Height, Ulnar Length and Forearm Function in Multiple Hereditary Exostoses

Exostoses, Multiple Hereditary Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05914298
• Other study ID #: 0012479
• Status: Completed
• Start date: January 1, 2018
• Est. completion date: February 1, 2022

Study information

• Verified date: June 2023
• Source: Istituto Ortopedico Rizzoli
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 408
• Est. completion date: February 1, 2022
• Est. primary completion date: February 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Exostoses, Multiple Hereditary

Intervention

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
• PUL
measurement of ulnar length with anthropometer and patient's height
• Range of motion
measurement of range of motion of elbow, forearm and wrist

Locations

Country	Name	City	State
Italy	Manila Boarini	Bologna

Sponsors (1)

Lead Sponsor	Collaborator
Istituto Ortopedico Rizzoli

Country where clinical trial is conducted

Italy, 

References & Publications (4)

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. — View Citation

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 201 — View Citation

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: 10.10 — View Citation

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	proportional ulnar length (PUL)	proportional ulnar length (PUL) is the ratio between ulnar lenght and the height of the patient	1 year
Secondary	genotype	identify potential association among the genotypic pattern (EXT1 or EXT2) and phenotypic presentation	1 year
Secondary	forearm function	elbow, forearm and wrist range of motion (ROM) measured by a goneometer	1 year
Secondary	EuroQol 5D	EQ-5D is a standardised measure of health-related quality of life developed by the EuroQol Group	1 year

External Links

•   Rizzoli Orthopaedic Institute