Printer Friendly

Multiple skeletal deformities in a middle-aged man.

A 54-year-old man was seen in our endocrinology clinic with evidence of a limited range of motion in his left foot. He had a history of diabetes mellitus type 2 and atrial fibrillation. His family history included evidence of skeletal deformities in some of his relatives. This could imply the potential existence of a hereditary condition. It is worth noting that spontaneous mutations have been reported in some cases. A pertinent physical examination revealed a surgical scar on the patient's left knee, a hallux valgus deformity on his left foot with compromised joint function, and painless bony prominences on that same foot. The skeletal survey findings were consistent with multiple hereditary exostoses. Multiple osteochondromatosis (MO) is a rare genetic disorder associated with serious complications that may significantly affect the health-related quality of life of anyone having the disorder. To prevent further complications, these patients require long-term follow-up with regular clinical and radiological examinations.

Key words: Multiple Osteochondromatosis (MO), Hereditary Multiple Exostoses (HME), Chondrosarcoma, Exostosin Genes

Paciente masculino de 54 anos de edad evaluado en las clinicas de endocrinologia por limitacion al movimiento del pie izquierdo. Presentaba historial de diabetes tipo 2 y fibrilacion atrial. Algunos de sus parientes presentaban deformidades oseas, lo cual pudiese implicar la posibilidad de una condicion hereditaria. Sin embargo se han reportado mutaciones espontaneas en algunos casos. El examen fisico pertinente demostro una cicatriz quirurgica en su rodilla izquierda, deformidad de hallux valgus y anomalias esqueleticas no dolorosas del pie izquierdo. Los hallazgos en radiografias oseas fueron consistentes con exostosis multiple hereditaria. Esta condicion es un desorden genetico poco comun asociado con complicaciones que pueden afectar significativamente la calidad de vida de estos pacientes. Por esta razon es recomendable ofrecer seguimiento a largo plazo con examenes fisicos y radiografias frecuentes para prevenir serias complicaciones.


Multiple osteochondromatosis (MO), also known as hereditary multiple exostoses (HME), is a rare genetic disorder with an estimated prevalence of 1/50,000 among US adults (l). It seems to be more prevalent in males than in females (male-to-female ratio of 1.5:1) (2). It is an autosomal dominant condition caused by mutations of 2 exostosin genes: EXT 1 and EXT 2. EXT1 and EXT2, located, respectively, at 8q24 and 111p11-pl2, have been implicated as the cause of MO (2). An additional linkage to chromosome 19p has been found, suggesting the existence of an EXT3 gene. The EXT genes encode glycosyltransferases, catalyzing heparan sulfate polymerization (2). Mutations in EXT 1 or EXT2 result in multiple benign cartilaginous capped lesions growing in the juxtaphyseal region (l). They are either pedunculated or sessile (broad based) and can vary widely in size.

Although 90% of all individuals with HME have an affected parent, 10% have a de novo mutation (2). The diagnosis of MO is based on clinical and/or radiographic findings of multiple exostoses in 1 or more members of the family (3). Sequence and deletion analysis of the entire coding region of these genes may provide a prenatal diagnosis for those fetuses that are at increased risk and provide, as well, an opportunity for genetic counseling. Although exostoses are benign lesions, they are often associated with characteristic progressive skeletal deformities and may cause clinical symptoms with serious complications.

Case History

A 54-year-old man seen at the endocrinology clinic with evidence of multiple skeletal deformities. The patient had a past medical history of diabetes mellitus type II, diagnosed 18 years prior, dyslipidemia, arterial hypertension, atrial fibrillation, and osteoarthritis. There was a family history of diabetes mellitus type II (his mother) and lung cancer (his father), as well as skeletal prominences (his great uncle and that uncle's son). At age 17 the patient underwent a surgical procedure of his left knee because of a limb-length discrepancy. A physical examination yielded the following data: height, 72 inches, weight, 115 kg, and evidence of a slight limp. His left foot had a hallux valgus deformity with compromised joint motion due to non-tender prominent bony masses but without erythema, swelling, increased skin temperature, or regional lymphadenopathy (Figure l). The patient has had these skeletal prominences since childhood. No evidence of any hemangiomas or neurofibromas was apparent. Cutaneous sensation was assessed with a monofilament; this assessment revealed the presence of diabetic neuropathy with intact pulses. The patient reported having no history of fractures, pain, nerve-related symptoms, or increases in the size of his current bony prominences. His physical function and quality of life were generally well preserved. Because Charcot joint or Paget's disease was suspected, laboratories and a skeletal survey were ordered. Blood cell count, alkaline phosphatase, 25-OH vitamin D3, ionized calcium, and phosphorus were within normal limits. A skeletal survey showed multiple broad-based cortical protuberances on the left foot and ankle, with extensive osseous deformity consistent with sessile exostoses. Similar findings were present on the left hand, first digit, and on the medial aspect of the left distal femur and on the medial tibial plateau. No evidence of malignant transformation or nerve impingement was observed. Meniscal chondrocalcinosis and bowing of the left fibula were also noted (Figure 2). A wholebody scan revealed focal skeletal abnormalities and an increased concentration of radiotracer in the left sternoclavicular region, left medial femoral condyle, left ankle, and left foot, which increased concentration is consistent with the diagnosis of multiple metabolically active exostoses.


Osteochondromas may cause pain and a reduction in skeletal growth, bony deformity, restricted joint motion, shortened stature, premature osteoarthrosis, and the compression of peripheral nerves. The median age at diagnosis is 3 years; nearly all affected individuals are diagnosed by age 12 (3). Osteochondromas form predominantly on the physes of the long bones, pelvis, ribs, scapula, and vertebrae and begin to appear as early as 2 years of age (4).

MO patients have a lower health-related quality of life than does the general population (l). MO patients suffer more pain and undergo more surgeries compared to the general population. Osteochondromas are removed only when they cause pain, when they are the source of functional complaints (the compression of nerves or vessels), or for cosmetic reasons (3).

Often, associated with relative shortening and bowing of the ulna and fibula, wrist and ankle deformities are observed. Also, distal radioulnar, tibio-fibular diastasis, tapering and tilt of the tibial epiphyses and distal radius could be present. This condition can be treated effectively by combining hemiphyseal stapling of the distal radius and tibia with ulnar and fibular lengthening (5). Limb length discrepancies greater than 1 inch are treated with epiphysiodesis (growth plate arrest) of the longer leg; early treatment of ankle deformities may prevent further deterioration of function.

The most dreaded of all the complications is the malignant transformation to secondary chondrosarcoma, which occurs in 0.5 to 5% of all cases. The clinical signs of this malignant transformation include a sudden increase in the size of the tumor after puberty accompanied by pain. An increase in the thickness of the cartilaginous cap of more than 1 cm (visible on an x-ray) should raise the suspicion of chondrosarcoma (6). When malignancy occurs, satisfactory results are obtained by undergoing an en-bloc resection of the lesion and its pseudocapsule with tumor-free margins, best done in a bone tumor referral center. Usually this procedure renders good long-term clinical results (2).

The differential diagnosis of hereditary multiple exostoses includes the enchondromatosis, which are a heterogeneous group of syndromes that present with multiple enchondromas associated with pathological fractures, pseudarthrosis, limb shortening, malignant transformation risk, and scoliosis. Enchondromatosis, such as Ollier disease, present as asymmetric intraosseous benign cartilaginous tumors, which are usually not the result of an inherited disorder (7). Other differential diagnoses of bone tumors are mentioned in Table 1.

In patients with multiple family members with bone tumors, obtaining a careful history and doing a physical examination are crucial for suspected MO. Our patient declined genetic counseling and refused, as well, to undergo any surgery related to correcting his left ankle deformity. He presented with orthopedic deformities early in life, for which he underwent left knee surgery. He has remained stable over time, without significant complications.

A high level of suspicion is important in patients having a family history of bone tumors and osteochondroma visible in plain x-rays. These patients may benefit from genetic testing as well as from being counseled to seek medical attention; to avoid further complications if their conditions changes. Changes could be manifested as pain, and increase in size of existing lesions.

It must be noted that eventually the majority of these cases will end up undergoing reconstructive surgery and single or multiple joint replacement (knee, hip and ankle).

Early diagnosis of this condition will not only prevent the burden to society that will be caused by the many patients who will end up becoming incapacitated because of their physical problems, but will also further prevent the need for lifelong treatments to maintain the quality of life of these patients.

Although there is good literature review published regarding cases of hereditary multiple exostoses, however, only a few cases have been reported in Puerto Rico. We believe that our case will alert the medical profession to the importance of recognizing this disorder early so as to avoid its long-term consequences.


(1.) Chhina H, Davis JC, Alvarez CM. Health-related Quality of Life in People with Hereditary Multiple Exostoses. J Pediatr Orthop 2012;32:210-214.

(2.) Bovee J VMG. Multiple osteochondromas. Orphanet J Rare Dis. 2008; 3:3. Available at: Url: http://www.ojrd.eom/content/3/l/3. Accessed March 3, 2013.

(3.) Schmale GA, Wuyts W, Chansky HA, Raskind WH. Hereditary Multiple Osteochondromas. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong CT, Smith RJH, Stephens K, eds. Gene Reviews. [Internet]. Seattle (WA): University of Washington, Seattle, WA; 1993-2014. August 3, 2000 [updated 2008, Sep 5]. Available at: Url: http://www.

(4.) Roehl HH, Pacifici M. Shop Talk: Sugars, Bones, and a Disease Called Multiple Hereditary Exostoses. Dev Dyn 2010;239:1901-1904.

(5.) Peterson HA. Multiple Hereditary Osteochondromata. Clin Orthop Relat Res 1989;(239):222-230.

(6.) Anantharamaiah H, Kalyani R, Harendra Kumar ML, Manohar PV. Secondary Chondrosarcoma of the Lumbosacral Region: Are any Bones Spared in the Multiple Hereditary Exostoses? J Clin Diagn Res 2012;6:1778-1780.

(7.) Munoz J, Guo Y. Familial History of Bone Tumors. JAMA 2012; 308: 1476-1477. Available at: Url: aspx?articleid= 1377899. Accessed March 31,2013.

Jose Hernan Martinez-Mendez, MD, FACP *; Madeleine Gutierrez-Acevedo, MD (†); Angel A. Gomez-Cintron, MD, MPH ([double dagger]); Michelle Mangual-Garcia, MD (†); Alfredo Sanchez-Cruz, MD (†); Rafael Trinidad-Hernandez, MD (†); Monica Santiago-Nunez, MD (†); Carlos Figueroa-Nunez, MD (†); Maria de Lourdes Miranda-Adorno, MD (§); Coromoto Palermo-Garofalo, MD (†); Oberto Torres-Rafael, MD (†)

* Endocrinology and Metabolism Program Director, (†) Endocrinology Department, San Juan City Hospital, San Juan, PR; ([double dagger]) Musculoskeletal Radiology, Radiology Department, University of Puerto Rico Medical Sciences Campus, San Juan, PR; (§) Internal Medicine Program Director, Endocrinology Department, San Juan City Hospital, San Juan, PR

The authors have no conflicts of interest to disclose.

Address correspondence to: Jose Hernan Martinez-Mendez, MD, FACP, Endocrinology and Metabolism Program Director, Endocrinology Department, San Juan City Hospital, San Juan, PR 00921. Email:

Table 1. Differential diagnosis of bone tumors

Bone Tumor              Age                   Common Location

Periosteal chondroma    Children and Adults   Proximal humerus,

                        M>F 2:1               proximal and distal

                                              femur, and the

                                              phalanges of the hands

                                              and feet.

Osteochondroma/MHE      Apparent within the   Distal femur, proximal

                        first 12 years of     tibia, pelvis, and

                        life. M>F 1.5:1       metaphyseal ends of the

                                              bones near the joint.

Non-ossifying fibroma   Children              Juxtaepiphysealregion

                        75% occur in the      of the long bones.

                        second decade.


Paget's disease         5-80 years old        Sites of malignant

                                              transformation are the

                                              femur, pelvis, humerus

                                              and craniofacial bones.

Solitary enchondroma    Third decade          Diaphysis of the long

                        M = F                 bones of the hands and

                                              feet, proximal femur,

                                              and humerus.

Bone Tumor              Treatment

Periosteal chondroma    Complete excision by currettage is curative.

Osteochondroma/MHE      Surgical removal of troublesome lesions or

                        lesions which appear to possess malignant

                        potential is associated with a good outcome.

Non-ossifying fibroma   Lesions normally regress.

                        Treat only if pathologic fractures are


Paget's disease         Can vary from wide resection and chemotherapy

                        to pallitative radiation for pain control.

Solitary enchondroma    Painless enchondromas may be observed.

COPYRIGHT 2015 Universidad de Puerto Rico, Recinto de Ciencias Medicas
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2021 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Author:Martinez-Mendez, Jose Hernan; Gutierrez-Acevedo, Madeleine; Gomez-Cintron, Angel A.; Mangual-Garcia,
Publication:Puerto Rico Health Sciences Journal
Date:Dec 1, 2015
Previous Article:Anaphylactoid purpura manifested after acute gastroenteritis with severe dehydration in an 8-year-old male child: a case report.
Next Article:Rheumatic manifestations in patients with Chikungunya infection: comment on the article by Arroyo-Avila and Vila.

Terms of use | Privacy policy | Copyright © 2022 Farlex, Inc. | Feedback | For webmasters |