Temtamy, Samia A.a; El Azeem, Ahmad F. Abdb; El Badry, Tarek H.b; Mehrez, Mennat Allah I.b; El Kassaby, Marwac
aDepartments of Clinical Genetics
bOro-Dental Genetics, National Research Centre (NRC)
cDepartment of Oral and Maxillofacial Surgery, Faculty of Dentistry, Ain-Shams University, Cairo, Egypt
Correspondence to Samia Temtamy, Human Genetics & Genome Research Division, National Research Centre, El-Buhouth St. Dokki, Cairo, 12111, EgyptTel: +2 012 3410603; fax: +2 02 3370931; e-mail: firstname.lastname@example.org
Received February 25, 2011
Accepted April 3, 2011
Introduction: Cherubism a nonneoplastic bone lesion characterized by marked fullness of the cheeks and jaws and a slight upturning of the eyes revealing a rim of white sclera beneath the iris giving children a cherubic appearance.
Case report: In this report we describe the clinical features of a 14-yaer-old girl with a severe case of cherubism affecting both her jaws and we summerize the natural history of the disease over a period of 11 years.
Conclusion and recommendation: It is mandatory to perform a thorough clinical genetic evaluation to rule out cherubism associated with Noonan- like syndrome. Innovative pharmacogenomic and bioengineering approaches are desperately needed for the management of fierce recurrences of the disease after surgical intervention.
According to the WHO classification, cherubism belongs to a group of nonneoplastic bone lesions that affect the jaws (Pindborg and Kramer, 1971). Cherubism was first described in 1950 by Jones who described a condition affecting three siblings, which was characterized by marked fullness of the cheeks and jaws and a slight upturning of the eyes revealing a rim of white sclera beneath the iris giving the children a cherubic appearance (Jones et al., 1950).
Cherubism is a hereditary disease with an autosomal dominant pattern of inheritance (OMIM: 118499). Sporadic cases have been also reported. (Anderson and McClendon, 1962) reviewed 65 cases from 21 families and suggested that the pattern of inheritance is autosomal dominant. Mangion et al. (1999) mapped the gene to 4p16.3 in two dominant families. Tiziani et al. (1999) provided similar results from four families. Ueki et al. (2001) demonstrated mutations in the SH3BP2 gene. Jafarov et al. (2005) stressed that patients with cherubism should be carefully evaluated for Noonan syndrome, as they found that PTPN1 mutations in patients with cherubism in fact had Noonan syndrome. Clinically, in cherubism, the lesions usually start in early childhood, affect both jaws, and have a symmetric distribution. It begins to swell gradually until puberty. Although the condition is known to regress spontaneously during the third decade of life, surgical management is sometimes required for cosmetic reasons (Anderson and McClendon, 1962; Peters, 1979).
Although the disease is rare and painless, the afflicted suffer the emotional trauma of disfigurement. The effects of cherubism may also interfere with normal jaw motion and speech. Currently, surgical removal of the fibrous tissue and bone is the treatment available. This treatment has no expected results, and most of the time, when introduced before puberty, results in an increase in bone growth (Tiziani et al., 1999).
The use of calcitonin and bisphosphonate with these surgeries was found to enhance the outcome greatly and to prevent fierce recurrences, taking into consideration the fact that growth stops by the third decade, although the radiological changes persist until the fourth (De Lange et al., 2007).
This report describes the clinical features of a 14-year-old girl with a severe case of cherubism affecting both jaws. We summarize the natural history of the disease over a period of 11 years.
The patient presented to the Maxillofacial Department, Nasser Institute of Health (NIH), for the first time at 2 years of age complaining of mild bilateral swelling in the maxilla and mandible. By clinical and radiographic examination, the case was diagnosed as cherubism (Figs 1 and 2).
After follow-up for 4 years by successive teams of the NIH Maxillofacial Department, the complication of continuous and gross enlargement of maxilla and narrowing of fissures and spaces of the maxillofacial component occurred, placing pressure on the optic nerve, resulting in bilateral partial optic atrophy and vision impairment (Fig. 3).
The pathology report of a biopsy taken from the orbital floor at this stage revealed multiple areas of fleshy grayish tissue with small bony spicules in gross picture. By microscopic examination of a serial of sections, tumor tissue showed multinucleated giant cells surrounded by stromal cells with focal spindling, thin-walled vessels, and hemorrhagic foci with few necrotic bony spicules.
An emergency surgical procedure to relief the pressure on the optic nerve was attempted. Following surgery, the patient showed marked changes and severe aggravation of the condition (Fig. 4a and b).
The current maxillofacial surgery team at the NIH considered genetic counseling with the Oro-Dental and Clinical Genetic Departments at the NRC. The patient who is now 14 years old was investigated and the following was revealed:
Transthoracic echo/Doppler showed thickened mitral valve leaflets and prolapsed anterior leaflet, mild mitral regurgitation, and intra-atrial septum: Patent foramen ovale.
Abdominal ultrasonography showed normal results for the liver, gall bladder, spleen, pancreas, kidneys, urinary bladder, and pelvis. A much distended colon was seen.
Three-dimensional multislice computed tomography of the maxillofacial bone regions shown in Fig. 5a revealed that the whole mandibular and maxillary bones were markedly expanded bilaterally by a large multicystic bony lesion showing big lakes and densely calcified septa with marked expansion and pressure erosion of their cortical outline. The expanded bones were totally obliterating the nasal cavity and all paranasal sinuses, encroaching on the nasopharyngeal airway, with marked encroachment on the inferior aspects of both orbits, causing bilateral proptosis. Both of the greater wings of the sphenoid bones were displaced totally with no involvement of the lateral sphenoid, zygoma, and zygomatic arch. No intracranial or epidural extension was noted, with normal posterior fossa and cerebral hemispheres.
MRI of the orbits with contrast revealed an expansile osseous lesion in which the involved bones were replaced by an abnormal soft tissue proliferation that showed heterogeneous postcontrast enhancement. This presentation is related to fibrous dysplasia. The maxillary bone lesion had nearly obliterated the maxillary sinuses and markedly compressed the bony orbits bilaterally. The orbits consequently showed abnormal remodeling with attenuation of the orbital space. Bilateral proptosis consequently developed with associated crowding of the orbit contents (Fig. 5b).
Orodental and maxillofacial examination showed the following: open mouth and incompetent lips with exposure of the alveolar ridges; gingiva was fibrous and firmly stretched over massive alveolar ridges with displaced teeth (Fig. 6). The massive expansion of the mandible resulted in posterior displacement of the tongue and severe narrowing of the velopharyngeal space. The expansion of the maxilla was causing severe nasal disfigurement and obstruction. Facial skin was extremely stretched. There was also severe displacement of the orbital contents because of the pressure from the overgrowth causing exophthalmia and increased exposure of the sclera, leading to the cherub look, conjunctivitis, severe vision impairment, and inability to close the eyes (Fig. 7).
Although cherubism is not usually fatal, it severely affects the quality of life. Fatalities are usually due to airway obstructions and surgical intervention is the only life-saving option, which is shadowed by fierce recurrences. New approaches combining calcitonin and bisphosphonates with surgical treatment appear to be promising.
Conclusion and recommendation
The patient with cherubism should have thorough clinical genetic evaluation to rule out the diagnosis of cherubism associated with the Noonan-like syndrome. There is a lack of standardized treatment protocols for patients with cherubism. As pointed out by Tiziani et al. (1999), cooperation between surgeons and geneticists is mandatory. Innovative research is needed to hinder the bony overgrowth. This could be achieved by using modern robust genetic methodologies to find out the etiopathogenesis of the disease. Pharmacogenomic and bioengineering approaches are also needed for the management of cherubism.
Conflicts of interest
There are no conflicts of interest.
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