<p>Hereditary Multiple Exostoses: Current Insights</p>

Abstract

Hereditary multiple exostoses (HME), also called hereditary multiple osteochondromas, is a rare genetic disorder characterized by multiple osteochondromas that grow near the growth plates of bones such as the ribs, pelvis, vertebrae and especially long bones. The disease presents with various clinical manifestations including chronic pain syndromes, restricted range of motion, limb deformity, short stature, scoliosis and neurovascular alteration. Malignant transformation of exostosis is rarely seen. The disease has no medical treatment and surgery is only recommended in symptomatic exostoses or in cases where a malignant transformation is suspected. HME is mainly caused by mutations and functional loss of the EXT1 and EXT2 genes which encode glycosyltransferases, an enzyme family involved in heparan sulfate (HS) synthesis. However, the peculiar molecular mechanism that leads to the structural changes of the cartilage and to osteochondroma formation is still being studied. Basic science studies have recently shown new insights about altering the molecular and cellular mechanism caused by HS deficiency. Pediatricians, geneticists and orthopedic surgeons play an important role in the study and treatment of this severe pathology. Despite the recent significant advances, we still need novel insights to better specify the role of HS in signal transduction. The purpose of this review was to analyze the most relevant aspects of HME from the literature review, give readers an important tool to understand its clinical features and metabolic-pathogenetic mechanism, and to identify an effective treatment method. We focused on the aspects of the disease related to clinical management and surgical treatment in order to give up-to-date information that could be useful for following best clinical practice.

An unusual example of hereditary multiple exostoses: a case report and review of the literature

“…Whilst there are no signs of growths within the hands the medical notes state that tumours in the proximal phalanx of the right 2nd digit were surgically excised 25 years ante-mortem. The literature reports the most affected parts of the skeleton are, in order, the long bones, the scapulae, the ribs, the pelvis and the vertebrae [ 6 ].…”

“…These can either be in the distal femur which occurs 90% of the time [ 2 ], the proximal tibia or proximal fibula which have osteochondromas in 84 and 76% of HME cases respectively [ 2 ]. A third of HME sufferers report genu valgum due to the deformities present at the knee [ 6 ]. As previously noted, this case has osteochondromas in all 3 locations on both lower limbs.…”

“…The complications of the disorder can be severe and vary greatly between individuals reflecting differences of osteochondroma distribution and size. A common theme however is the discomfort experienced by sufferers with 60% of children and 80% of adults experiencing chronic pain [ 6 ].…”

“…HME is an autosomal dominant disease caused by mutations and subsequent loss of function in exostosin (EXT) genes [ 6 ]. Penetrance of 100% is observed in males whilst it is slightly less in females at 96% [ 11 ].…”

EXT1 and EXT2 Variants in 22 Chinese Families With Multiple Osteochondromas: Seven New Variants and Potentiation of Preimplantation Genetic Testing and Prenatal Diagnosis

“…The malformation of legs, forearms and hands is a frequent manifestation ( Matsubara et al, 2006 ). The prevalence of MO is estimated to be 1/50,000 ( Wicklund et al, 1995 ) and would appear to be higher in males (male-to-female ratio, 1.5:1) ( D’Arienzo et al, 2019 ), making it one of the most frequent causes of skeletal dysplasia. MO is characterized by significant inter- and intra-familial phenotypic heterogeneity, including variation in the number and size of osteochondromas, the number and location of the bones involved, and the degree of the deformities arising ( Peterson, 1989 ).…”