Clinical and Genetic Analysis of Multiple Osteochondromas in A Cohort of Argentine Patients

Genes (Basel). 2022 Nov 7;13(11):2063. doi: 10.3390/genes13112063.


Multiple Osteochondromatosis (MO, MIM 133700 & 133701), an autosomal dominant O-glycosylation disorder (EXT1/EXT2-CDG), can be associated with a reduction in skeletal growth, bony deformity, restricted joint motion, shortened stature and pathogenic variants in two tumor suppressor genes, EXT1 and EXT2. In this work, we report a cross-sectional study including 35 index patients and 20 affected family members. Clinical phenotyping of all 55 affected cases was obtained, but genetic studies were performed only in 35 indexes. Of these, a total of 40% (n = 14) had a family history of MO. Clinical severity scores were class I in 34% (n:18), class II in 24.5% (n:13) and class III in 41.5% (n:22). Pathogenic variants were identified in 83% (29/35) probands. We detected 18 (62%) in EXT1 and 11 (38%) in EXT2. Patients with EXT1 variants showed a height z-score of 1.03 SD lower than those with EXT2 variants and greater clinical severity (II-III vs. I). Interestingly, three patients showed intellectual impairment, two patients showed a dual diagnosis, one Turner Syndrome and one hypochondroplasia. This study improves knowledge of MO, reporting new pathogenic variants and forwarding the worldwide collaboration necessary to promote the inclusion of patients into future biologically based therapeutics.

Keywords: EXT1/EXT2-CDG; O-glycosylation disorders; multiple exostosis; multiple osteochondromatosis; osteochondroma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cross-Sectional Studies
  • Exostoses, Multiple Hereditary* / diagnosis
  • Exostoses, Multiple Hereditary* / genetics
  • Genetic Testing
  • Humans
  • Mutation
  • N-Acetylglucosaminyltransferases / genetics


  • N-Acetylglucosaminyltransferases

Grants and funding

The authors are also grateful for the support from the Scientific and Technical National Research Council (PIP CONICET 11220170100790CO); BID No. 2437 OC-AR PICT2010-2824), Catholic University of Cordoba and a Garrahan Hospital Foundation Grant. This work was also supported in part by the following research grants awarded to KEH (SAF2017-84646-R and PID2020-116263RB-I00 from the Ministerio de Economia, Industria y Competividad, and co-funded by the “Fondo Europeo de Desarrollo Regional” (FEDER)).