Clinical trial NCT05914298: Height, Ulnar Length and Forearm Function in Multiple Hereditary Exostoses
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Exostoses, Multiple Hereditary
Keywords: Multiple Hereditary Exostoses, forearm, height, ulnar length
Lead sponsor: Istituto Ortopedico Rizzoli
Sponsor class: OTHER
First posted: 2023-06-22
Enrollment: 408
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Children and adults Patients with HME.

Brief 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

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

Eligibility criteria: 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.

Primary outcomes:
measure: proportional ulnar length (PUL)
timeFrame: 1 year
Secondary outcomes:
measure: genotype
timeFrame: 1 year
measure: forearm function
timeFrame: 1 year
measure: EuroQol 5D
timeFrame: 1 year
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: Manila Boarini
Study officials:
affiliation: Istituto Ortopedico Rizzoli
name: Giovanni Luigi Di Gennaro, MD
role: PRINCIPAL_INVESTIGATOR
References:
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: 10.1002/humu.9359.
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 2013 Feb 8.
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 "protective" and "risk" factors. J Bone Joint Surg Am. 2011 Dec 21;93(24):2294-302. doi: 10.2106/JBJS.J.00949.
citation: 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.