proximity to environmental pollution sources and risk of rare tumors in children.

Background: Few epidemiologic studies have explored risk factors for rare tumors in children, and the role of environmental factors needs to be assessed.

Objectives: To ascertain the effect of residential proximity to both industrial and urban areas on childhood cancer risk, taking industrial groups into account.

Methods: We conducted a population-based case-control study of five childhood cancers in Spain (retinoblastoma, hepatic tumors, soft tissue sarcomas, germ cell tumors, and other epithelial neoplasms/melanomas), including 557 incident cases from the Spanish Registry of Childhood Tumors (period 1996-2011), and 3342 controls individually matched by year of birth, sex, and region of residence.

Agricultural crop exposure and risk of childhood cancer: new findings from a case-control study in Spain.

Background: Childhood cancer is the main cause of disease-related death in children in Spain. Although little is known about the etiology, environmental factors are potential explanations for a fraction of the cases. Previous studies have shown pesticides to be associated with childhood cancer.

Risk of neuroblastoma and residential proximity to industrial and urban sites: A case-control study.

Background: Neuroblastoma is the most common extracranial solid tumor in children but its etiology is not clearly understood. While a small fraction of cases might be attributable to genetic factors, the role of environmental pollution factors needs to be assessed.

Objectives: To ascertain the effect of residential proximity to both industrial and urban areas on neuroblastoma risk, taking into account industrial groups and toxic substances released.

Association between residential proximity to environmental pollution sources and childhood renal tumors.

Background: Few risk factors for childhood renal tumors are well established. While a small fraction of cases might be attributable to susceptibility genes and congenital anomalies, the role of environmental factors needs to be assessed.

Objectives: To explore the possible association between residential proximity to environmental pollution sources (industrial and urban areas, and agricultural crops) and childhood renal cancer, taking into account industrial groups and toxic substances released.

Osteochondromas in fibrodysplasia ossificans progressiva: a widespread trait with a streaking but overlooked appearance when arising at femoral bone end.

Metaphyseal bony outgrowths are a well-recognized feature of fibrodysplasia ossificans progressiva (FOP) phenotype, but its genuine frequency, topographic distribution, morphological aspect, and potential implications are not fully established. To better ascertain the frequency and characteristics of osteocartilaginous exostoses in FOP disease, we conducted a cross-sectional radiological study based on all the traceable cases identified in a previous comprehensive national research. Metaphyseal exostoses were present in all the 17 cases of FOP studied.

Childhood leukemia and residential proximity to industrial and urban sites.

Background: Few risk factors for the childhood leukemia are well established. While a small fraction of cases of childhood leukemia might be partially attributable to some diseases or ionizing radiation exposure, the role of industrial and urban pollution also needs to be assessed.

Objectives: To ascertain the possible effect of residential proximity to both industrial and urban areas on childhood leukemia, taking into account industrial groups and toxic substances released.

Childhood vasculitis hospitalizations in Spain, 1997-2011.

The aim of this study is to describe the childhood vasculitis hospital burden in Spain (1997-2011), considering type of disease, hospitalization rates and time trends. Data were obtained from the National Discharges Basic Minimum Data Set (National Patient Data Base). Inpatient events of children younger than 15 years of age were analyzed.

Monostotic Paget's disease of the femur: a diagnostic challenge and an overlooked risk.

Background: Although radiological diagnosis of Paget's disease of bone (PD) is usually straightforward, monostotic cases may potentially raise specific problems which lead to performing invasive procedures. Therefore, the purpose of this study is to ascertain whether or not monostotic femoral Paget's disease (MFPD) presentation poses particular diagnostic difficulties which prompt excessive use of excisional biopsies.

Methods: We retrospectively reviewed the medical records of 24 MFPD patients identified from a series of 412 patients; their clinical features were compared with those of the remaining 164 monostotic cases and the radiological images were systematically assessed.

Mortality of congenital osteochondrodysplasias: a nationwide registry-based study.

Osteochondrodysplasias are a heterogeneous group of more than 200 entities, characterized by abnormalities of cartilage, bone growth, and skeletal development. The aim of this study was to assess temporal and spatial changes in overall mortality due to these disorders in Spain, using data from a nationwide registry. Annual deaths showing osteochondrodysplasias as the underlying cause of death were selected using the International Classification of Diseases-9th revision (ICD-9) codes for the period 1981 through 1998, and ICD-10 codes for the period 1999 through 2008.

Epidemiology of hereditary ataxias in Spain: hospital discharge registry and population-based mortality study.

Background: Hereditary ataxias (HA) comprise a group of genetically heterogeneous rare diseases. As important public health problems to be monitored, this study analyses the morbimortality of HA in Spain.

Methods: Data were extracted from the national death index (1981-2008), using the International Classification of Diseases (ICD) 9th revision code 334 until 1998, and 10th revision code G11 from 1999 onwards.

[Is there a place in primary care for rare diseases? The case of fibrodysplasia ossificans progressiva].

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.

Further evidence supporting a genetic background for Paget's disease of bone in Spain.

The aim of this paper is to investigate heritable factors that might be related to the recognised genetic susceptibility for developing Paget's disease of bone (PD). This was a hospital-based, case-control study of a systematically selected group of PD patients and a group of controls drawn from the same health setting. In these populations we assessed surname pattern, parental consanguinity and constitutional physical traits.

Implications of a new radiological approach for the assessment of Paget disease.

In the present study, we quantified the proportion of skeletal involvement of Paget disease of bone (PDB) not captured by an abdominal X-ray. We also analyzed extension and severity over time and tested the hypothesis that X-rays from selected areas could replace bone scans for mapping PBD. We examined whole skeletal (99m)TC-MDP bone scans from 208 consecutive untreated patients.

Fibrodysplasia ossificans progressiva in Spain: epidemiological, clinical, and genetic aspects.

We aimed to investigate the epidemiological determinants, clinical features, and genetic pattern of FOP in our country by evaluating the entire population of patients identified according to a combination of methods. To achieve this, 24 individuals were confirmed as FOP cases, 17 of whom were alive at the end of 2011 (point prevalence=0.36 × 10(-6)).

[Implications of the new etiophatogenic approach in the classification of constitutional and genetic bone diseases].

Recent years have seen an unprecedented increase in the knowledge and understanding of biochemical disturbances involved on constitutional bone disorders. Recognition of the genetic background as the common cause of these diseases prompted the substitution of the term «constitutional» by «genetic», in referring to them. Understanding physiopathological bases by finding out the altered metabolic pathways as well as their regulatory and control systems, favours an earlier and more accurate diagnosis based on interdisciplinary collaboration.

Public health research on rare diseases.

Despite the low prevalence of Rare Diseases (RD), over 30 million EU citizens suffer from these conditions. This paper summarizes some aspects of these life-threatening chronic and debilitating diseases that usually require long term specialist care and costly formal and informal surveillance. Epidemiology does have an important role to play in the field of RD, since it provides appropriate methods and tools for assessing exposures and health outcomes.

Increase in motor neuron disease mortality in Spain: temporal and geographical analysis (1990-2005).

The aim of this study was to assess the trend of motor neuron disease mortality in Spain from 1990 to 2005, and to ascertain the existence of geographical differences in mortality rates. MND deaths are registered by the National Statistics Institute of Spain – International Classification of Diseases (ICD) codes ICD9 335.2 (1990-1998) and ICD10 G12.

Osteochondral diseases and fibrodysplasia ossificans progressiva.

Osteochondrodysplasias like thanatophoric dysplasia, osteogenesis imperfecta, achondroplasia, and other genetic skeletal disorders like fibrodysplasia ossificans progressiva are infrequently seen in clinical practice. In cases of sporadic achondroplasia as well as in fibrodysplasia ossificans progressiva, there is a strong association with paternal age, a relationship that is less evident in other genetic osteochondral diseases. No other constitutional or environmental factor has proven to be associated with these disorders.