Dataset Information

The Rizzoli Multiple Osteochondromas Classification revised: describing the phenotype to improve clinical practice.

ABSTRACT: Multiple osteochondromas (MO) is a rare disorder, characterized by benign osteocartilaginous tumors (osteochondromas), arising from the perichondrium of bones. The osteochondromas increase during growth, frequently causing deformities and limitations. Our study aims to analyze the data captured by the Registry of Multiple Osteochondromas, to refine Istituto Ortopedico Rizzoli (IOR) Classification, providing a representative picture of the phenotypic manifestations throughout the lifespan. We conducted a single-institution cross-sectional study. Patients were categorized according to IOR Classification, which identifies three patients' classes on the presence/absence of deformities and/or limitations. The present dataset was compared with our previously published data, to refine the classification. Nine hundred sixty-eight patients were included: 243 children (<10 years), 136 adolescents (10-15 years), and 589 adults. Of the entire population, half patients presented at least one deformity, and one quarter reported at least one limitation. Compared with our previous study, the amount of children was more than doubled and the percentage of mild/moderate cases was notably increased, giving a better disease overview throughout the lifespan and suggesting a different cut-off for dividing Class II in subclasses. We confirmed that MO is characterized by phenotypic heterogeneity, suggesting that an early classification of the disease may offer a useful tool to follow disease pattern and evolution, to support clinical practice, and to propose timely interventions.

SUBMITTER: Mordenti M

PROVIDER: S-EPMC9293117 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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The Rizzoli Multiple Osteochondromas Classification revised: describing the phenotype to improve clinical practice.

Mordenti Marina M Gnoli Maria M Boarini Manila M Trisolino Giovanni G Evangelista Andrea A Pedrini Elena E Corsini Serena S Tremosini Morena M Staals Eric L EL Antonioli Diego D Stilli Stefano S Donati Davide M DM Sangiorgi Luca L

American journal of medical genetics. Part A 20210903 11

Multiple osteochondromas (MO) is a rare disorder, characterized by benign osteocartilaginous tumors (osteochondromas), arising from the perichondrium of bones. The osteochondromas increase during growth, frequently causing deformities and limitations. Our study aims to analyze the data captured by the Registry of Multiple Osteochondromas, to refine Istituto Ortopedico Rizzoli (IOR) Classification, providing a representative picture of the phenotypic manifestations throughout the lifespan. We con ...[more]

PMID: 34477285

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Project description:Multiple osteochondromas (MO) is characterised by development of two or more cartilage capped bony outgrowths (osteochondromas) of the long bones. The prevalence is estimated at 1:50,000, and it seems to be higher in males (male-to-female ratio 1.5:1). Osteochondromas develop and increase in size in the first decade of life, ceasing to grow when the growth plates close at puberty. They are pedunculated or sessile (broad base) and can vary widely in size. The number of osteochondromas may vary significantly within and between families, the mean number of locations is 15-18. The majority are asymptomatic and located in bones that develop from cartilage, especially the long bones of the extremities, predominantly around the knee. The facial bones are not affected. Osteochondromas may cause pain, functional problems and deformities, especially of the forearm, that may be reason for surgical removal. The most important complication is malignant transformation of osteochondroma towards secondary peripheral chondrosarcoma, which is estimated to occur in 0.5-5%. MO is an autosomal dominant disorder and is genetically heterogeneous. In almost 90% of MO patients germline mutations in the tumour suppressor genes EXT1 or EXT2 are found. The EXT genes encode glycosyltransferases, catalyzing heparan sulphate polymerization. The diagnosis is based on radiological and clinical documentation, supplemented with, if available, histological evaluation of osteochondromas. If the exact mutation is known antenatal diagnosis is technically possible. MO should be distinguished from metachondromatosis, dysplasia epiphysealis hemimelica and Ollier disease. Osteochondromas are benign lesions and do not affect life expectancy. Management includes removal of osteochondromas when they give complaints. Removed osteochondromas should be examined for malignant transformation towards secondary peripheral chondrosarcoma. Patients should be well instructed and regular follow-up for early detection of malignancy seems justified. For secondary peripheral chondrosarcoma, en-bloc resection of the lesion and its pseudocapsule with tumour-free margins, preferably in a bone tumour referral centre, should be performed.

Project description:Multiple Osteochondromas (MO; previously known as multiple hereditary exostosis) is an autosomal dominant genetic condition that is characterized by the formation of cartilaginous bone tumours (osteochondromas) at multiple sites in the skeleton, secondary bursa formation and impingement of nerves, tendons and vessels, bone curving, and short stature. MO is also known to be associated with arthritis, general pain, scarring and occasional malignant transformation of osteochondroma into secondary peripheral chondrosarcoma. MO patients present additional complains but the relevance of those in relation to the syndromal background needs validation. Mutations in two enzymes that are required during heparan sulphate synthesis (EXT1 or EXT2) are known to cause MO. Previously, we have used zebrafish which harbour mutations in ext2 as a model for MO and shown that ext2⁻/⁻ fish have skeletal defects that resemble those seen in osteochondromas. Here we analyse dental defects present in ext2⁻/⁻ fish. Histological analysis reveals that ext2⁻/⁻ fish have very severe defects associated with the formation and the morphology of teeth. At 5 days post fertilization 100% of ext2⁻/⁻ fish have a single tooth at the end of the 5(th) pharyngeal arch, whereas wild-type fish develop three teeth, located in the middle of the pharyngeal arch. ext2⁻/⁻ teeth have abnormal morphology (they were shorter and thicker than in the WT) and patchy ossification at the tooth base. Deformities such as split crowns and enamel lesions were found in 20% of ext2⁺/⁻ adults. The tooth morphology in ext2⁻/⁻ was partially rescued by FGF8 administered locally (bead implants). Our findings from zebrafish model were validated in a dental survey that was conducted with assistance of the MHE Research Foundation. The presence of the malformed and/or displaced teeth with abnormal enamel was declared by half of the respondents indicating that MO might indeed be also associated with dental problems.

Dataset Information

The Rizzoli Multiple Osteochondromas Classification revised: describing the phenotype to improve clinical practice.

Publications

The Rizzoli Multiple Osteochondromas Classification revised: describing the phenotype to improve clinical practice.

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