Symptoms and General Pathology

All Conditions

Neoplasms

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Rare Diseases

Syndrome

Li-Fraumeni Syndrome

Neoplastic Syndromes, Hereditary

Genetic Diseases, Inborn

DNA Repair-Deficiency Disorders

Metabolic Diseases

The group comprises all patients affected by Li Fraumeni and Li Fraumeni Like syndromes

Luca Sangiorgi, MD, PhD

Marina Mordenti, PhD

Manila Boarini, MSc

Luca Sangiorgi, MSc

ReLF is a retrospective and prospective registry, finalized to care and research. 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 individuated in order to corroborate and integrate data from different resources and aspects of the diseases and to correlate genetic background and phenotypic outcomes, in order to better investigate diseases pathophysiology.

The common way to collect patient information is frequently chaotic and inconvenient (sometimes even unsafe), particularly when dealing with rare diseases. The need to simplify the diagnostic process and to overcome the difficulties of data storage and analysis, suggested in 2020 to implement the Registry of Li Fraumeni and Li Fraumeni Like syndromes (ReLF)

The ReLFrelies on an IT Platform named GeDI (Genotype-phenotype Data Integration platform). This solution, realized by a collaboration among Department of Rare Skeletal Disorders and a local software-house (NSI - Nier IT Solution), is a GDPR-compliant, multi-client, web-accessible system and it has been designed according to current medical informatics standards (Orphacode, ICD-10, Human Genome Variants Society, Findability Accessibility Interoperability Reusability -FAIR- Principles). GeDI is continuously implemented to improve management of persons with Osteogenesis Imperfecta and to help researchers in analysing collected information. ROI is articulated in main sections:

Ø Personal data: it comprises general information, birth details and residence data Ø Patient data: including the patients internal code, the hospital code and other details on patients Ø Diagnosis: the diagnosis, the status (affected, suspect, etc.), age at diagnosis, comorbidities, allergies, etc.

Ø Genogram: a tool to design family transmission of the disease, flanked by info on diseases status of all included relatives.

Ø Clinical events: records several signs and symptoms of Li Fraumeni and Li Fraumeni like syndromes (representing the main disease features) and 12 additional items to describe the disease Ø Genetic Analysis and Alteration: including technique, sample information, duration of analysis, etc. In addition, this section comprises detailed information on detected pathological variants (gene, international reference, DNA change, Protein change, genomic position, etc.).

Ø Visits: it includes the typology of the visit (genetic, orthopaedic, rehabilitation, paediatric, etc.), the date of the visit, treatment, prescription, imaging, etc.

Ø Surgeries: this section contains information on the surgeries type, the age of the patients, the site/localization of the procedures, etc.

Ø Documents: this repository is allowed to store all type of documents (radiological reports, imaging, consents, clinical reports, etc.).

Ø Consents: this section comprises a complete overview of all collected consents, including the date of collection.

Ø Samples: it comprises the type of samples (DNA, tissue, whole peripheral blood, etc.)

Registry of Li Fraumeni and Li Fraumeni Like Syndromes

Registry of Li Fraumeni and Li Fraumeni Like Syndromes - Registro Della Sindrome di Li Fraumeni Classica e Li Fraumeni Like

This outcome aims to investigate similarities and difference of tumoral manifestation (site of the tumor, type of tumor, age at onset, grade of leasion) in patients affected by Li Fraumeni or Li Fraumeni Like syndromes within the families and among the families.

Assessment of epidemiological information (incidence, prevalence measured as percentages and/or ratios).

Anthropometric data: weight in kg, height in cm. In addition, weight and height will be combined to report BMI as kg/m\^2 Clinical details of the tumor: site of the lesion, number of recurrence(s), presence/absence of metastasis, size of lesion in cm\^3 Additional clinical data: type of surgery, age at surgery in years are updated at each follow up and retrospectively (when possible).

Clinical reports, medical charts and imaging are the primary source of data.

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.

Collection of genetics background (target gene, type of mutation, clinical significance are reported following HGVS nomenclature) and family history (in terms of inheritance by maternal or paternal line).

Anthropometric data (weight in kg, height in cm. In addition, weight and height will be combined to report BMI in kg/m\^2), clinical details (site of the lesion, recurrence, metastasis), orthopaedic and functional features are updated at each follow up.

Istituto Ortopedico Rizzoli

Head of Department of Rare Skeletal Disorders

Musculoskeletal Diseases

Skin and Connective Tissue Diseases

Behaviors and Mental Disorders

Osteochondroma

Exostoses, Multiple Hereditary

Osteochondromatosis

Exostoses

Osteophyte

Enchondromatosis

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Osteochondrodysplasias

Mucopolysaccharidosis IV

Bone Diseases

Bone Diseases, Developmental

Hyperostosis

Quality of Life

Hereditary Multiple Osteochondromas

Ollier Disease

Mucopolysaccharidosis Type IV

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

Luca Sangiorgi, MD, PhD, MS

REM is a retrospective and prospective registry, finalized to care and research. 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 individuated in order to corroborate and integrate data from different resources and aspects of the diseases and to correlate genetic background and phenotypic outcomes, in order to better investigate diseases pathophysiology.

The common way to collect patient information is frequently chaotic and inconvenient (sometimes even unsafe), particularly when dealing with rare diseases. The need to simplify the diagnostic process and to overcome the difficulties of data storage and analysis, suggested in 2013 to implement the Registry of Multiple Osteochondromas (REM).

The REM relies on an IT Platform named Genotype-phenotype Data Integration platform -GeDI.This solution, realized by a collaboration among Medical Genetic Department and a local software-house (NSI - Nier IT Solution), is a General Data Protection Regulation (GDPR)-compliant, multi-client, web-accessible system and it has been designed according to current medical informatics standards (Orphanet code, ICD-10, Human Genome Variants Society, Findability Accessibility Interoperability Reusability Principles). GeDI is continuously implemented to improve management of persons with Multiple Osteochodromas and to help researchers in analysing collected information. REM is articulated in 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 details on patients
* Diagnosis: the diagnosis, the status (affected, suspect, etc.), age at diagnosis, comorbidities, allergies, etc.
* Genogram: a tool to design family transmission of the disease, flanked by info on diseases status of all included relatives
* Clinical events: records more than 20 signs and symptoms of Multiple Osteochondromas and 12 additional items to describe the disease
* Genetic Analysis and Alteration: including technique, sample information, duration of analysis, etc. In addition, this section comprises detailed information on detected pathological variants (gene, international reference, DNA change, Protein change, genomic position, etc.)
* Visits: it includes the typology of the visit (genetic, orthopaedic, rehabilitation, paediatric, etc.), the date of the visit, treatment, prescription, imaging, etc.
* Surgeries: this section contains information on the surgeries type, the age of the patients, the site/localization of the procedures, etc.
* Documents: this repository is allowed to store all type of documents (radiological reports, imaging, consents, clinical reports, etc.)
* Consents: this section comprises a complete overview of all collected consents, including the date of collection.
* Samples: it comprises the type of samples (DNA, tissue, whole peripheral blood, etc.)

Whole peripheral blood, DNA, lymphocytes, cartilage tissues, bone tissues

Registry of Multiple Osteonchodromas

Registry of Multiple Osteochondromas That Collects Clinical, Functional, Genetic, Genealogical, Imaging, Surgical, Quality of Life Data. Data Are Linked to Patients Biological Sample

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 for paediatric population. An evaluation of these parameters will be performed at each visit to keep trace on the progression of the clinical manifestations.

In adult population, the disease evolution is centered on malignant transformation.

To maintain an established registry in order to assess epidemiology and natural history (such as incidence, prevalence, etc.) of Multiple Osteochondromas.

Collection of:

1. physical examinations data: assessment of severity of the disease (defined according to Mordenti et al classification)
2. orthopaedic and functional data: stature (cm), weight (kg), number and localization of sites affected by osteochondromas, site of malignant transformation, definition of deformities (localization and number), definition of limitations (localization and number)
3. surgical procedures: type, number and site of surgeries disease-related and age at surgeries
4. genetics background: target gene, type of mutation, type of variant detected, clinical significance
5. family history: inheritance in maternal or paternal line

Clinical, orthopaedic and functional features are updated at each follow up. Clinical reports, medical charts, genetic report and imaging are the primary source of data.

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.

Luca Sangiorgi

Head of Departement of Rare Skeletal Disorders

Maffucci Syndrome

The group comprises all patients affected by Ollier Disease and Maffucci Syndrome.

The common way to collect patient information is frequently chaotic and inconvenient (sometimes even unsafe), particularly when dealing with rare diseases. The need to simplify the diagnostic process and to overcome the difficulties of data storage and analysis, suggested in 2013 to implement the Registry of Ollier Disease and Maffucci Syndrome (ROM).

The ROM relies on an IT Platform named Genotype-phenotype Data Integration platform -GeDI.This solution, realized by a collaboration among Medical Genetic Department and a local software-house (NSI - Nier IT Solution), is a General Data Protection Regulation (GDPR)-compliant, multi-client, web-accessible system and it has been designed according to current medical informatics standards (Orphanet code, ICD-10, Human Genome Variants Society, Findability Accessibility Interoperability Reusability Principles). GeDI is continuously implemented to improve management of persons with Ollier Disease and Maffucci Syndrome and to help researchers in analysing collected information. ROM is articulated in 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 details on patients Diagnosis: the diagnosis, the status (affected, suspect, etc.), age at diagnosis, comorbidities, allergies, etc.

Genogram: a tool to design family transmission of the disease, flanked by info on diseases status of all included relatives Clinical events: records 23 signs and symptoms of Ollier Disease and Maffucci Syndrome and 12 additional items to describe the disease Genetic Analysis and Alteration: including technique, sample information, duration of analysis, etc. In addition, this section comprises detailed information on detected pathological variants (gene, international reference, DNA change, Protein change, genomic position, etc.) Visits: it includes the typology of the visit (genetic, orthopaedic, rehabilitation, paediatric, etc.), the date of the visit, treatment, prescription, imaging, etc.

Surgeries: this section contains information on the surgeries type, the age of the patients, the site/localization of the procedures, etc.

Documents: this repository is allowed to store all type of documents (radiological reports, imaging, consents, clinical reports, etc.) Consents: this section comprises a complete overview of all collected consents, including the date of collection.

Samples: it comprises the type of samples (DNA, tissue, whole peripheral blood, etc.)

Whole peripheral blood, DNA, lymphocytes, tissues

Registry of Ollier Disease and Maffucci Syndrome

Registry of Ollier Disease and Maffucci Syndrome That Collects Clinical, Functional, Genetic, Genealogical, Imaging, Surgical, Quality of Life Data. Data Are Linked to Patients Biological Sample

This outcome aims to investigate the evolution of Ollier Disease and Maffucci Syndrome during time.

Main clinical features evaluated:

* Height (cm) age-related (compared to growth chart)
* Number and localization of enchondromas
* Number and localization of deformities
* Number and localization of functional limitations
* Site at malignant transformation (adult)
* Age at malignant transformation (adult)

Number: count of enchondromas, deformities, etc. Localization: defined using bone affected, site (proximal, distal, etc.) and side (left, right, both)

Those data will be collected both retrospectively and prospectively for all patients via physical examination, clinical reports and imaging.

An evaluation of these parameters will be performed at each visit to keep trace on the progression of the clinical manifestations. Data will be collected to define annualized rate of new clinical manifestations related to age, using analyses such as Kaplan-Meyer and surviving rate.

To maintain an established registry in order to assess epidemiology and natural history (such as incidence, prevalence, etc.).

Collection of:

1. Physical examinations data:

   * BMI (kg/m\^2)
   * Number and localization of sites affected by enchondromas
   * Presence/absence of angiomas
   * Localization and number of deformities
   * Localization and number of functional limitations
2. Surgical procedures disease-related:

   * Type of surgeries
   * Number of surgeries
   * Site of surgeries
   * Age at surgeries
3. Genetics background: studies of somatic variants
4. Family history: anamnestic family information

Number: count of enchondromas, deformities, etc. Localization: defined using bone affected, site (proximal, distal, etc.) and side (left, right, both)

Clinical, orthopaedic and functional features are updated at each follow up. Clinical reports, medical charts and imaging are the primary source of data.

Despite the unclear genetic background of Ollier disease and Maffucci syndrome, the secondary outcome aims to correlate 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.

Study title	NCT ID	Conditions	Eligibility	Organization
Registry of Li Fraumeni and Li Fraumeni Like Syndromes	NCT04982744	Li-Fraumeni Syn... Li-Fraumeni-Lik...	-	Istituto Ortopedico Rizzoli
Registry of Multiple Osteonchodromas	NCT04133285	Multiple Osteoc...	-	Istituto Ortopedico Rizzoli
Registry of Ollier Disease and Maffucci Syndrome	NCT04134572	Ollier Disease Maffucci Syndro...	-	Istituto Ortopedico Rizzoli
Registry of Li Fraumeni and Li Fraumeni Like Syndromes	NCT04982744	Li-Fraumeni Syn... Li-Fraumeni-Lik...	-	Istituto Ortopedico Rizzoli

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