(6 intermediate revisions by the same user not shown)
Line 1:
Line 1:
{{Infobox medical condition (new)
{{SI}}
{{Infobox medical condition
| name = Cherubism
| name = Cherubism
| synonyms =
| image = [[File:Cherubism2.jpg]]
| image = Cherubism2.jpg
| caption = Facial appearance of a child with cherubism
| width = 220
| field = [[Genetics]]
| caption = Three-dimensional [[computed tomography]] of a 41-year-old Chinese woman diagnosed with cherubism shows a remarkable expansion of the mandible, which can lead to a soap bubble appearance, and the bilateral bulges of the maxilla
| synonyms = Familial fibrous dysplasia of the jaws
| pronounce =
| symptoms = Painless swelling of the [[jaw]], rounded face
| treatment = Monitoring, [[surgery]] if necessary
| diagnosis =
| prognosis = Generally good, condition often stabilizes
| differential =
| frequency = Rare
| prevention =
| treatment =
| medication =
| prognosis =
| frequency =
| deaths =
}}
}}
'''Cherubism''' is a rare genetic disorder that causes prominence in the lower portion in the face. The name is derived from the temporary chubby-cheeked resemblance to [[putto|putti]], often confused with [[cherub]]s, in [[Renaissance painting]]s.
Cherubism
[[File:Cherubism2.jpg|left|thumb|A child with cherubism, showing characteristic facial swelling.]]
==Signs and symptoms==
'''Cherubism''' is a rare genetic disorder that affects the bones of the face, particularly the jawbones. It is characterized by painless, progressive swelling of the cheeks and jaw, giving the affected individuals a cherubic appearance, hence the name.
The appearance of people with the disorder is caused by a loss of bone in the [[mandible]] which the body replaces with excessive amounts of [[fibrous tissue]]. In most cases, the condition fades as the child grows, but in a few even rarer cases the condition continues to deform the affected person's face. Cherubism also causes premature loss of the [[primary teeth]] and uneruption of the [[permanent teeth]].
==Etiology==
Cherubism is caused by mutations in the [[SH3BP2]] gene, which is located on chromosome 4. This gene is responsible for producing a protein involved in the regulation of bone metabolism. The mutation leads to abnormal bone remodeling, resulting in the characteristic facial features of the disorder.
Cherubism is a rare [[autosomal dominant]] disease of the [[maxilla]] and mandible. Approximately 200 cases have been reported by medical journals with the majority being males. Cherubism is usually first diagnosed around age 7 and continues through puberty and may or may not continue to advance with age.<ref name=Sullivan>{{cite journal |vauthors=Carroll AL, Sullivan TJ |title=Orbital involvement in cherubism |journal=Clin. Experiment. Ophthalmol. |volume=29 |issue=1 |pages=38–40 |date=February 2001 |pmid=11272784 |doi=10.1046/j.1442-9071.2001.00363.x}}</ref> Degrees of cherubism vary from mild to severe. [[Osteoclast]]ic and [[osteoblastic]] [[Bone remodeling|remodeling]] contributes to the change of normal bone to fibrous tissue and [[cyst]] formation. As noted by the name, the patient's face becomes enlarged and disproportionate due to the fibrous tissue and atypical bone formation. The sponge-like bone formations lead to early tooth loss and permanent tooth eruption problems. The condition also affects the [[orbital area]], creating an upturned eye appearance. The cause of cherubism is believed to be traced to a genetic defect resulting from a [[mutation]] of the [[SH3BP2]] gene from [[Chromosome 4 (human)|chromosome 4p16.3]].<ref name=Cui-Ying>{{cite journal |vauthors=Li CY, Yu SF |title=A novel mutation in the SH3BP2 gene causes cherubism: case report |journal=BMC Med. Genet. |volume=7 |pages=84 |year=2006 |pmid=17147794 |pmc=1764878 |doi=10.1186/1471-2350-7-84 }}</ref> While the condition 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, removal of the tissue and bone by surgery is the only treatment available. This condition is also one of the few that unexpectedly stops and regresses.<ref name=Tiziani>{{cite journal |vauthors=Tiziani V, Reichenberger E, Buzzo CL |title=The gene for cherubism maps to chromosome 4p16 |journal=American Journal of Human Genetics |volume=65 |issue=1 |pages=158–166 |date=July 1999 |pmid=10364528 |pmc=1378086 |doi=10.1086/302456 |display-authors=etal}}</ref> Normal bone remodeling activity may resume after puberty.
==Clinical Features==
The primary clinical feature of cherubism is bilateral swelling of the cheeks due to the overgrowth of the jawbones. This typically becomes apparent in early childhood, around the age of 2 to 7 years. The condition progresses until puberty, after which it often stabilizes or regresses.
Cherubism is displayed with genetic conformation and when excessive osteoclasts are found in the affected areas of the mandible and maxilla. Large cysts will be present with excessive fibrous areas inside the bone. The fibers and cysts will be found among the [[trabecula]] of the [[Coronoid process of the mandible|Coronoid process]], the [[Ramus of the mandible|ramus]] of mandible, the [[body of mandible]] and the maxilla regions. The maxilla will be affected up to and including the [[Orbit (anatomy)|orbits]] and sometimes inside the lower orbits.<ref name=Irfan>{{cite journal |vauthors=Irfan S, Cassels-Brown A, Hayward J, Corrigan A |title=Orbital Cherubism |journal=Orbit |volume=16 |issue=2 |pages=109–112 |year=1997 |doi=10.3109/01676839709019125}}</ref> The maxilla and zygomatic bones are depressed and eyes appear to gaze upward.<ref name=Emoto>{{cite journal |vauthors=Emoto Y, Emoto H, Fujle W, Wakakura M |title=Uncorrectable Oblique Astigmatism and Impaired Binocular Vision in Case of Orbital Cherubism |journal=Neuro-ophthalmology |volume=31 |issue=5–6 |pages=191–195 |year=2007 |doi=10.1080/01658100701648553}}</ref> The maxilla has been found to be more severely affected in most cases than the mandible bone. Some patients found with lower inner orbital growths and cysts may lose vision.
Other features may include:
* [[Dental abnormalities]], such as malocclusion, displacement of teeth, and delayed eruption.
== Causes ==
* [[Ocular]] issues, such as upward displacement of the eyes, giving a "heavenward gaze" appearance.
Cherubism is [[autosomal dominant]]ly linked. Cherubism has also been found from the random mutation of a gene in an individual having no family history of the condition. However it is not well understood why males tend to express the disease more frequently. Children with cherubism vary in severity in their maxilla and mandible bony [[lesions]]. The disease is expressed at a rate of 80 to 100% of all affected. Studies of multiple generations of families with the gene found that all boys developed cherubism, but 30–50% of girls show no symptoms.<ref>{{cite web|title=About Cherubism|website=FibrousDysplasia.org|publisher=Fibrous Dysplasia Foundation|url=https://www.fibrousdysplasia.org/disease-information/about-cherubism/|accessdate=5 November 2017|ref=FDF}}</ref>
* In some cases, [[hearing loss]] due to involvement of the bones surrounding the ear.
==Pathophysiology==
The cause of cherubism is believed to be from a [[mutation]] of gene of [[SH3BP2]]. Cherubism has also been found combined with other genetic disorders including [[Noonan syndrome]], [[Ramon syndrome]], and [[fragile X syndrome]].<ref name="VanCapelle">{{cite journal |vauthors=van Capelle CI, Hogeman PH, van der Sijs-Bos CJ |title=Neurofibromatosis presenting with a cherubism phenotype |journal=European Journal of Pediatrics |volume=166 |issue=9 |pages=905–9 |date=September 2007 |pmid=17120035 |doi=10.1007/s00431-006-0334-6 |display-authors=etal}}</ref> Mutations of the SH3BP2 gene are only reported in 75% of Cherubism cases.<ref name="Cui-Ying" /> The mutation of the SH3BP2 gene is believed to increase production of over active proteins from this gene. The SH3BP2 gene is found on the smaller arm of chromosome 4 at position 16.3.<ref name="Cui-Ying" /> The SH3BP2 protein is involved with chemical signaling to [[immune system]] cells known as [[macrophages]] and [[B cells]].
The pathophysiology of cherubism involves the replacement of normal bone with fibrous tissue and cyst-like structures. This process is driven by the abnormal activity of osteoclasts and osteoblasts, which are cells responsible for bone resorption and formation, respectively.
The effects of SH3BP2 mutations are still under study, but researchers believe that the abnormal protein disrupts critical signaling pathways in cells associated with the maintenance of bone tissue and in some immune system cells. The overactive protein likely causes [[inflammation]] in the jaw bones and triggers the production of [[osteoclasts]], which are cells that break down bone tissue during [[bone remodeling]]. Osteoclasts also sense the increased inflammation of the mandible and maxilla and are further activated to break down bone structures. Bone loss and inflammation lead to increased [[fibrous tissue]] and cyst growth. An excess of these bone-eating cells contributes to the destruction of bone in the upper and lower jaws. A combination of bone loss and inflammation likely underlies the cyst-like growths characteristic of cherubism.
==Diagnosis==
==Diagnosis==
The chemical imbalance is usually diagnosed when dental abnormalities are found. These abnormalities include premature deciduous teeth and abnormal growth of permanent teeth due to displacement by cysts and lesions. The only definite way to correctly diagnose the condition is by [[sequence analysis]] of the SH3BP2 gene. The gene has been found to have [[missense mutation]] in exon 9.<ref name=Tiziani/> Initial study of the patient is usually conducted using [[x-ray]] and [[CT scans]]. [[Neurofibromatosis]] may resemble cherubism and may accompany the condition. Genetic testing is the final diagnosis tool.
Diagnosis of cherubism is primarily clinical, based on the characteristic facial appearance and family history. [[Radiographic imaging]] of the jaws reveals multilocular radiolucencies, often described as "soap bubble" or "honeycomb" appearances. Genetic testing can confirm the diagnosis by identifying mutations in the SH3BP2 gene.
==Management==
== Prevention ==
Management of cherubism is largely supportive and symptomatic. Regular dental care is essential to address dental issues. In some cases, surgical intervention may be necessary to correct severe deformities or functional impairments. The condition often stabilizes or improves after puberty, reducing the need for aggressive treatment.
Because this genetic anomaly is genetically linked, [[genetic counseling]] may be the only way to decrease occurrences of cherubism. The lack of severe symptoms in the parents may be the cause of failure in recognizing the disorder. The optimal time to be tested for mutations is prior to having children. The disorder results from a genetic mutation, and this gene has been found to spontaneously mutate. Therefore, there may be no prevention techniques available.
==Prognosis==
The prognosis for individuals with cherubism is generally good. The facial swelling often regresses after puberty, and many individuals experience significant improvement in appearance. However, dental and skeletal issues may persist and require ongoing management.
==Treatment==
Because cherubism changes and improves over time, the treatment should be individually determined. Generally, moderate cases are watched until they subside or progress into the more severe range. Severe cases may require surgery to eliminate bulk cysts and fibrous growth of the maxilla and mandible. Surgical [[bone grafting]] of the [[Facial skeleton|cranial facial bones]] may be successful on some patients. Surgery is preferred for patients aged 5 to 15.<ref name=Sullivan/> Special consideration should be taken when operating on the face to avoid the [[Marginal mandibular branch of the facial nerve|marginal mandibular branch]] of the facial nerve as well as the [[Zygomatic branches of the facial nerve|zygomatic branch]] of the facial nerve. Unintentional damage to these nerves can decrease muscle strength in the face and mandible region. [[Orthodontic]] treatment is generally required to avoid permanent dental problems arising from [[Malocclusion|malocclusive]] bite and misplaced and unerupted permanent teeth.<ref name=Sullivan/> Orthodontic treatment may be used to erupt permanent teeth that have been unable to descend due to lesions and cysts being in their path of eruption. Patients with orbital issues of [[diplopia]], [[eye proptosis]], and visual loss will require [[ophthalmologic]] treatment.<ref name=Sullivan/>
== Prognosis ==
Due to the rarity of the condition, it is difficult to reliably estimate statistics. However, a 2006 study which followed 7 cases over an average of 8.5 years noted that "In general, cherubism does not have a poor prognosis. It has been noted that the condition does not progress beyond puberty. As the patient grows to adulthood, the jawbone lesions tend to resolve, and a progressively more normal jaw configuration is noted."<ref>{{Cite journal|last=Peñarrocha|first=Miguel|last2=Bonet|first2=Jaime|last3=Mínguez|first3=Juan Manuel|last4=Bagán|first4=José Vicente|last5=Vera|first5=Francisco|last6=Mínguez|first6=Ignacio|date=2006-06-01|title=Cherubism: a clinical, radiographic, and histopathologic comparison of 7 cases|journal=Journal of Oral and Maxillofacial Surgery|volume=64|issue=6|pages=924–930|doi=10.1016/j.joms.2006.02.003|issn=0278-2391|pmid=16713807}}</ref>
==History==
Cherubism was first documented and named in 1933 by Dr. W. A. Jones of [[Kingston, Ontario]], describing a case of three siblings of the same family of [[Jewish Russian]] heritage. All that was known at the time was the characteristic swelling pattern and the increase and then regress of bone [[lesions]].<ref>{{Cite journal | last1 = Jones | first1 = W. A. | title = Familial Multilocular Cystic Disease of the Jaws | doi = 10.1158/ajc.1933.946 | journal = The American Journal of Cancer | volume = 17 | issue = 4 | pages = 946–950 | year = 1933 | pmid = | pmc = }}</ref> By the time the children reached the ages of fifteen, sixteen, and seventeen, the facial deformity had become an obvious disfigurement and in 1943, the children were operated on by the Jones medical team, reducing the hard swelling of their jaws. Four years following the surgeries, there was no reappearance of the swellings.<ref>{{Cite journal | last1 = Jones | first1 = W. A. | last2 = Gerrie | first2 = J. | last3 = Pritchard | first3 = J. | title = Cherubism--familial fibrous dysplasia of the jaws | journal = The Journal of Bone and Joint Surgery. British Volume | volume = 32-B | issue = 3 | pages = 334–347 | year = 1950 | pmid = 14778852| doi = 10.1302/0301-620X.32B3.334 }}</ref> Yet, in some cases dysplasia reocurred after surgery, necessitating additional surgeries.{{citation needed|date=July 2019}}
==See also==
==See also==
* [[Fibrous dysplasia]]
* [[Fibrous dysplasia]]
* [[Robert Z'Dar]]
* [[Genetic disorders]]
* [[Osteoclast]]
==References==
* [[Osteoblast]]
{{Reflist}}
{{Genetic disorders}}
[[Category:Genetic disorders]]
==Further reading==
*{{cite web|title=Library of Published Research - Cherubism|url=https://www.fibrousdysplasia.org/research/research-library/#cherubismclinical|website=FibrousDysplasia.org|publisher=Fibrous Dysplasia Foundation|accessdate=16 September 2017}} Collection of research papers as PDFs
*National Library of Medicine. [http://ghr.nlm.nih.gov/condition=cherubism?wf=1 Cherubism]
*[https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=cherubism GeneReviews/NIH/UW entry on Cherubism]
*{{cite journal | pmid = 18811755 | doi=10.1111/j.1440-1673.2008.01963.x | volume=52 | issue=4 | title=Imaging of craniofacial fibrous dysplasia | date=August 2008 |vauthors=Lisle DA, Monsour PA, Maskiell CD | journal=J Med Imaging Radiat Oncol | pages=325–32}}
A child with cherubism, showing characteristic facial swelling.
Cherubism is a rare genetic disorder that affects the bones of the face, particularly the jawbones. It is characterized by painless, progressive swelling of the cheeks and jaw, giving the affected individuals a cherubic appearance, hence the name.
Cherubism is caused by mutations in the SH3BP2 gene, which is located on chromosome 4. This gene is responsible for producing a protein involved in the regulation of bone metabolism. The mutation leads to abnormal bone remodeling, resulting in the characteristic facial features of the disorder.
The primary clinical feature of cherubism is bilateral swelling of the cheeks due to the overgrowth of the jawbones. This typically becomes apparent in early childhood, around the age of 2 to 7 years. The condition progresses until puberty, after which it often stabilizes or regresses.
Other features may include:
Dental abnormalities, such as malocclusion, displacement of teeth, and delayed eruption.
Ocular issues, such as upward displacement of the eyes, giving a "heavenward gaze" appearance.
In some cases, hearing loss due to involvement of the bones surrounding the ear.
The pathophysiology of cherubism involves the replacement of normal bone with fibrous tissue and cyst-like structures. This process is driven by the abnormal activity of osteoclasts and osteoblasts, which are cells responsible for bone resorption and formation, respectively.
Diagnosis of cherubism is primarily clinical, based on the characteristic facial appearance and family history. Radiographic imaging of the jaws reveals multilocular radiolucencies, often described as "soap bubble" or "honeycomb" appearances. Genetic testing can confirm the diagnosis by identifying mutations in the SH3BP2 gene.
Management of cherubism is largely supportive and symptomatic. Regular dental care is essential to address dental issues. In some cases, surgical intervention may be necessary to correct severe deformities or functional impairments. The condition often stabilizes or improves after puberty, reducing the need for aggressive treatment.
The prognosis for individuals with cherubism is generally good. The facial swelling often regresses after puberty, and many individuals experience significant improvement in appearance. However, dental and skeletal issues may persist and require ongoing management.
