EURASIAN JOURNAL OF

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AVRASYA AİLE HEKİMLİĞİ DERGİSİ

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A Family with Hereditary Multiple Exostoses



Tahir Ismailoglu

Euras J Fam Med 2021;10(1):28-32. doi:10.33880/ejfm.2021100105

 

Case Report


ABSTRACT

Hereditary multiple exostoses is a rare autosomal dominant genetic disorder characterized by multiple exostoses (osteochondromas), mostly diagnosed in childhood. It may manifest with a wide spectrum from asymptomatic to skeletal deformities or neurovascular complications. Pain and/or swelling are often the first symptoms for patients to consult a doctor. Although no medical treatment is currently available, lesions can be removed with surgical excision in case of aesthetic anxiety or complications such as deformities or rarely, malign transformation. In this article, three individuals from the same family with hereditary multiple exostoses are described who were evaluated within the core competencies of family medicine.

Keywords: exostoses, multiple hereditary, osteochondroma, scoliosis


Introduction

Hereditary multiple exostoses (HME) also known as hereditary multiple osteochondromas is rarely seen as an autosomal dominant (OD) genetic disease. Exostoses are the most common benign bone tumors. It composes 10-15% of all bone tumors, with a prevalence of 1/50000 in Western countries (1,2).

In HME exostoses (osteochondromas) are characterized by cartilage lined non-malignant bone tumors. Progenitor cells of chondrocytes located in the growth plate cause osteochondroma located in the layer of the perichondrium (3). It is stated that mutations causing loss of function on the exostosin-1 (EXT1) gene located on chromosome 8 and exostosin-2 (EXT2) gene located on chromosome 11 are the cause of the disease. But it is also reported that 5-34% of patients with HME do not have any mutations in the EXT1 or EXT2 gene. This may be caused by mosaicism in the exostosin genes (4,5). The average age of diagnosis is three at childhood and more than 80% of children with HME are diagnosed at the age of 10 (2,6).

Children with HME should be monitored periodically every 6-12 months considering that problems that may be related to growth can be treated with simple interventions. Especially follow-up of the vertebral column is important due to the possibility of causing neurological damage in intraspinal exostoses (7). The swelling that occurs near the joint area is usually the first sign for patients to contact the physician. These are usually the knee, shoulder, feet, and ankle joints (5).

During childhood, the number and size of osteochondromas may increase until the growth plates are closed. Pain and functional impairment are the most common clinical problems. HME is most common in the distal femur, proximal tibia, fibula, and humerus, respectively (8). Generally, lesions in the ribs and the proximal tibia attract the first attention with their easy view and handling. They are rarely located in carpal and tarsal bones, and never seen in the facial and head bones (9). The most feared complication is the risk of malignant transformation, that is chondrosarcoma or osteosarcoma which occurs in approximately 2% of patients with HME (10). In a large multi-center study conducted in 2015, the rate of conversion to malignant transformation of HME was found 2.7% (11).

In this article, we present three men with HME without any clinical complaints and a woman with no exostoses from the same family. The lesions of exostoses are usually seen in the male sex and the same area of the body. Informed consent was obtained from all cases.   

Case 1

Our first case was a 78-year-old male patient who applied to our laboratory for routine control and periodic inspection. In his history and clinical examination, multiple swelling and irregularities on the left knee left hip, and chest wall which stated since childhood were noted. He did not want to have additional radiography for these regions except for postero-anterior (PA) chest radiography. It was learned that his father and grandfather also had such lesions. And he also stated that he had three children, two boys in whom these lesions were present, and a girl with no lesions. The boys of our patients were evaluated as cases 2 and 3. The daughter of our patient was evaluated as case 4 (healthy case).

Figure 1. Chest X-ray of Case 1. Irregularity at the right 3rd and 4th ribs and an exophytic extension with 6x2 cm in size consisting of radiolucent and dense components lateral to the ribs are seen (Also, in the mid-lower zone a calcified nodular lesion with 3.5x2 cm in size is seen).

Case 2

Our second case was a 43-year-old male patient who applied to our laboratory for routine control and periodic inspection. In the clinical examination, swelling and irregularity on the left clavicle and back, on the left tibia were detected. The lesion of the left clavicle was visible. The patient stated that he had swelling in these areas since childhood. He did not want to have additional radiography for these regions except for PA chest radiography.

Figure 2. Chest X-ray of Case 2. Exocytosis with irregular inferior contour was observed, containing 4x3 cm radiolucent components superposed with the left clavicle and 1st rib. 

Case 3

Our third case was a 47-year-old male patient who applied to our laboratory for routine control and periodic inspection. Clinical examination attracted attention to the swelling and irregularity on the right chest front area which was visible. The patient reported a soft tissue swelling in this area, present since childhood. He also said that he had a surgical operation in his youth on his left leg with the diagnosis of exostoses. Except for PA chest radiography, he did not want to have additional radiography. 

Figure 3. Chest X-ray of Case 3. Scoliosis to the left was observed in the thoracic column. A deformed appearance was observed in the right hemithorax ribs, as well as a lobulated contoured radiodense lesion compatible with exocytosis, 10x5 cm in size superposed with the front springs of the 3-6th ribs.

Case 4 (Healthy case)

In the physical examination of the 46-year-old daughter of the first case, no swelling and pathological condition in the upper and lower extremities was detected. In her story, it was confirmed that she did not have exostoses like other members of the family. Her chest radiography revealed no exostoses in contrast to other cases. PA chest radiography of our patient was evaluated within normal limits (Figure 4).

Figure 4. Normal chest X-ray of the Case 4.

Discussion

HME is an OD genetic disorder. In more than 50% of patients, HME can be passed down from an affected parent, usually the father (5). The history of our family with HME revealed that inheritance was from the father and that such lesions were also present in the father and grandfather of Case 1.

HME is usually diagnosed at the ages of 10-12 in childhood. Although all three cases were adults (Case 1 elderly), they stated in their stories that they were diagnosed in childhood-adolescence. They also said that these lesions were also present in their cousins on the father’s side. 

In HME lesions can be seen in all bones with enchondral ossification. Usually, in the long bones, it develops near the growth plate of the ribs, pelvis, and vertebrae. They are never seen in facial and head bones and rarely in carpal and tarsal bones. Exostoses on ribs and clavicle were revealed on the PA chest X-ray performed on all three members of our family. As in the description of HME, no lesions were detected in faces and heads. 

While there is no medical treatment, surgical treatment for resection, rib shortening, and deformity correction is the only treatment option in symptomatic cases or cases with a suspicion of a malignant transformation. Exostoses at ribs and proximal tibia are easy to detect and handle. Thus, they are more appealing aesthetically (12). Our cases have been living for a long time with their existing lesions and did not describe any clinical symptom. Only Case 3 stated that he had a resection of the lesion on his left leg in his twenties due to aesthetic concerns. 

Studies show that patients with HME may have a low quality of life. It has been reported that many patients may lag behind in sports activities and social life due to frequent chronic pain syndromes (13). In contrast, all of our cases stated that they do regular sports/exercises. This may be attributed to the high level of the intellectual capacity of our patients. 

With conventional radiography, diagnosis of HME can be confirmed and information about disease progression can be obtained. In patients with clinical complaints and in ones in whom complications should be evaluated, magnetic resonance (MR) is the imaging of choice (5).  In all three cases of us, no evident clinical symptoms or signs were present indicating a complication. Thus, no additional MR imaging and other advanced examination were needed. In all three cases, the diagnosis was accomplished with chest radiography.

HME related scoliosis has also been described in the literature. A recent study stated that scoliosis is one of the common components in HME and that ≥20˚ angled moderate scoliosis is decisive for the severity of HME (14).  Within our patients, mild scoliosis to the left side was noted only in one (Case 3) at the thoracal column on his chest X-ray. 

Solitary osteochondromas do not require a routine follow-up. However, patients with HME should be followed clinically and radiologically for skeletal deformities and complications, especially for the risk of developing chondrosarcoma. It should be kept in mind that HME lesions can be seen on the ribs and/or on the clavicle, on the upper humerus, and scapula. Although radiographs are sufficient to reveal the deformity, MR imaging should be performed to reveal sarcomatous transformation (15).  It is stated that individuals between 30 and 50 years of age with HME have a probability of malignant transformation with a 0.1% incidence per year (10). Therefore, we emphasized the importance and continuation of routine clinical and radiological follow-up for our Case 2 and 3. 

In conclusion, we presented here three cases of HME in the same family. HME is a rare genetic disorder that may first be seen and diagnosed by a family physician, and core competencies of family medicine practice play an important role in the management of such diseases with low prevalence. HME is a disease that needs long-term patient management. With that regard, knowledge of HME is essential as it can be diagnosed easily, mostly with the help of conventional radiographs that save time and expenses. Specific problem-solving skills of family medicine are also needed to ease the process of long-term patient management in HME such as patient referral, providing information on the genetics of the disease, and screening of other individuals in the family. It should also be kept in mind that most patients are diagnosed in childhood, and the skeletal deformities may have unwanted psychosocial consequences, as mentioned in the Case 3. Moreover, patients with HME should be followed for skeletal deformities and neurovascular complications, especially (despite rare) for a malignant transformation. All of these aspects indicate that a patient-centered, comprehensive approach is needed in HME that can be achieved by family medicine practice.

References

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How to cite: Ismailoglu T. A family with hereditary multiple exostoses. Euras J Fam Med 2021;10(1):28-32. doi:10.33880/ejfm.2021100105.


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