Cherubism: Rare fibro-osseous dysplasia

Case based discussions with panel Q&As
Cherubism: rare fibro-osseous dysplasia
Presenter: Grusha Y.

Cherubism is a rare, genetic, fibro-osseous dysplasia which presents with progressive bilateral upper and lower jaw enlargement, with typical facial characteristics. First described by Jones W.A. in 1933, there are about 300 reported cases in the literature, the facial features bearing a passing resemblance to a biblical cherubims. It is inherited in an autosomal dominant manner, with a higher penetration among males, manifesting in the first decade, and progressing over 4 decades. Elevated serum TNF-alpha levels are implicated in the aetiology, with remodelling of normal bone to fibrous tissue and cyst formation; mineral metabolism, however, is normal. Spongiform bone formation leads to early tooth loss, mandibular and maxillary enlargement, with involvement of the zygomatic arch in some cases. Orbital involvement is very rare, tending to occur in advanced cases. Clinically, in the most severe cases, this can lead to  globe dislocation, ophthalmoplegia, optic nerve compression and macular striae and scarring.

Our patient is a 31 year old Russian lady with positive family history of the disease. She was diagnosed with cherubism at the age of eight years, and had been exophthalmic from the age of 14 years. Unfortunately I don’t have permission to show you photos of her face, only computed tomography scans will be presented. Four years ago, in 2015, she reported pain and diplopia in supra-dextra elevation of the right eye, progressing over the course of a year. Ophthalmic examination identified good visual acuity and colour vision, without evidence for optic neuropathy, but with 6 mm relative exophthalmos on right side. She had restricted ocular ductions to the right with some diplopia and discomfort, and inferior displacement of the lower eyelids. CT imaging identified bilateral involvement, being more significant on the right, and with the patient reporting pain on that side .

The advice in general is that, in the absence of medical treatment, surgery should be considered. However, the patient is good-looking and her visual functions were otherwise intact. Nevertheless, she had lagophthalmos, and there remained the question of whether she would develop optic nerve compromise in future. For this reason, we proceeded with orbital surgery on the right.

A swinging eyelid approach was used. Here you see the lesion on the orbital floor, with partially displaced maxilla, and the globe is here. A lot of drilling was required to achieve a debulk, with haemorrhage from cavities extending into the cortical bone, which had a very dense structure, with the entire procedure taking over three hours. I’ve left some bone here, close to the optic nerve, because it was very difficult to differentiate between the lesion and the remaining orbital structures.

Histology identified high osteoclastic activity, with an osteoclast shown here with vessels and lymphocytes. DNA diagnostics identified a p.P418L mutation in the SH3BP2 gene, this being relevant because she was planning to have a child. That was four years ago, and two and a half years ago the patient gave birth to a healthy daughter.

Within a short period of time she presented with sudden worsening of her visual acuity and colour vision on the right, a relative afferent pupillary defect, and optic nerve swelling, although she had had a reasonable repositioning of the globe following the first operation. This is the optic nerve and the OCT changes on the right side. She proceeded to a second operation, undertaking further debulking using a high-speed burr, guided by an intraoperative navigation system. It was major with near total dissection of the right orbit lesion.

One month post-operatively her visual acuity had improved to the level prior to the first operation, with a good globe position with a 1 mm relative exophthalmos, no relative afferent pupillary defect, normal colour vision, and significant improvement of diplopia. This slide shows the OCT scan before surgery in December 2017, and this is one a year after surgery, the OCT identifying improvement, although with minor deterioration of the left eye, for which she did not want surgery.

These CT scans show the results of the surgery, pre- and post-operatively. It was possible to remove all the inferior lesion, and there was no non-axial globe displacement, or displacement of the inferior rectus, an no implant was required.

In the conclusion, patients with disease such as cherubism require a multidisciplinary approach, including surgeons, geneticists and experts in reproductive medicine. Severe orbital involvement is rare, and surgery is difficult, requiring major mass debulking to be effective for patients with significant optic neuropathy.

Cherubims are special winged upon whose wings God’s throne rests. They stand around the throne serving as an elite bodyguard unit – God’s ‘heavies’. (Ezekiel, Old Testament). So perhaps because of that, here we are in The Cavalry and Guards Club, with some Russian culture, with Cherubs having a characteristic appearance in Russian Christian tradition.