Hereditary Multiple Exostoses (HME) (also called Hereditary Multiple Osteochondromas) is a rare genetic condition characterized by growths of multiple benign cartilage-capped bone tumors that grow outward from the metaphysis of the long bones (Wuyts et al., 2000). These exostoses/osteochondromas can result in shortened stature, limb length discrepancy, restricted joint mobility, and nerve compression or pain. Ulnar lengthening surgeries are often performed, but the optimal timing and value of this surgery is debated by orthopedic experts and there is limited evidence of long-term benefit (El-Sobky et al., 2018). Osteochondromas are associated with a 2-5% risk of malignancy; this risk increases with age, and is more common in males and those with EXT1 pathogenic/likely pathogenic (P/LP) variants. (Phan et al., 2017, Fei et al., 2018). 

The diagnosis of HME is primarily made through clinical evaluation and x-ray. Individuals with the condition present with multiple osteochondromas from the growth plate in the juxtaphyseal region of long bones or from the surface of flat bones (Wuyts et al., 2000). Nearly all affected individuals receive a diagnosis by age 12 years, with the majority showing symptoms before age 3 years. Inheritance is autosomal dominant, with nearly complete penetrance. Most individuals inherit HME from a parent, but about 10% of cases are due to de novo P/LP variants (Wuyts et al., 2000). 

There are 2 genes associated with HME: EXT1 and EXT2. The disease is part of a group of congenital disorders of glycosylation and therefore, an alternate name for this disorder is EXT1/EXT2-CDG (Serra-Vinardell et al., 2019). P/LP variants in EXT1 account for 56-78% of HME cases, while EXT2 P/LP variants have been found in 20-40% of affected individuals. Deletions and duplications have been reported for both genes. There have been some reports of specific differences in the anatomical distribution of lesions based on the causative gene (Fusco et al., 2019). Confirmatory genetic testing for EXT1 and EXT2 is not always necessary, as a clinical diagnosis is readily made in most affected individuals. Testing may be indicated for those patients in whom a diagnosis is uncertain, as the risk of malignancy associated with osteochondromas warrants surveillance (Jamsheer et al., 2014; Jennes et al., 2009). Since clinical diagnosis is apparent at an early age, presymptomatic testing of family members is typically not warranted. However, genetic testing for the purpose of prenatal testing and/or reproductive decision making may be desired by some patients.