Height, Ulnar Length and Forearm Function in Multiple Hereditary Exostoses

Analysis of the Relationship Among Height, Ulnar Length and Forearm Function in Patients With Multiple Hereditary Exostoses and Association With the Genotypic Pattern

the purpose of the present registry is to describe the epidemiology of forearm deformities in patients with Hereditary Multiple Exostoses and to identify, independent predictors of severity of the disease and potential association with genotypic patterns

Study Overview

• Status: Completed
• Conditions: Exostoses, Multiple Hereditary
• Intervention / Treatment: Diagnostic test: blood and buccal swab genetic test; Diagnostic test: PUL; Diagnostic test: Range of motion

Detailed Description

Hereditary Multiple Exostoses (HME) is a rare pediatric autosomal dominant disorder caused by loss-of-function mutations in the genes encoding the heparan sulfate (HS)-synthesizing enzymes EXT1 or EXT2. HME affects 1 in 50,000 people and has 100% penetrance but great variability in phenotypic expression. HME is characterized by formation of cartilaginous outgrowths, called osteochondromas or exostoses, next to the growth plates of many axial and appendicular skeletal elements, causing multiple, painful disfiguring and disabling skeletal deformities, and potential malignant transformation into peripherral chondrosarcoma.

The involvement of upper-limb bones by HME is associated with greater loss of function than elsewhere in the body, but even here the loss of function may be limited. Moreover, the constant relationship between height and ulnar length has long been recognized in forensic medicine and has been recently analyzed also in HME, in order to predict the clinical and functional outcomes of the upper limb.

the present registry aims to collect demographic, clinical, functional and radiographic information from patients with HME in order to establish phenotypic predictors of severity of the disease and potential association with genotypic patterns

• Study Type: Observational
• Enrollment (Actual): 408

Contacts and Locations

Study Locations

• Italy
  • Bologna, Italy, 40136
    • Manila Boarini

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Children and adults Patients with HME.

Description

Inclusion Criteria:

- patients with HME (> 2 exostoses)

Exclusion Criteria:

• Patients with solitary exostoses
• Patients, adults or minors, who are unable to give their timely informed consent.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HME group; 204 children and adult patients with HME, admitted to our Hospital for diagnosis and treatment. the patients will be stratified by age in four subgroups: subgroup I (0-7 Years); subgroup II (8-12 Years); subgroup III (13-18 Years); subgroup IV (>18 Years)	Diagnostic test: blood and buccal swab genetic test; blood samples and buccal swabs will be obtained from patients with HME in order to analyze the genotype (EXT1 or EXT2 mutations) and correlate the genotypic pattern with the phenotypic presentation; Diagnostic test: PUL; measurement of ulnar length with anthropometer and patient's height; Diagnostic test: Range of motion; measurement of range of motion of elbow, forearm and wrist
healty control group; 204 children and adult voluntary healty controls will be stratified in the same manner and matched with the population in study in order to assess normal and pathologic growth.	Diagnostic test: PUL; measurement of ulnar length with anthropometer and patient's height; Diagnostic test: Range of motion; measurement of range of motion of elbow, forearm and wrist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proportional ulnar length (PUL)	proportional ulnar length (PUL) is the ratio between ulnar lenght and the height of the patient	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
genotype	identify potential association among the genotypic pattern (EXT1 or EXT2) and phenotypic presentation	1 year
forearm function	elbow, forearm and wrist range of motion (ROM) measured by a goneometer	1 year
EuroQol 5D	EQ-5D is a standardised measure of health-related quality of life developed by the EuroQol Group	1 year

Collaborators and Investigators

• Sponsor: Istituto Ortopedico Rizzoli
• Investigators: Principal Investigator: Giovanni Luigi Di Gennaro, MD, Istituto Ortopedico Rizzoli

Publications and helpful links

General Publications

• Pedrini E, De Luca A, Valente EM, Maini V, Capponcelli S, Mordenti M, Mingarelli R, Sangiorgi L, Dallapiccola B. Novel EXT1 and EXT2 mutations identified by DHPLC in Italian patients with multiple osteochondromas. Hum Mutat. 2005 Sep;26(3):280. doi: 10.1002/humu.9359.
• 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.
• Clement ND, Porter DE. Forearm deformity in patients with hereditary multiple exostoses: factors associated with range of motion and radial head dislocation. J Bone Joint Surg Am. 2013 Sep 4;95(17):1586-92. doi: 10.2106/JBJS.L.00736.

Helpful Links

• Rizzoli Orthopaedic Institute

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Actual): February 1, 2021
• Study Completion (Actual): February 1, 2022

Study Registration Dates

• First Submitted: January 16, 2018
• First Submitted That Met QC Criteria: June 21, 2023
• First Posted (Actual): June 22, 2023

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 21, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Multiple Hereditary Exostoses, forearm, height, ulnar length
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Genetic Diseases, Inborn; Musculoskeletal Diseases; Bone Diseases; Neoplastic Syndromes, Hereditary; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Bone Diseases, Developmental; Osteochondrodysplasias; Hyperostosis; Osteochondroma; Exostoses, Multiple Hereditary; Osteochondromatosis; Exostoses; Osteophyte
• Other Study ID Numbers: 0012479

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No