Registry of Multiple Osteochondromas (REM)

Registry of Multiple Osteochondromas That Collects Clinical, Functional, Genetic, Genealogical, Imaging, Surgical, Treatment, Quality of Life Data. Data is Linked to Patients' Biological Samples, When Available.

REM is a retrospective and prospective registry, finalized for care and research purposes. It is articulated in main sections - strongly related and mutually dependent on each other - corresponding to different data domains: personal information, clinical data, genetic data, genealogical data, surgeries, etc.

This approach has been developed to corroborate and integrate data from different sources evaluating several aspects of diseases and to correlate genetic background and phenotypic outcomes, in order to better investigate disease pathophysiology. Due to legal requirements, institutional directives and organizational issues, we are unable to include individuals residing outside Italy in the registry at this time. We are currently engaged in the preparation of a recruitment process for individuals residing outside Italy.

Study Overview

• Status: Recruiting
• Conditions: Multiple Osteochondromas

Detailed Description

The traditional method of collecting patient information is often chaotic, inconvenient, and sometimes even unsafe, particularly when dealing with rare diseases. In 2013, the need to simplify the diagnostic process and to overcome the difficulties of data storage and analysis, led to the suggestion of implementing the Registry of Multiple Osteochondromas (REM).

The REM relies on an IT platform named Genotype-phenotype Data Integration platform - GeDI. This solution was developed through a collaboration between Rare Skeletal Disease Department and a local software company (Dilaxia S.p.A.) and is General Data Protection Regulation (GDPR)-compliant, multi-client and web-accessible. It has been designed according to current medical informatics standards, including the Orphanet code, the International Classification of Diseases (ICD), and the Human Genome Variants Society, aiming to follow Findability, Accessibility, Interoperability, Reusability (FAIR) principles. GeDI is continuously being implemented to improve the management of people with Multiple Osteochondromas and to assist researchers in analyzing the information collected. REM is divided into the following main sections:

• Personal data: it comprises general information, birth details and residence data;
• Patient data: including the patients internal code, the hospital code and other patient details;
• Diagnostic Process: the diagnosis, the status (affected, suspected, etc.), age at diagnosis, comorbidities, allergies, etc.;
• Genogram: a tool for designing the family transmission of the disease, alongside information on the disease status of all relatives included;
• Clinical events: it records a long list of signs and symptoms of Multiple Osteochondromas as well as several additional items to describe the disease
• Genetic Analysis and Alteration: including analytical technique, sample information, analysis duration, etc. This section also comprises detailed information on any detected pathological variants (e.g. gene, international reference, DNA change, protein change, genomic position, etc.);
• Visits: this section includes visit type (genetic, orthopedic, rehabilitation, pediatric, etc.), the date of the visit, prescriptions, imaging, etc.;
• Treatments: this section comprises information of a wide range of treatments including pharmacological, devices, supplements, and other treatments such as psychological, nutritional, etc;
• Surgeries: this section contains information on the type of surgeries, the age of the patients, the site/localization of the procedures, etc.
• Documents: this repository allow us to store all types of documents (radiological reports, imaging, consents, clinical reports, etc.);
• Consents: this section provides a comprehensive overview of all consents collected, including the collection date;
• Samples: this section includes information on the samples, like the type, date of collection, etc.
• PROs: this section collects information on patients reported outcomes such as the quality of life or ABC scale.

• Study Type: Observational
• Enrollment (Estimated): 10000

Contacts and Locations

• Study Contact: Name: Marina Mordenti, PhD; Phone Number: +39 05 6366062; Email: registri.malattierare@ior.it
• Study Contact Backup: Name: Marcella Lanza, MSc; Phone Number: +39 05 6366169; Email: registri.malattierare@ior.it

Study Locations

• Italy
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40136
      • Recruiting
      • IRCCS Istituto Ortopedico Rizzoli
      • Contact: Marina Mordenti, PhD; Phone Number: +39 051 6366062; Email: registri.malattierare@ior.it
      • Contact: Marcella Lanza, PhD; Phone Number: +39 051 6366169; Email: registri.malattierare@ior.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Patients affected by Multiple Osteochondromas. The Registry will include also data on fetuses (prenatal).

Description

Inclusion Criteria:

• All Multiple Osteochondromas patients, including prenatal diagnosis of Multiple Osteochondromas

Exclusion Criteria:

• Any condition unrelated to Multiple Osteochondromas

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Multiple Osteochondromas patients; Patients affected by Multiple Osteochondromas. The Registry will include also data on fetuses (prenatal).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Natural History and Epidemiology in terms of clinical, genetic and functional evaluation	To maintain an established registry in order to assess epidemiology and natural history. Collection of: physical examinations data: assessment of severity of the disease (according to Mordenti et al classification); orthopedic and functional data: stature (cm), weight (kg), number and localization of sites affected, site of malignant transformation, definition of deformities (localization and number), definition of limitations (localization and number); surgical procedures: type, number and site of surgeries disease-related and age at surgeries; genetics background: target gene, type of mutation, type of variant detected, clinical significance; family history: inheritance; treatment information: pharmacological, devices, supplements, and other treatments All the features are updated at each follow up. Clinical reports, medical charts, genetic report and imaging are the primary sources of data	25 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genotype-Phenotype Correlation among clinical features and molecular background	The secondary outcome comprises the correlation between genotype and phenotype. This includes but is not limited to clinical features and genetic background. This will be pursued using the information collected during visits and follow-ups and the genetic information resulting from molecular investigations.	25 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Longitudinal study of disease evolution (including prospective and retrospective data)	This outcome aims to investigate the evolution of Multiple Osteochondromas during time. This will be evaluated within the families and among the families. Main clinical features, such as height (cm), number and localization of osteochondromas, number and localization of deformities, number and localization of limitations will be collected both retrospectively and prospectively in the entire population, with a particular attention to the pediatric population. Primarily in adult population, disease evolution is focused on malignant transformation. An evaluation of these parameters will be performed at each visit to keep track on the progression of clinical manifestations.	25 years

Collaborators and Investigators

• Sponsor: Luca Sangiorgi
• Investigators: Principal Investigator: Luca Sangiorgi, MD, PhD, MS, Istituto Ortopedico Rizzoli

Publications and helpful links

General Publications

• Mordenti M, Ferrari E, Pedrini E, Fabbri N, Campanacci L, Muselli M, Sangiorgi L. Validation of a new multiple osteochondromas classification through Switching Neural Networks. Am J Med Genet A. 2013 Mar;161A(3):556-60. doi: 10.1002/ajmg.a.35819. Epub 2013 Feb 8.
• Pedrini E, Jennes I, Tremosini M, Milanesi A, Mordenti M, Parra A, Sgariglia F, Zuntini M, Campanacci L, Fabbri N, Pignotti E, Wuyts W, Sangiorgi L. Genotype-phenotype correlation study in 529 patients with multiple hereditary exostoses: identification of "protective" and "risk" factors. J Bone Joint Surg Am. 2011 Dec 21;93(24):2294-302. doi: 10.2106/JBJS.J.00949.
• Schmale GA, Conrad EU 3rd, Raskind WH. The natural history of hereditary multiple exostoses. J Bone Joint Surg Am. 1994 Jul;76(7):986-92. doi: 10.2106/00004623-199407000-00005.
• Pacifici M. Hereditary Multiple Exostoses: New Insights into Pathogenesis, Clinical Complications, and Potential Treatments. Curr Osteoporos Rep. 2017 Jun;15(3):142-152. doi: 10.1007/s11914-017-0355-2.
• Vink GR, White SJ, Gabelic S, Hogendoorn PC, Breuning MH, Bakker E. Mutation screening of EXT1 and EXT2 by direct sequence analysis and MLPA in patients with multiple osteochondromas: splice site mutations and exonic deletions account for more than half of the mutations. Eur J Hum Genet. 2005 Apr;13(4):470-4. doi: 10.1038/sj.ejhg.5201343.
• White SJ, Vink GR, Kriek M, Wuyts W, Schouten J, Bakker B, Breuning MH, den Dunnen JT. Two-color multiplex ligation-dependent probe amplification: detecting genomic rearrangements in hereditary multiple exostoses. Hum Mutat. 2004 Jul;24(1):86-92. doi: 10.1002/humu.20054.
• Wuyts W, Van Hul W. Molecular basis of multiple exostoses: mutations in the EXT1 and EXT2 genes. Hum Mutat. 2000;15(3):220-7. doi: 10.1002/(SICI)1098-1004(200003)15:33.0.CO;2-K.
• Darilek S, Wicklund C, Novy D, Scott A, Gambello M, Johnston D, Hecht J. Hereditary multiple exostosis and pain. J Pediatr Orthop. 2005 May-Jun;25(3):369-76. doi: 10.1097/01.bpo.0000150813.18673.ad.
• Cacciari E, Milani S, Balsamo A, Spada E, Bona G, Cavallo L, Cerutti F, Gargantini L, Greggio N, Tonini G, Cicognani A. Italian cross-sectional growth charts for height, weight and BMI (2 to 20 yr). J Endocrinol Invest. 2006 Jul-Aug;29(7):581-93. doi: 10.1007/BF03344156.
• Cacciari E, Milani S, Balsamo A, Dammacco F, De Luca F, Chiarelli F, Pasquino AM, Tonini G, Vanelli M. Italian cross-sectional growth charts for height, weight and BMI (6-20 y). Eur J Clin Nutr. 2002 Feb;56(2):171-80. doi: 10.1038/sj.ejcn.1601314.
• Porter DE, Lonie L, Fraser M, Dobson-Stone C, Porter JR, Monaco AP, Simpson AH. Severity of disease and risk of malignant change in hereditary multiple exostoses. A genotype-phenotype study. J Bone Joint Surg Br. 2004 Sep;86(7):1041-6. doi: 10.1302/0301-620x.86b7.14815.
• Goud AL, de Lange J, Scholtes VA, Bulstra SK, Ham SJ. Pain, physical and social functioning, and quality of life in individuals with multiple hereditary exostoses in The Netherlands: a national cohort study. J Bone Joint Surg Am. 2012 Jun 6;94(11):1013-20. doi: 10.2106/JBJS.K.00406.
• D'Ambrosi R, Ragone V, Caldarini C, Serra N, Usuelli FG, Facchini RM. The impact of hereditary multiple exostoses on quality of life, satisfaction, global health status, and pain. Arch Orthop Trauma Surg. 2017 Feb;137(2):209-215. doi: 10.1007/s00402-016-2608-4. Epub 2016 Dec 8.

Helpful Links

• Institutional webpage of Registries For Rare Hereditary Diseases

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2013
• Primary Completion (Actual): July 1, 2018
• Study Completion (Estimated): December 1, 2032

Study Registration Dates

• First Submitted: October 14, 2019
• First Submitted That Met QC Criteria: October 17, 2019
• First Posted (Actual): October 21, 2019

Study Record Updates

• Last Update Posted (Actual): November 20, 2025
• Last Update Submitted That Met QC Criteria: November 17, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Natural History Study; Disease Registry; Genotype-Phenotype Correlation; Disease evolution
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Neoplasms; Genetic Diseases, Inborn; Neoplasms by Histologic Type; Neoplastic Syndromes, Hereditary; Neoplasms, Connective and Soft Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Osteochondrodysplasias; Bone Diseases, Developmental; Exostoses; Hyperostosis; Osteochondroma; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Osteochondromatosis; Exostoses, Multiple Hereditary
• Other Study ID Numbers: 21629/2013

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No