Surgical Treatment of Cherubism With the Use of ThreeDimensional Virtual Planning and CAD-CAM Resection Guides: A Case Report and Systematic Literature Review.

ABSTRACT: We report the use of a three-dimensional virtual surgical planning technique including both fusion and superimposition to obtain harmony and symmetry of the face in an 18-year-old woman suffering from cherubism. The treatment contained several threedimensional techniques that allowed precise planning and a predictable surgical outcome. The reduction plasty was successful, and the postoperative healing was uneventful. No relapse of the disease occurred after the surgical treatment and the sensation of the mentalis area recovered. The patient was satisfied with the aesthetic result and no additional surgery was needed. The surgical planning techniques described, and the CAD/CAM patient-specific resection guides seems to be safe and reliable in a one-step surgical treatment of cherubism patients after the disease has clearly ceased based on radiological findings. A systematic review of the literature on surgical correction of deformities due to cherubism was conducted. The systematic review of the existing literature was performed on the available studies from PubMed and Ovid Medline published before June 9, 2020. The search term was ''Cherubism.'' The inclusion criteria were: 1) full article published in English and 2) the patient had surgical treatment. We excluded the cases that included only minor surgery as biopsy or only treatment of unerupted teeth. The database identified 638 citations of which 50 met the eligibility criteria. The systematic review revealed no earlier use of surgical 3D planning in the treatment of cherubism.

Crecimiento mandibular bilateral: un caso de querubismo / Bilateral swelling of the jaws: a case of querubism

El querubismo es una displasia ósea benigna de la infancia caracterizada por un crecimiento mandibular bilateral progresivo. Presenta herencia autosómica dominante y es más frecuente en varones. Las primeras manifestaciones aparecen en torno a los dos años de edad, con un crecimiento óseo acelerado a los 8-9 años e interrupción espontánea tras la pubertad. El diagnóstico se basa en la clínica, radiología y anatomía patológica. El tratamiento es controvertido, incluyendo tratamiento médico o quirúrgico. Presentamos el caso de un varón de nueve años que consultó por crecimiento mandibular bilateral, requiriendo finalmente extirpación quirúrgica de las lesiones (AU)

Cherubism is a benign bone dysplasia characterized by bilateral progressive enlargement of the jaws. It is an autosomal dominant disease and boys are more affected than girls. The first signs of manifestation of the disease are generally observed at about two years of age, followed by accelerated growth from 8-9 years of age and spontaneous interruption after puberty. The diagnosis is based on clinical, radiographic and histopathologic findings. Treatment is a controversial issue and therapy strategies include surgical treatment and medical treatment. We describe the case of a nine-year-old boy with bilateral swelling of the jaws who required surgical treatment. (AU)

Cherubism and anaesthesia.

Respiratory complications are one of the main problems in paediatric anaesthesia. Cherubism is a rare fami-lial disease causing enlargement of the mandible that may be associated with difficult intubation [1, 2]. A 5-year-old, 20 kg, ASA 1, healthy girl was evaluated for anaesthesia requested for the removal of mandibular lesions (Figure 1). She had a positive family history of cherubism; her father and cousins were affected. Radiogra-phically, the lesions demonstrated multilocular, expansile radiolucencies with mandibular enlargement. The preoperative examination was unremarkable: normal neck flexion, no trismus, and a Mallampati score of 1. A venous catheter was inserted peripherally under N2O inhalation and transdermic lidocaine and prilocaine patch. The general anaesthesia combined sevoflurane and IV sufentanil. Nasotracheal intubation under direct laryngoscopy was uneventful. After the surgery, which lasted 120 minutes, she was admitted to the post anaesthesia care unit for 1 night and discharged the next day without any sequelae.

Adjuvant Alendronic Acid in the Management of Severe Cherubism: A Case Report and Literature Review.

Cherubism is a rare disease of the jaws characterized by bilateral symmetrical painless expansion of the mandible and maxilla. In extreme cases, larger lesions can become exophytic and have profound functional and esthetic implications. Several pharmacologic agents have been trialed in the treatment of cherubism with variable success reported. Bisphosphonates have not been significantly studied in this setting. We present a case where oral alendronic acid was used as an adjuvant treatment after surgical debulking of the maxilla in a 13-year-old boy with a severe case of cherubism.

Cherubism: a systematic literature review of clinical and molecular aspects.

The purpose of this review was to integrate the clinical, radiological, microscopic, and molecular data of published cherubism cases, in addition to therapeutic approaches, to provide more concise information about the disease. An electronic search was undertaken in September 2019. Eligibility criteria included publications having enough clinical, radiological, and histological information to confirm the diagnosis. A total of 260 publications reporting 513 cherubism cases were included. Familial history was observed in 310/458 cases (67.7%). SH3BP2 mutations were reported in 101/108 cases (93.5%) and mainly occurred at protein residues 415, 418, 419, and 420. Retrospective clinical grading was possible in 175 cases. Advanced clinical grading was associated with tooth agenesis, but not with other clinical, radiological, and genetic features. Specific amino acid substitutions of SH3BP2 mutations were not associated with the clinical grading of the disease. 'Wait and see' was the most common therapeutic approach. In a small number of cases, drugs were used in the treatment, with variable response. In conclusion, there is no clear correlation between the genotype and the phenotype of the disease, but additional genomic and gene expression regulation information is necessary for a better understanding of cherubism.

Cherubism as a systemic skeletal disease: evidence from an aggressive case.

BACKGROUND: Cherubism is a rare autosomal dominant genetic condition caused by mutations in the SH3BP2 gene. This disease is characterized by osteolysis of the jaws, with the bone replaced by soft tissue rich in fibroblasts and multinuclear giant cells. SH3BP2 is a ubiquitous adaptor protein yet the consequences of SH3BP2 mutation have so far been described as impacting only face. Cherubism mouse models have been generated and unlike human patients, the knock-in mice exhibit systemic bone loss together with a systemic inflammation. CASE PRESENTATION: In light of these observations, we decided to search for a systemic cherubism phenotype in a 6-year-old girl with an aggressive cherubism. We report here the first case of cherubism with systemic manifestations. Bone densitometry showed low overall bone density (total body Z-score = - 4.6 SD). Several markers of bone remodelling (CTx, BALP, P1NP) as well as inflammation (TNFα and IL-1) were elevated. A causative second-site mutation in other genes known to influence bone density was ruled out by sequencing a panel of such genes. CONCLUSIONS: If this systemic skeletal cherubism phenotype should be confirmed, it would simplify the treatment of severe cherubism patients and allay reservations about applying a systemic treatment such as those recently published (tacrolimus or imatinib) to a disease heretofore believed to be localised to the jaws.

[Unique Experience of Cherubism Targeted Therapy].

The family form of giant cell reparative granuloma or cherubism is a rare benign lesion of the jaws which causes face deformation reminiscent of the cherubs portrayed in Renaissance art. Radical surgery, especially in children before puberty, is impossible or irrational, because it leads to disablement. For four years, a child with cherubism was undergoing an outpatient supervision in the Department of Maxillofacial Surgery in Russian Children Clinical Hospital. During the observation period it was noted that tumor masses were slowly progressing leading to exoorbitism. The child had a diagnosis histological verification; a treatment using human monoclonal antibodies to RANKL was developed, adapted and approved by the ethical committee. The clinical effect was observed from the third month of therapy - jaws corners sharpened, the volume reduced. The control biopsy material taken at the end of the 6-month course did not reveal any giant cells which meant complete pathomorphism. Computed tomography showed that at the end of the therapy bone density increased by 6-7 times in the affected zones and was additionally growing over the next 6 months of observation. Such dynamics allowed making effective contouring surgery of excessive bone tissues. Inoperable and early stages of cherubism require a combined treatment which includes a course of monoclonal antibodies followed by alendronic acid therapy that increases osteoblasts survival. After the treatment, if it is necessary to improve the appearance, contouring surgery of excessive bone tissue is performed.

Clinicoradiologic follow up of cherubism with aggressive characteristics: a series of 3 cases.

Cherubism is a rare autosomal dominant disorder characterized by replacement of bone with fibrous tissue containing multinucleated giant cells. It manifests as bilateral mandibular and/or maxillary enlargement. The 2017 World Health Organization classification lists cherubism as a giant cell lesion of the jaws, distinct from fibro-osseous disorders. We discuss 3 cases of familial cherubism having aggressive characteristics and present clinicoradiologic evaluations of the lesions over 12, 18, and 1.5 years, respectively. Follow-up was observational, without active intervention. Analysis of the lesions for change in size and functional impairments was correlated with periodic imaging. All patients are currently being monitored. The outcome in 2 cases has been excellent without intervention, but 1 case had extensive involvement of the jaws and involvement of the condyle and orbit. A secondary giant cell lesion involved the palate in one patient's mother, who had had cherubic lesions in childhood.

Innovative Surgical Treatment of Severe Cherubism.

BACKGROUND: Cherubism is an autosomal dominant syndrome characterized by excessive bilateral maxillomandibular bony degeneration and fibrous tissue hyperplasia. Conservative management is the preferred treatment as cherubism has a self-limiting course. Functional or emotional disturbances may, however, demand surgical intervention. We report a patient who underwent surgical intervention. METHOD/DESCRIPTION: He had significant enlargement of lower cheeks and bilateral lower lid scleral show. On computed tomography of the face, the patient had significant fibrous tissue involving bilateral maxilla and mandible. The mandibular tumor was excised. Given normal inferior border, bilateral sagittal split osteotomy was performed to infracture and inset the outer cortex. During the procedure, patient required blood transfusion intraoperatively, so the maxillary portion of the procedure was delayed until 6 months later. For the maxilla, bilateral transconjunctival approach was used to resect parts of the orbital floors that were concave, resulting in 1 × 2 cm defects bilaterally which were reconstructed using resorbable plates. Then the anterior maxillary tumor was excised. RESULTS: The patient and his parents were satisfied with his appearance after surgery. The patient was noted to have improvement in contour and decreased scleral show. He has most recently followed up 15 months after the initial surgery. There were no long-term complications. CONCLUSIONS: Severity of cherubism influences the type of surgical intervention. The present case is innovative because this is the first reported case of recontouring orbital floors with resorbable plates and infracturing of the mandible using sagittal split osteotomies for surgical treatment of cherubism.

Orthodontic management of a patient with cherubism: A case report.

INTRODUCTION: The aim of this case report was to present the successful orthodontic treatment of an adolescent girl with cherubism. METHODS: The patient began treatment after puberty. Necessary extractions were performed, and she had full-arch treatment of the maxillary and mandibular anterior teeth. A series of archwires was used in a timely manner to create an adequate arch form and close the interdental spaces. Once treatment was completed, retention was ensured with a maxillary spring aligner and mandibular fixed retainer. RESULTS: Maxillary alignment and an adequate arch form were achieved, and mandibular treatment was limited to the anterior segment. The patient finished treatment with an esthetically pleasing smile. CONCLUSIONS: There have been few reports of orthodontic treatment for a patient with cherubism. This case report provides evidence that complete or limited orthodontic treatment can be provided to these patients to improve facial esthetics and bolster their self-esteem.

Familial cherubism: clinical and radiological features. Case report and review of the literature.

BACKGROUND: Cherubism is a rare genetic disorder that causes prominence in the lower portion in the face. The authors present the case of an 11-year old boy showing bilateral enlargement of the mandible. CASE REPORT: Computer tomography evidenced the presence of characteristic cherubism changes. The genetic test confirmed heterozygote mutation c.1244G>A (p.R415Q) in second exon coding sequence of SH3BP2 gene. Radiographic examinations performed on some close relatives of the patient revealed typical changes. The patient did not require any surgical treatment and the "wait and see" protocol was applied.

Clinical and genetic analysis of patients with cherubism.

OBJECTIVE: To describe the clinical and genetic features of patients with cherubism. MATERIAL AND METHODS: A descriptive analysis of 14 cases from nine different families was carried out. Clinicopathological, imaging, and follow-up data were retrieved from patients' medical files and correlated with the genetic profile of each patient. Genomic DNA isolated from buccal mucosa cells was subjected to direct sequencing analysis of the SH3BP2 gene. RESULTS: Females were more affected than males (8:6), and the mean age at diagnosis was 8.6 years (range 3-30 years). Eleven patients exhibited simultaneous bilateral involvement of the maxilla and mandible. Two patients did not have a familial history of cherubism. Progressive growth pattern was found in six patients and stable lesions were observed in other seven patients, whereas in one patient, complete spontaneous remission was documented during the follow-up (31 years). Mutations were found in 13 cases and included the typical heterozygous missense mutations R415Q, P418T, and P418H at exon 9 of SH3BP2. No correlation between the mutations and the clinical manifestations was observed. CONCLUSION: Three different point mutations in the SH3BP2 gene were detected with variable clinical involvement. Genotype-phenotype association studies in larger population with cherubism are necessary to provide important knowledge about molecular mechanisms related to the disease.

Cherubism: An Unusual Study With Long-Term Follow-Up.

Cherubism is an uncommon hereditary benign fibro-osseous disorder characterized by bilateral enlargement of the mandible and the maxilla that presents with varying degrees of involvement and a tendency toward spontaneous remission.The first visit was in 2002. A 16-year-old female was referred to an orthodontist for correction of her dental crowding. In the radiographic examination that was taken for her treatment the first time in 2002, a jaw bone lesion was discovered accidentally. X-ray panoramic imaging revealed well-defined multilocular radiolucencies involving the posterior body of the mandible and ascending rami with displaced teeth. This lesion had no effect on inferior alveolar canal and maxilla.There was no significant past medical history, and there was no family history suggestive of a similar complaint. On extraoral examination, there was no swelling in both rami of the mandible and face. Histopathological examination of the biopsy specimen showed proliferating fibrous connective tissue interspersed by multinucleated giant cells. It was diagnosed as a case nonfamilial cherubism. An extensive long-term follow-up till 12 years was maintained. In 2014, after 12-years follow-up for this lesion, panoramic imaging examination showed progress of this lesion in mandible and maxilla.

Cherubism With Bilateral Mandible and Maxilla Involvement: A Case Report.

Cherubism is a rare, nonneoplastic, self-limiting fibro-osseous that occurs in children. Affected children usually appear normal at birth. Lesions are characterized by the replacement of bone with fibrovascular tissue containing many multinucleated giant cells. Most studies have reported cherubism to be familial and with bilateral involvement of the mandibles. The authors describe a nonfamilial case of cherubism, involving both the mandible and the maxilla, in a 4-year-old female child with slowly enlarging, painless, symmetrical swelling of both cheeks.Cherubism is a rare disease that is usually limited to the mandible, but the maxilla may be involved. Computed tomography scan and biopsy are helpful for early diagnosis.

Late Reactivation of Cherubism in a Patient With New-Onset Polycystic Ovary Syndrome.

PURPOSE: The aim of the present study was to describe a case of cherubism with late progression, after skeletal maturity had been reached, that coincided with a recent diagnosis of polycystic ovary syndrome (PCOS). PATIENTS AND METHODS: We reviewed the published data and searched for any reported association between cherubism and PCOS. We also reviewed the cases of late reactivation of cherubism. RESULTS: This is, to our knowledge, the first case report of cherubism associated with PCOS. CONCLUSION: Cherubism is a rare condition, which, in its normal course, becomes quiescent after puberty. Only a few cases of late growth have been reported. The understanding of the condition has evolved in recent years, with a better appreciation of the underlying genetics and pathogenesis of the disease. However, much remains unknown about this rare entity. We describe a case of cherubism reactivation that coincided with changes related to PCOS. Both PCOS and cherubism are associated with a low-grade inflammatory state.

Recurrent cherubism in an adult patient.

Cherubism is an uncommon, nonneoplastic, fibro-osseous disorder of the jaws in childhood and adolescence. It affects the jaw bones by deforming the cortical shell. Clinical features include progressive painless and mostly bilateral expansion of the mandible and/or maxilla. Because fibrous connective tissue replaces osseous tissue, radiographic features generally include expansile osteolytic lesions and a ground-glass appearance. Several treatment protocols for cherubism have been recommended in the literature; however, despite surgical curettage treatment, recurrences may occur. Our aim was to emphasize the high recurrence rate of cherubic lesions. In this article, we present cherubism in a young girl that relapsed after 5 surgical operations before her appearance to our clinic.