The Italian National Registry for FSHD: an enhanced data integration and an analytics framework towards Smart Health Care and Precision Medicine for a rare disease

Abstract

Background The Italian Clinical network for FSHD (ICNF) has established the Italian National Registry for FSHD (INRF), collecting data from patients affected by Facioscapulohumeral dystrophy (FSHD) and their relatives. The INRF has gathered data from molecular analysis, clinical evaluation, anamnestic information, and family history from more than 3500 participants. Methods A data management framework, called Mediator Environment for Multiple Information Sources (MOMIS) FSHD Web Platform, has been developed to provide charts, maps and search tools customized for specific needs. Patients’ samples and their clinical information derives from the Italian Clinical network for FSHD (ICNF), a consortium consisting of fourteen neuromuscular clinics distributed across Italy. The tools used to collect, integrate, and visualize clinical, molecular and natural history information about patients affected by FSHD and their relatives are described. Results The INRF collected the molecular data regarding FSHD diagnosis conducted on 7197 subjects and identified 3362 individuals carrying a D4Z4 Reduced Allele (DRA): 1634 were unrelated index cases. In 1032 cases the molecular testing has been extended to 3747 relatives, 1728 carrying a DRA. Since 2009 molecular analysis has been accompanied by clinical evaluation based standardized evaluation protocols. In the period 2009–2020, 3577 clinical forms have been collected, 2059 follow the Comprehensive Clinical Evaluation form (CCEF). The integration of standardized clinical information and molecular data has made possible to demonstrate the wide phenotypic variability of FSHD. The MOMIS (Mediator Environment for Multiple Information Sources) data integration framework allowed performing genotype–phenotype correlation studies, and generated information of medical importance either for clinical practice or genetic counseling. Conclusion The platform implemented for the FSHD Registry data collection based on OpenClinica meets the requirement to integrate patient/disease information, as well as the need to adapt dynamically to security and privacy concerns. Our results indicate that the quality of data collection in a multi-integrated approach is fundamental for clinical and epidemiological research in a rare disease and may have great value in allowing us to redefine diagnostic criteria and disease markers for FSHD. By extending the use of the MOMIS data integration framework to other countries and the longitudinal systematic collection of standardized clinical data will facilitate the understanding of disease natural history and offer valuable inputs towards trial readiness. This approach is of high significance to FSHD medical community and also to rare disease research in general.

Update on the Molecular Aspects and Methods Underlying the Complex Architecture of FSHD

“…Facioscapulohumeral muscular dystrophy (FSHD) represents the third most common dystrophy, affecting 1:8333 individuals worldwide. The disease is generally characterized by a progressive weakness involving the muscles of the face and the upper and lower extremities [ 1 , 2 , 3 ], although a wide range of mild-to-severe phenotypes are observed [ 4 ]. Moreover, extra-muscular phenotypes are known, such as hearing loss and retinal vascular pathologies.…”

Scoping review of the recommendations and guidance for improving the quality of rare disease registries

“…Data ownership and data custodianship are at the forefront of data governance [ 16 , 35 , 36 , 38 , 48 , 59 ]. Data ownership refers to the possession, responsibility, and control of data including the right to assign access privileges to others [ 60 ].…”

“…A registry might also benefit from designated data entry personnel who can systematically monitor and evaluate data quality [ 38 ]. A Support Team or Help Desk is also beneficial to the operations of the registry [ 59 ].…”

“…FAIR data principles stand for Findability (easy to find for both humans and computers), Accessibility (easily retrievable and accessible by users), Interoperability (easily integrates with other data), and Reusability (well-described so it can be replicated or applied in another setting). Since FAIR principles enable the extensive and efficient use of registry data while mitigating duplication, recollection, and errors [ 25 , 56 ], it is recommended that the registry data infrastructure complies with FAIR principles [ 18 , 25 , 26 , 37 , 38 , 59 , 75 , 83 , 84 ].…”

“…Regardless of the methods used to collect, store, and manage data sets, data encryption and firewalling of servers are standard [ 59 , 63 ]. The encryption of data while in transit is an added layer of data security [ 27 , 32 , 40 ].…”