Skip to main content
  • Meeting abstract
  • Open access
  • Published:

Skeletal dysplasias: approach to the clinical diagnosis and implication of appropriate diagnosis for knowledge and research studies in these rare diseases. Hereditary multiple Osteochondromas as example/paradigm

The skeletal dysplasias are a large, heterogeneous group of genetic conditions characterized by abnormal development, growth and maintenance of the elements (bones) comprised in the human skeleton [1]. In the 2010 revision of nosology and classification of genetic skeletal disorders, 456 conditions were included and placed in 40 groups defined by molecular, biochemical, and/or radiographic criteria. Of these conditions, 316 were associated with mutations in one or more of 226 different genes [2], and are present in about 5% of children with birth defects [3]. About 100 skeletal dysplasias have prenatal onset [4] with ultrasound findings particularly in the second trimester [5]. The first step for an accurate diagnosis is a detailed clinical-radiographic evaluation [4]. In fact, because of clinical and genetic heterogeneity of these diseases, with partial clinical overlap, diagnosis is difficult with a consequent delay in specific follow-up and management.

Clinical and molecular characterization of a large patients series is the first step that leads to an improvement in knowledge about natural history, epidemiology and pathogenesis of this disease. These advancements are promoted by expertise centres where patients can be followed-up by multidisciplinary teams, required for syndromic nature or different skeletal segments involvement in the most of cases. To improve skeletal disease knowledge, often lacking, it is essential to analyze and integrate available clinical and genetic data; to this purpose, the design and development of disease-specific registries [5] is essential, as well as the presence of a Biobank for the collection of biospecimens.

Our experience as Reference Centre for Skeletal Dysplasias led us to activate specific diseases registries, as Multiple Osteochondromas Registry (REM), using an HL7 compliant platform, GePhCARD (Genotype-Phenotype Correlation, Analyses and Research Database) that can encompass clinical, genetic, genealogical and imaging data [6]. This web-application is protected by an authentication system, a relief tool articulated in multilevel access profile for data legal protection and patients’ privacy. GePhCARD will be soon interfaced with BIOGEN (Gen etic Bio bank) and together will contribute to improve diagnosis and clinical and molecular characterization of rare diseases, allowing to collect high quality biological materials of skeletal dysplasias patients [7].

In this presentation we focus on our experience on a specific skeletal disease, Hereditary Multiple Osteochondromas (MO), and demonstrate how a systematic integration of clinical and molecular data is focal to increase the knowledge on MO natural history and epidemiology [8], contributing also to define personalized and appropriate follow-up and to hypothesize research studies.


  1. Savarirayan R1, Rimoin DL: The skeletal dysplasias. Best Pract Res Clin Endocrinol Metab. 2002, 16: 547-60. 10.1053/beem.2002.0210.

    Article  PubMed  Google Scholar 

  2. Warman ML1, Cormier-Daire V, Hall C, Krakow D, Lachman R, LeMerrer M, Mortier G, Mundlos S, Nishimura G, Rimoin DL, Robertson S, Savarirayan R, Sillence D, Spranger J, Unger S, Zabel B, Superti-Furga A: Nosology and classification of genetic skeletal disorders: 2010 revision. Am J Med Genet A. 2011, 155A: 943-68. doi: 10.1002/ajmg.a.33909. Epub 2011 Mar 15

    Article  PubMed  Google Scholar 

  3. Orioli IM, Castilla EE, Barbosa-Neto JG: The birth prevalence rates for skeletal dysplasias. J Med Genet. 1986, 23: 328-332. 10.1136/jmg.23.4.328.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Alanay Y, Lachman RS: A review of the principles of radiological assessment of skeletal dysplasias. J Clin Res Pediatr Endocrinol. 2011, 3: 163-78. 10.4274/jcrpe.463.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Parilla BV1, Leeth EA, Kambich MP, Chilis P, MacGregor SN: Antenatal detection of skeletal dysplasias. J Ultrasound Med. 2003, 22: 255-8. quiz 259-61

    PubMed  Google Scholar 

  6. 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, 161: 556-60. 10.1002/ajmg.a.35819.

    Article  CAS  Google Scholar 

  7. Brand AM1, Probst-Hensch NM: Biobanking for epidemiological research and public health. Pathobiology. 2007, 74: 227-38. 10.1159/000104450.

    Article  PubMed  Google Scholar 

  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, 93: 2294-302.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations


Rights and permissions

Open Access  This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

To view a copy of this licence, visit

The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gnoli, M., Pedrini, E., Mordenti, M. et al. Skeletal dysplasias: approach to the clinical diagnosis and implication of appropriate diagnosis for knowledge and research studies in these rare diseases. Hereditary multiple Osteochondromas as example/paradigm. Ital J Pediatr 40 (Suppl 1), A8 (2014).

Download citation

  • Published:

  • DOI: