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J Curr Ophthalmol
J Curr Ophthalmol
JCO
J Curr Ophthalmol
Journal of Current Ophthalmology
2452-2325
Wolters Kluwer - Medknow India

JCO-35-411
10.4103/joco.joco_128_23
Case Report
Hereditary Multiple Exostoses with Rare Ocular Finding: A Case Report
Tanwar Shashi 1
Saini Nishtha 1
Boriwal Krutika 1
Sharma Prashant 2
1 Department of Ophthalmology, Shaheed Hasan Khan Mewati Government Medical College, Nuh, Haryana, India
2 Department of Orthopaedics, Satyawadi Raja Harishchandra Hospital, Narela, Delhi, India
Address for correspondence: Shashi Tanwar, Department of Ophthalmology, Shaheed Hasan Khan Mewati Government Medical College, Nalhar, Nuh, Haryana, India. E-mail: shashitanwar75.st@gmail.com
Oct-Dec 2023
10 8 2024
35 4 411414
03 7 2023
12 10 2023
13 10 2023
Copyright: © 2024 Journal of Current Ophthalmology
2024
https://creativecommons.org/licenses/by-nc-sa/4.0/ This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
Purpose:

To study rare ocular findings in a rare case of hereditary multiple exostoses (HME) and to study HME in one family.

Methods:

HME is an autosomal dominant genetic disease characterized by the presence of multiple exostoses (osteochondromas). It is caused by mutations in two genes: exostosin-1 (EXT1) and exostosin-2 (EXT2). We report HME in a family over three generations. The index case was a 14-year-old female who presented with an ocular mass and multiple hard nodules in the upper and lower limbs. Family history revealed similar multiple nodules in the younger brother, father, and grandfather. Hence, the paternal family history for HME is positive. All the family members were examined. Family members who were diagnosed with HME had a series of radiology tests completed. Furthermore, the family members with HME were also seen by an orthopedic surgeon.

Results:

Family history and physical examination revealed multiple exostoses in the younger brother, father, and grandfather. They were all diagnosed with HME. The index case also had an ocular surface mass with scleral ectasia in the right eye.

Conclusion:

HME is a rare, genetic disorder. Cases of HME with ocular findings are rare. This patient has a paternal family history of HME and presents with an ocular surface mass.

Exostoses
Exostosin
Hereditary multiple exostoses
Hereditary multiple osteochondromas
Ocular surface mass
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pmcINTRODUCTION

Hereditary multiple exostoses (HME) is a rare genetic disorder with autosomal dominant transmission. HME is also known as familial osteochondromatosis, diaphyseal aclasis or hereditary multiple osteochondromas (HMO).1 HME is characterized by an abnormal proliferation of bone protuberance that results in exostoses formation, particularly involving the metaphysis of long bones.2 Studies have shown that HME is caused by mutation in the exostosin-1 (EXT1) and exostosin-2 (EXT2) genes.2 Exostoses form at the growth plates of bones. These areas include ribs, pelvis, vertebrae, and particularly the long bones.3 HME with ocular findings is rare.

CASE REPORT

Informed consent was obtained from all of the patients involved. A 14-year-old female presented with a painless progressive swelling in the right eye noticed by her parents when the child was 3 years old. Her visual acuity was 20/20 in both eyes, and intraocular pressure was 14 mmHg in both eyes on applanation tonometry. On slit-lamp examination, the right eye had an elevated reddish nodular lesion. It had well-defined margins and measured approximately 5 mm × 5 mm with an irregular surface and sentinel vessels present at the temporal aspect of bulbar conjunctiva at 9 o’clock encroaching up to ~1 mm of the temporal part of the cornea with haziness of surrounding cornea. As shown in Figure 1a, the lesion was nontender, firm, and adherent to the underlying sclera. There was inflammation associated with the lesion, and the surrounding bulbar conjunctiva had increased pigmentation. In the superior portion of the cornea, there was superficial vascularization. As shown in Figure 1b, there was scleral ectasia in the superior portion at 11 o’clock, 2–3 mm away from the limbus. The ectasia measured ~2 mm × 3 mm with herniation of underlying uveal tissue. The rest of the anterior segment, the left eye, and the fundus in both eyes were normal. There was no history of any ocular trauma. Anterior segment optical coherence tomography (Topcon 3d OCT-1 [Ver. 8.42], Topcon Corporation, Japan) revealed a spherical-shaped hyperreflective lesion with hyperreflectivity of the underlying cornea and sclera [Figure 1c]. The patient also presented with a history of recurring painless swelling in the forearm, leg, and knee joint since 3 years of age. As shown in Figure 2a and b, general physical examination revealed multiple, nontender bony prominences with swelling over the forearm, leg, and knee joints. Both the systemic and hematological examinations were within normal limits. Figure 2c displays the radiological imaging which reveals multiple exostoses around the knee joint and forearm. The family history revealed similar episodes of swelling in the younger brother, father, and paternal grandfather. Radiological investigation of them showed multiple exostoses [Figure 3]. The index case and all affected family members were examined by an orthopedic surgeon. Following the diagnostic imaging and appropriate examinations, a diagnosis of HME was confirmed. None of the affected family members had a history of ocular issues. In consideration of the ocular mass present on the right eye, and HME, a final diagnosis of HME with ocular surface mass with scleral ectasia was confirmed in the index case.

Figure 1 Slit-lamp image of the right eye showing ocular surface mass (a), scleral ectasia with herniation of uveal tissue (b), and anterior segment optical coherence tomography of the right eye showing spherical-shaped hyperreflective lesion with hyperreflectivity of the underlying cornea and sclera (c)

Figure 2 Multiple exostosis diseases: Clinical (a and b) and radiological images (c) of exostosis in the metaphyses of the bones of the upper limb and lower limb

Figure 3 Multiple exostosis diseases: Radiological images of younger brother showing exostosis in the metaphyses of the bones of the upper and lower limbs

DISCUSSION

HME is a rare, autosomal dominant disorder of benign bone tumors that are surrounded by a cartilage layer and arise from the metaphysics of long bones.23 In 1814, Boyer reported the first case of HME, which was present in a French family.4 The reported prevalence of HME is 1:50,000 in the Western populations. However, cases of HME are rare in the Indian population.56 HME is genetically heterogeneous with incomplete penetrance in females. The male-to-female ratio is 1.5:1.67 Sixty percent of patients with HME have reported a family history of HME.3 The literature review shows that 80%–90% of cases of HME are associated with a mutation in tumor genes EXT1 and EXT2.236789101112 While an EXT3 gene located on the short arm of chromosome 19 has been hypothesized to play a role, its role in HME has yet to be determined.13 EXT1 and EXT2 are located on chromosome 8q24.11-q24.13 and 11p12-p. 11, respectively.26 EXT1 and EXT2 gene code for transmembrane type II glycoproteins, exostosin 1 and 2. These proteins contain glycosyltransferase which is responsible for the polymerization of heparan sulfate (HS). HS is required for proper cartilage development and long bone growth. A mutation in these genes results in an HS deficiency which causes abnormal proliferation and differentiation of chondrocytes without ossification of the perichondrium. This explains the growth of ectopic cartilage.23

HME usually presents during the childhood (3 years) and teenage years (10–12 years). Exostoses involve bones that develop from cartilage. The common sites are the distal femur, proximal tibia, fibula, and humerus. Vertebra, ribs, and flat bones like the iliac and scapula are less frequently involved. However, bones such as the skull, mandible, and facial bones that are formed by intramembranous ossification are not involved.26

Exostoses are usually painless, benign lesions that remain asymptomatic. However, patients may present with skeletal deformities such as short stature, limb-length discrepancies, valgus deformities of the knee and ankle, asymmetry of the pectoral and pelvic girdles, and bowing of the radius with ulnar deviation of the wrist. Other complications include compression effects, vascular and neural complications, and malignant transformation. Malignant transformation is seen in 0.5%–5% of HME cases.236

HME with ocular involvement is rare. After reviewing the current literature (PubMed, open access journals, Medknow publications, and Google Scholar), HME with ocular involvement has not been reported before. This patient presented with a mass in her right eye at our hospital. She has a paternal family history of HME. None of her family members with HME have ocular issues. The family members with HME present primarily with swelling in their limbs (exostoses). Unfortunately, this patient was lost to follow-up, and we could not complete the necessary molecular and pathological analyses. This case provides a new perspective as there was an ocular complication associated with HME. Moving forward is helpful to keep this in mind when considering HME.

In conclusion, very few cases of HME are reported. After a thorough review of the literature, we are not aware of any other case of HME with ocular involvement being reported before. Therefore, we have reported this case with the intention that it will contribute to the medical literature.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understand that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.
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