REGISTRY OF DRAVET SYNDROME AND OTHER SYNDROMES
CORRELATED WITH GENE SCN1A AND PCDH19 MUTATION
Mutations of the SCN1A and PCDH19 genes present themselves clinically with a wide spectrum of variation and severity, most often characterised by a frequent recurrence of seizures, both febrile and non-febrile. These seizures are principally characterised by being worsened by a fever. Patients presenting with the mutation or deletion of the PCDH19 gene can experience both febrile and non-febrile seizures from an early age but further develop in a different way comparing to those with Dravet Syndrome.
Dravet Syndrome begins in the first year of life with convulsive seizures, often prolonged, and in particular accompanied by the fever, in babies who were up until then considered healthy. Over time, delays in psychomotor development, behaviour and attention disorders are often present in patients with Dravet syndrome. Other patients bearing this gene mutation develop less serious forms of epilepsy and are less neurologically compromised, or they can simply present occasional seizures throughout their lives, without any sign of impaired cognitive function. The evolution into the more serious or less serious forms cannot be predicted easily based on the mutation type. This can lead to anxiety in the family of an affected person for whom, after the initial presentation of the epileptic seizures precipitated by fever, a genetic test reveals a mutation on one of these genes. At the same time, the referred specialist may be indecisive on which therapeutic strategy to adopt to reduce the frequency of the epileptic seizures. To address this issue, the Registry considers all these factors, and is known as the Registro della Sindrome di Dravet e altre Sindromi correlate a mutazioni dei geni SCN1A e PCDH19 (Registry of Dravet Syndrome and other Syndromes Correlated with Gene SCN1and PCDH19 Mutation), or more simply RE.SI.DRA.S.
The creation of the registry of diseases has been supported by Associazione Dravet Italia Onlus (https://www.dravet.it and works alongside the Scientific Medical Committee (https://www.dravet.it/about and the Fondazione Toscana “Gabriele Monasterio”, Pisa (which manages the information of the registry), with the remit to create a bank of usable data and to promote the research on these epileptic syndromes, in support of a better program of care pathways. The data collected in the registry will therefore be accessible, subjected to current privacy legislation, to those who request properly documented health or scientific projects which the scientific committee considers to be of tangibile benefit to the knowledge and treatment of the disease.
The availability of reliable statistical data throughout is a key element in enabling understanding of related phenomena in the distribution of a disease. The Registry of Pathology is able to provide specific epidemiological data relative to specific pathologies, and to fulfil their function they have to be able to count on the collaboration of all the structures that operate nationally, and find a central coordinating point from which to collect data to manage the flow of information. The particular design of the registry brings to light a greater number of cases, of the specific causative genetic anomaly, of their inclusion in one of the diverse treatments, allowing us to follow the evolution of those treatments over time and to chart any emergent complications or comorbidity factors that can affect the outcome of the patient. A registry, depending on the type of information collected, may be able to provide others with classic epidemiological data like rate of incidents, measurement of prevalence, mortality rates, survival rates etc., measurement of clinical performance, until you obtain an improvement in the quality of treatment and in the outcomes of patients, and to define, in large numbers, correlations between genotypes and phenotypes, which will be useful for the purpose of planning more targeted therapeutic strategies.
The Registry of Dravet Syndrome and other Syndromes Correlated with Gene SCN1A and PCDH19 Mutation collects personal, clinical, pharmacological and genetic data from the patients and proposes to include centres which deal with diagnosis and with the care of this pathology in their networks. During the initial pilot phase the Registry RESIDRAS will be supported by pitot Italian the following centres:
Neurologia Pediatrica AOU Meyer (Firenze), Istituto Neurologico C.Besta (Milano), Università degli Studi di Padova, IRCCS Stella Maris (Pisa), Policlinico Gemelli (Roma), AOUI di Verona.
Each centre has been identified by Associazione Dravet Italia Onlus. After the initial pilot phase of the registry, which will help identify any potential improvements to avoid any loss of information, all the national centres validated by the Scientific Medical Committee will be involved.
Due to the positive experience, Dravet Italia Onlus promoted an international registry called “Platform-RESIDRAS”. These two registries have the same data set, but two different Coordinating Committee.
The pilot phase of Platform-Residras involved following pilot centres: UMC Utrecht/SEIN, Netherlands; University Hospital Antwerp, Belgium; Filadelfia, Denmark; UCL - Institute of Child Health - Clinical Neurosciences, United Kingdom; and Hôpital Necker-Enfants Malades - Service de Neurologie - Epilepsies Rares - CHU Paris, France. The international registry is now also open to all centres that request their participation in this project.