Orbital osteomas associated with Gardner’s syndrome: a case presentation and review of literature

ABSTRACT Gardner syndrome (GS) is a rare genetic disorder characterized by numerous intestinal colon polyps with various extraintestinal manifestations. Osteomas are a known extracolonic manifestation of GS and can affect the orbit, as seen in our patient, as well as 13 other cases documented in literature. Excision of large orbital osteomas can be successful with a multi-disciplinary approach as presented in this article. Ophthalmologists can even be the first to diagnose GS, usually via the presence of congenital hypertrophy of the retinal pigment epithelium (CHRPE) lesions. Untreated, 100% of colon polyps will transform into cancer, thus it is important to be aware of this rare syndrome with ophthalmic manifestations and screen patients with osteomas for GS.

Gardner syndrome (GS) is a rare genetic disorder with autosomal dominant inheritance characterized by numerous intestinal adenomatous polyps with various distinct extraintestinal manifestations. 1 It was first described in 1951 by the geneticist Eldon Gardner 2 with mutations specific to the Adenomatous Polyposis Coli (APC) gene later identified in 1991. 3,44][5][6][7] Although the preferred terminology for Gardner's Syndrome is now FAP, the eponym is still widely used thus the authors will use this reference synonymously.
The incidence of GS is approximately 1 in 7000 to 1 in 30,000 births, affecting men and women equally with variable expressivity. 1,6,7Although a strong family history is typically present, 20-30% of cases arise from de novo mutations. 1,6,7[10][11][12] Osteomas are benign tumors of osteogenic origin.][10][11][12] Their prevalence is even more common in Gardner's syndrome and can be found in 60-80% of patients with FAP, affecting any part of the skeleton but more commonly the frontal bone, maxilla, and mandible. 8,9rbital osteomas are exceedingly rare, representing less than 10% of tumors affecting the orbit. 13When present, it is typically an extension from the adjacent paranasal sinuses, typically found incidentally on imaging performed to evaluate other pathology.Rarely, these tumors grow slowly, causing globe displacement, diplopia, and compressive optic neuropathy, warranting surgical excision. 13We report a case of an orbital osteoma associated with GS and present findings from a comprehensive review of similar reports with a focus on clinical features, management, and surgical resection.This study adhered to the principles outlined in the Declaration of Helsinki and was HIPAA compliant.The patient consented to publication of identifiable photographs.

Case presentation
The patient is a 49-year-old female with known Gardner's syndrome who presented with worsening right-sided proptosis and diplopia over several months (Figure 1).Exam was notable for 20/40 vision in the right eye and 20/20 vision in the left eye.Intraocular pressures were 15 mmHg bilaterally, and pupils were reactive without an afferent pupillary defect.The right eye was noted to have an abduction deficit, hypoglobus, and 6 mm of proptosis by Hertel ophthalmometry.External exam showed numerous firm facial lesions and surgical changes over the mandible, consistent with a prior history of mandibulectomy for desmoid tumors.Dilated fundus exam showed various lesions consistent with congenital hypertrophy of the retinal pigment epithelium (CHRPE) in the right eye.The left eye was normal.
A computed tomography (CT) scan was obtained, showing a large osseous lesion arising from the ethmoid sinus and entering the right medial orbit (Figure 2).Given her diagnosis of GS, an orbital osteoma was presumed the most likely diagnosis.The surgical approach  consisted of a combined lateral and medial orbitotomy performed in conjunction with a functional endoscopic sinus surgery (FESS) approach by a rhinologist.A lateral orbitotomy was performed through an extended lid crease incision where the lateral orbital rim was taken down to facilitate mobilization of the globe laterally, allowing better exposure of the medial orbital wall and tumor.
Traction sutures were placed along the superior and inferior rectus and the globe was distracted laterally.A transcaruncular incision was then made with extension into the superomedial and inferomedial fornices and the orbital portion of the tumor was exposed (Figure 3a).The intranasal component was first debulked using a cutting drill under endoscopic visualization after an ethmoidectomy was performed (Figure 3b).After significant intranasal debulking, the orbital component was similarly debulked.The remainder of the tumor was freed from the surrounding soft tissue and delivered through the orbital incision (Figure 3c).Pathological examination confirmed a mature osteoma.Six months postoperatively, the patient noted improvement in diplopia and proptosis (Figure 4).

Discussion
Gardner's syndrome can be a devastating condition.Patients will develop intestinal polyps in childhood and by age 35 years, 95% of patients will have colorectal adenomas.If left untreated, 100% of patients will develop colorectal carcinoma in their lifetime.Ophthalmologists are an important part of the care team and can even be the first to diagnose GS, usually via the presence of retinal congenital hypertrophy of the retinal pigment epithelium (CHRPE). 14,15While retinal CHRPE lesions are seen in 1.2-4.4% of the general population, it has a prevalence of 90% in patients with GS and the associated APC mutations. 14,15It is usually present at birth and is the  most common and earliest extraintestinal manifestation of FAP populations. 14,15The presence of a CHRPE lesion on fundoscopy is a harbinger for FAP, and the ophthalmologist should reflexively screen for FAP when it is discovered as extracolonic manifestations can precede the diagnosis of GS.Suspected patients should have a complete work-up for GS, including lower gastrointestinal tract endoscopy, barium enema imaging, colonoscopy, and genetic testing.Our patient had a known history of CHRPE lesions for which she followed with a retina specialist.
Osteomas are an important extracolonic component of GS and have been reported to be present in 60-80% of patients with GS.7][18][19][20][21][22][23][24][25][26] There was a male predominance (77%), and average age was 32 years.Like most orbital osteomas in non-syndromic patients, all orbital osteomas involved the medial orbital wall, most from direct sinus extension.The frontal sinus was the most involved followed by the ethmoid sinus.Proptosis was the most common presenting sign (85%).Only five patients underwent surgical excision for functional reasons, including airway obstruction and diplopia.All patients had colonic polyps as well as other extraintestinal features of GS with dental abnormalities, skeletal osteomas, and soft tissue tumors being the most reported.Supplementary Table 1 summarizes our findings.
We also found many similarities between idiopathic osteomas and osteomas associated with GS.In both, the osteomas were described as circumscribed lesions and well demarcated from healthy surrounding tissues.On radiographic imaging, they were described as showing a homogenous dense bony texture, as seen in our case. 27imilar to osteomas associated with GS, idiopathic osteomas can affect the pediatric and adult populations, with patients usually being diagnosed between their third to sixth decades of life. 26,28They also similarly show a small to moderate male predominance. 29,30The authors believe no real difference exists between idiopathic osteomas and those associated with GS.However, it is very rare for normal individuals to harbor multiple osteomas, which is almost always expected in those with GS.The presence of more than one osteoma in an individual should raise suspicion for GS.Some reports further categorize osteomas according to pathological types, including ivory, compact, spongiosa, and mixed, but this is beyond the scope of this article. 31n one of the largest adult cohorts of orbital osteomas, Erdogan et al. found four cases of GS out of 64 patients with paranasal sinus osteomas. 32In a large retrospective study of 59 pediatric patients with orbital osteomas, none were found to have Gardner's Syndrome. 33This shows that although GS is rare, it is not uncommon, and physicians should be suspicious of GS when encountering patients with osteomas, particularly in adult patients.Although studies show that osteomas are prevalent in patients with FAP, there are no current studies that provide prevalence of primary orbital or orbitinvolving osteomas in this subset of patients. 8,9ooley et al. recently published a case of an orbital osteoma in a young healthy patient who underwent successful excision via a similar surgical approach, consisting of a combined lateral and medial orbitotomy performed in conjunction with a functional endoscopic sinus surgery (FESS) approach that was performed by an otolaryngologist.In their patient, the osteoma was delivered through the oral cavity instead of an orbital incision.Although a rare entity, it is important to be aware of possible surgical approaches for orbital osteomas.Given that they are often found medially involving the sinuses, a medial orbitotomy is an ideal approach.Additionally, these tumors can grow to be quite large before becoming symptomatic, thus a lateral orbitotomy is often necessary to facilitate mobilization of the globe laterally allowing better exposure of the medial orbital wall and tumor.The tumor can then be debulked under endoscopic visualization and delivered either through the orbit or the nasopharyngeal cavity.The reported follow-up was inconsistent in our literature review, but the interpretation of limited case reports suggests that these tumors grow slowly and do not typically recur when excised completely.Our patient continues to do well 1 year after surgery without evidence of recurrence.
The presence of colorectal adenomatous polyposis is the main feature of Gardner's Syndrome; however, osteomas are an important extracolonic manifestation.Given the high morbidity and mortality associated with GS, the authors recommend that patients who are found to have an osteoma be reflexively screened for FAP and questioned about gastrointestinal symptoms, history of colon polyps, family history of FAP, and other extracolonic manifestations of FAP.A dilated fundus exam can be done to look for CHRPE lesions that could help corroborate the diagnosis.Radiographic scans can show the presence of other osteomas, particularly along the axial skeleton like the skull and facial bones, which are commonly seen in GS.If suspicion is high, further work-up with colonoscopy, endoscopy, and genetic testing can confirm the diagnosis.Identifying a specific entity on the FAP spectrum through gene testing can help stratify prognosis and treatment plan.Excision of large orbital osteomas can be successful with a multi-disciplinary approach as seen in our patient.Untreated, 100% of colon polyps will transform into cancer; thus, it is important to be aware of this rare syndrome with ophthalmic manifestations and screen appropriately.

Figure 1 .
Figure 1.External photo of patient at presentation showing notable right-sided proptosis, hypoglobus and surgical changes from a prior mandibulectomy.

Figure 2 .
Figure 2. Axial CT scan showing a large osseous tumor in the right medial orbit as well as other smaller osteomas along the skull.

Figure 3 .
Figure 3. (a): Intraoperative photograph demonstrating lateral displacement of globe into a surgical lateral bony window increasing medial transorbital access into sinuses.(b): Intraoperative photograph demonstrating drilling and debulking of osteoma under endoscopic visualization.(c): Intraoperative photograph showing debulked and excised osteoma.

Figure 4 .
Figure 4. External photo of patient 6 months postoperatively showing improvement in right-sided proptosis and hypoglobus.