The FOP Connection Registry: Design of an international patient-sponsored registry for Fibrodysplasia Ossificans Progressiva.

The Fibrodysplasia Ossificans Progressiva (FOP) Connection Registry is an international, voluntary, observational study that directly captures demographic and disease information initially from patients with FOP (the patient portal) and in the near future from treating physicians (the physician portal) via a secure web-based tool. It was launched by the International FOP Association (IFOPA) with a guiding vision to develop and manage one unified, global, and coordinated Registry allowing the assembly of the most comprehensive data on FOP. This will ultimately facilitate greater access and sharing of patient data and enable better and faster development of therapies and tracking their long-term treatment effectiveness and safety. This report outlines the FOP Connection Registry's design and procedures for data collection and reporting, as well as the long-term sustainability of Registry. Patient-reported, aggregate data are summarized for the first 196 enrolled patients, representing participation from 42 countries and approximately 25% of the world's known FOP population. Fifty-seven percent of the current Registry participants are female with a mean age of 23.8years (median=21years, range=1, 76years). Among the Registry participants who provided their FOP type, 51% reported FOP Classic (R206H), 41% reported FOP Type Unknown, and 8% reported FOP Variant. Patients reported 5.4years (median=3.0years, range=0, 45.8years) as the mean age at which they noticed their first FOP symptoms and a mean age at final FOP diagnosis of 7.5years (median=5.0years, range=0.1, 48.4years). Information on the patients' diagnostic journeys in arriving at a correct diagnosis of FOP is also presented. These early patient-reported data suggest that the IFOPA's vision of one, unified, global, and coordinated approach to the FOP Connection Registry is well underway to being realized. In addition, the positive response from the FOP patient community to the initial launch of the Registry's patient portal has created a solid foundation upon which to build the largest international registry for monitoring the clinical progression of FOP among patients.

Iatrogenic harm caused by diagnostic errors in fibrodysplasia ossificans progressiva.

BACKGROUND: Little is known about diagnostic errors for a disease worldwide. Such errors could alter the disease's natural history, especially if unwarranted interventions cause irreversible harm. Fibrodysplasia ossificans progressiva (FOP), a rare, autosomal dominant genetic disease characterized by episodes of permanent heterotopic ossification of soft tissues, occurs worldwide without racial, ethnic, or geographic predilection. There is no effective treatment, and soft-tissue trauma (eg, biopsies, surgical procedures, intramuscular injections, or mandibular blocks for dental procedures) and viral illnesses are likely to induce episodes of rapidly progressive heterotopic ossification, with resultant permanent loss of motion in the affected area. Accurate diagnoses can be made on the basis of the clinical findings of tumor-like swellings on the head, neck, back, or shoulders and characteristic short great toes with hallux valgus-like malformations and missing interphalangeal joints. On the basis of conversations with numerous individuals with FOP, we suspected that diagnostic errors with FOP are common and often associated with inappropriate and harmful diagnostic and therapeutic procedures. OBJECTIVE: To document the frequency of diagnostic errors with FOP and complications resulting from misdiagnoses. DESIGN: A questionnaire requesting detailed demographic, diagnostic, and treatment information was sent to all 269 patient-members of the International FOP Association; the sampling frame included > 90% of all known FOP patients worldwide. We received 138 replies (51% response) from 25 countries. The age range was 2 to 71 years; there were 78 female subjects and 60 male subjects. In addition, to assess the availability and adequacy of information about FOP, we reviewed 184 English-language textbooks in relevant specialties published in the past 20 years. RESULTS: Incorrect diagnoses were given initially to 87% of individuals with FOP. This astonishing rate of diagnostic errors occurred worldwide, regardless of ethnicity, geographic background, or misdiagnosing physician's specialty. The most common incorrect diagnosis was cancer (32%). The mean period from the onset of symptoms to correct diagnosis was 4.1 years, and the median number of physicians consulted before the correct diagnosis of FOP was 6. For 67% of patients, unnecessary invasive procedures (biopsies) were performed; 68% received inappropriate therapies. Forty-nine percent of all patients reported permanent loss of mobility resulting from invasive medical interventions that caused posttraumatic ossification. Notably, only 8% of the 184 textbooks that were reviewed contained adequate descriptions of FOP, including the caution that trauma can accelerate the process of heterotopic ossification. CONCLUSIONS: Diagnostic errors and inappropriate medical procedures, which may lead to permanent harm, can alter the natural history of a disease. In FOP, the astonishing rates of diagnostic errors and inappropriate invasive medical procedures likely result from lack of physician awareness because of failure of information transfer.

Influenza-like viral illnesses and flare-ups of fibrodysplasia ossificans progressiva.

Flare-ups of fibrodysplasia ossificans progressiva are most commonly triggered by soft tissue trauma. After observing severe flare-ups of fibrodysplasia ossificans progressiva in two half-sisters with culture-confirmed influenza B infections, we hypothesized that influenza-like viral illnesses also can trigger fibrodysplasia ossificans progressiva flare-ups. To address this hypothesis, we designed a questionnaire to assess whether patients with fibrodysplasia ossificans progressiva experienced influenza symptoms during the 2000 to 2001 influenza season, and whether these symptoms were correlated with flare-ups of the condition. The questionnaire was sent to patients with fibrodysplasia ossificans progressiva worldwide. Of the 264 patients surveyed, 123 (47%) responded. The survey revealed that the risk of a disease flare-up of fibrodysplasia ossificans progressiva during an influenza-like viral illness was increased at least threefold and possibly much more. The survey data strongly supported the hypothesis that influenza-like viral illnesses are associated with disease flare-ups in patients who have fibrodysplasia ossificans progressiva. Influenza-like viral illnesses may be a source of previously unrecognized muscle injury leading to heterotopic ossification and permanent loss of mobility in these patients. These findings have important implications for understanding and preventing environmental triggers of disease activity in this population of patients genetically susceptible to progressive heterotopic ossification.