Editing Hereditary multiple exostoses (section)

== Presentation ==
A noticeable lump in relation to an [[limb (anatomy)|extremity]] may be the first presenting symptom. Multiple deformities can arise, namely coronal plane deformities around the knees, ankles, shoulders, elbows, and wrists. For example, ''genu valgum'' (knock knees), ankle valgus, ulnar bowing and shortening, and radial head subluxation are encountered. The majority of affected individuals have clinically manifest osteochondromas around the knee. Forearm involvement in  HMO is considerable.<ref name=elsobky2018/><ref name=Alvarez2007>{{cite journal | vauthors = Alvarez CM, De Vera MA, Heslip TR, Casey B | title = Evaluation of the anatomic burden of patients with hereditary multiple exostoses | journal = Clinical Orthopaedics and Related Research | volume = 462 | pages = 73–79 | date = September 2007 | pmid = 17589361 | doi = 10.1097/BLO.0b013e3181334b51 | s2cid = 39999620 }}</ref> Intra-articular osteochondromas of the hip can induce  limitation of range of motion, joint pain and acetabular dysplasia.<ref name="refmakhdom" /> Likewise joint pain at other locations and neurovascular compression can occur. Furthermore, functional disability in regard to activities of daily living can be a presenting feature. Spinal deformity pain or neurological compromise should arouse suspicion of  involvement of the vertebrae.<ref name="Genereviews" /><ref>{{Cite journal |last=Monroig-Rivera |first=Carlos |last2=Bockhorn |first2=Lauren |last3=Thornberg |first3=David |last4=Santillan |first4=Brenda |last5=Rathjen |first5=Karl E. |date=January–March 2025 |title=Prevalence of Osteochondromas in the Spine in Patients with Multiple Hereditary Exostoses |url=https://journals.lww.com/jbjsoa/fulltext/2025/03000/prevalence_of_osteochondromas_in_the_spine_in.27.aspx |journal=JB & JS Open Access |language=en-US |volume=10 |issue=1 |pages=e24.00072 |doi=10.2106/JBJS.OA.24.00072 |issn=2472-7245|pmc=11905973 }}</ref> Furthermore, short stature may occur and is generally disproportionate. Such manifestations usually result from disruption of physeal growth especially that osteochondromas typically arise at the metaphyseal ends of long bones in close proximity to the physis.<ref name=elsobky2018/><ref name=Alvarez2007/>

=== Pain ===
According to self-reports, a far majority of patients experience pain, and about half experience generalized pain. Individuals who had HME-related complications were five times more likely to have pain, while those who had surgery were 3.8 times more likely to have pain. No differences were found between males and females with respect to pain, surgery, or HME-related complications.<ref>{{cite journal | vauthors = Darilek S, Wicklund C, Novy D, Scott A, Gambello M, Johnston D, Hecht J | title = Hereditary multiple exostosis and pain | journal = Journal of Pediatric Orthopedics | volume = 25 | issue = 3 | pages = 369–376 | date = May 2005 | pmid = 15832158 | doi = 10.1097/01.bpo.0000150813.18673.ad | s2cid = 27884079 }}</ref>

=== Possible connection to autism ===
Some parents of children with HME have observed [[autism]]-like social problems in their children. To explore those observations more deeply, a 2012 study by the [[Sanford-Burnham Medical Research Institute]] used a mouse model of HME to observe cognitive function. The findings indicated that the mutant mice endorsed three autistic characteristics: social impairment, impairments in [[ultrasonic vocalization]], and repetitive behavior.<ref>{{cite journal | vauthors = Irie F, Badie-Mahdavi H, Yamaguchi Y | title = Autism-like socio-communicative deficits and stereotypies in mice lacking heparan sulfate | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 13 | pages = 5052–5056 | date = March 2012 | pmid = 22411800 | pmc = 3323986 | doi = 10.1073/pnas.1117881109 | doi-access = free | bibcode = 2012PNAS..109.5052I }}</ref>

=== Heparan sulfate connections ===
MHE stems from an inability to biosynthesize [[heparan sulfate]], a proteoglycan. As Cuellar et al. note: "[E]ncoding glycosyltransferases involved in the biosynthesis of ubiquitously expressed heparan sulphate (HS) chains, are associated with MHE."<ref>{{cite journal | vauthors = Cuellar A, Reddi AH | title = Cell biology of osteochondromas: bone morphogenic protein signalling and heparan sulphates | journal = International Orthopaedics | volume = 37 | issue = 8 | pages = 1591–1596 | date = August 2013 | pmid = 23771188 | pmc = 3728397 | doi = 10.1007/s00264-013-1906-5 }}</ref><ref>{{cite journal | vauthors = Jones KB, Pacifici M, Hilton MJ | title = Multiple hereditary exostoses (MHE): elucidating the pathogenesis of a rare skeletal disorder through interdisciplinary research | journal = Connective Tissue Research | volume = 55 | issue = 2 | pages = 80–88 | date = April 2014 | pmid = 24409815 | doi = 10.3109/03008207.2013.867957 }}</ref>