Multiple Hereditary Exostosis

Key Points:

  • Characterized by multiple osteochondromas, metaphyseal in origin, confluent with the intra-medullary space
  • Autosomal dominant inheritance caused by mutations in the EXT1, EXT2, and EXT3 (tumor suppressor genes)
  • 1-5% chance of malignant transformation to chondrosarcoma 

Description:

  Hereditary multiple exostosis is a benign disorder characterized by multiple chondrogenic lesions (osteochondromas) found on the surfaces of bones, often at the sites of tendon insertions. They are most commonly found in the proximal femur, distal femur, proximal tibia, and the proximal humerus.

Epidemiology:

  MHE has an estimated prevalence of 0.9-2 / 100,000 in Caucasians. The true prevalence is unknown as many patients with a mild phenotype may not be diagnosed (Stieber, 2005).

Clinical Findings:

  These chondrogenic lesions are most commonly located in the metaphysis of long bones but may also be found on the vertebral borders of the scapulae, iliac crests, and ribs (Stieber, 2005).  MHE is diagnosed in the first decade of life in 80% of patients. The lesions are often first identified in the tibia or scapula due to their superficial location (Stieber, 2005).  Occasionally, MHE will be diagnosed at birth when the infant’s parents are also found to have the disease (Stieber, 2005).  

  Symptoms associated with MHE include prominence in superficial locations, painful snapping of muscle or tendon over an exostosis, short stature, limb length discrepancy, valgus deformity of the knee or ankle, and deformity of the forearm with associated radial head subluxation and loss of forearm rotation (Stieber, 2005).  Clinical exam will detect firm, non-mobile masses in the appendicular skeleton.  Range of motion of adjacent joints should be assessed.  Extra-canal spine lesions may present with dysphagia or sleep apnea, while intra-canal spine lesions may cause pain, headaches, dizziness, weakness, paresthesias, gait disturbance, or other neurologic symptoms (Ashraf, 2013).

Imaging Studies:

  Radiographs reveal either sessile or pedunculated lesions found on the surface of bones. Sessile lesions have a broad base, contiguous with the cortex of the bone. Pedunculated lesions have a tapered stalk connected to a larger lesion. These lesions are often directed away from the physis. The cortex of the lesion is always continuous with the cortex of the native bone. The medullary cavity is continuous with the medullary cavity of the bone. Some lesions can be followed clinically if the patient is mimimally symptomatic.  When there is involvement of the hip, knee, ankle, or forearms, more frequent radiographic evaluation may be important to assess for progressive malalignment.  Development of a painful lesion is an indication for obtaining radiographs.

  MRI can be used to better characterize the lesion. The cartilage cap that cannot be seen on plain films will be seen on MRI. Increasing cartilage cap thickness raises concern for possible malignant transformation, particularly greater than 20 mm.  Some authors have recommend a screening total spine MRI during childhood to evaluate for the presence of an intra-canal exostosis.

Etiology:

MHE is caused by autosomal dominant inheritance of mutations in genes EXT1, EXT2, and EXT3. Half of all cases of MHE are caused by a mutation in EXT1 on 8q24.1. Mutations of EXT2 on 11p13 can be found in 1/3 of MHE. EXT 2 has a higher rate of malignant transformation and greater number of exostoses (Schmale, 1994).  The EXT genes encode exostosins, which are involved in the formation of heparin sulfate and help regulate chondrocyte maturation within the growth plate (Pannier, 2008).  Affected individuals have a 50% risk of transmitting the disorder to their children.

Treatment:

  Most patients do not require treatment prior to reaching skeletal maturity and remain asymptomatic throughout life. Some patients do become symptomatic when the lesions cause pain and inflammation to the surrounding tissue. Surgical excision is recommended in symptomatic lesions. The base of stalk along with the cartilaginous cap should be excised.  Patients with MHE are at risk for joint malalignment.  Lesions of the proximal femur and pelvis can cause deformity and subluxation of the hip joint.  Distal tibia lesions can cause syndesmosis widening or angular deformity.  Deformities of the distal forearm may develop due to radius or ulna lesions.  Surgical excision of lesions and guided growth procedures can be performed to improve joint alignment, particularly in the knee and ankle region.

Complications:

  Recurrence of an exostosis is rare after surgical excision but may occur due to incomplete removal of a lesion in continuity with the physis or incomplete removal of a cartilaginous cap (Chin, 2000).iiThere is a 1% risk of malignant transformation to chondrosarcoma in patients with a solitary osteochondroma. Patients with MHE have an approximately 1-5% risk of exostosis transformation to chondrosarcoma. A cartilage cap greater than 20 mm has been associated with increased risk of malignancy.  Symptoms of malignant transformation may include pain and increase in size of an exostosis after skeletal maturity (Stieber, 2005).

References:

  1. Ashraf A, Larson AN, Ferski G, Mielke CH, Wetjen NM, Guidera KJ. Spinal stenosis frequent in children with multiple hereditary exostoses. J Child Orthop. 2013 Jun;7(3):183-94. 
  2. Chin KR, Kharrazi FD, Miller BS, Mankin HJ, Gebhardt MC: Osteochondromas of thedistal aspect of the tibia or fibula: Natural history and treatment. J Bone Joint Surg Am. 2000;82:1269-1278.
  3. Pannier S, Legeai-Mallet L. Hereditary multiple exostoses and enchondromatosis. BestPract Res Clin Rheumatol. 2008 Mar;22(1):45-54.
  4. Roach JW, Klatt JW, Faulkner ND.  Involvement of the spine in patients with multiplehereditary exostoses. J Bone Joint Surg Am. 2009;91(8):1942-8.
  5. Rupprecht M, et.al.  Rebound of ankle valgus deformity in patients with hereditarymultiple exostosis. J Pediatr Orthop  2015 January; 1: 94-99
  6. Schmale GA, Conrad EU III, Raskind WH: The natural history of hereditary multipleexostoses. J Bone Joint Surg Am. 1994;76:986-992.
  7. Stieber JR, Dormans JP. Manifestations of hereditary multiple exostoses. J Am AcadOrthop Surg. 2005 Mar-Apr;13(2):110-20.
  8. Thompson RL1, Hosseinzadeh P, Muchow RD, Talwalkar VR, Iwinski HJ, Walker JL, 
  9. Milbrandt TA. Syringomyelia and vertebral osteochondromas in patients with multiple hereditary exostosis. J Pediatr Orthop B. 2014 Sep;23(5):449-53.

Top Contributors:

Andres Chen MD
Janay Mckie MD