Cherubism is a disorder characterized by abnormal bone tissue in the jaw. Beginning in early childhood, both the lower jaw (the mandible) and the upper jaw (the maxilla) become enlarged as bone is replaced with painless, cyst-like growths. These growths give the cheeks a swollen, rounded appearance and often interfere with normal tooth development. In some people the condition is so mild that it may not be noticeable, while other cases are severe enough to cause problems with vision, breathing, speech, and swallowing. Enlargement of the jaw usually continues throughout childhood and stabilizes during puberty. The abnormal growths are gradually replaced with normal bone in early adulthood. As a result, many affected adults have a normal facial appearance.
Most people with cherubism have few, if any, signs and symptoms affecting other parts of the body. Rarely, however, this condition occurs as part of another genetic disorder. For example, cherubism can occur with Ramon syndrome, which also involves short stature, intellectual disability, and overgrowth of the gums (gingival fibrosis). Additionally, cherubism has been reported in rare cases of Noonan syndrome (a developmental disorder characterized by unusual facial characteristics, short stature, and heart defects) and fragile X syndrome (a condition primarily affecting males that causes learning disabilities and cognitive impairment).
The incidence of cherubism is unknown. At least 250 cases have been reported worldwide.
Mutations in the SH3BP2 gene have been identified in about 80 percent of people with cherubism. In most of the remaining cases, the genetic cause of the condition is unknown.
The SH3BP2 gene provides instructions for making a protein that plays a role in transmitting chemical signals within cells. the SH3BP2 protein is particularly important for the function of cells involved in the replacement of old bone tissue with new bone (bone remodeling) and certain immune system cells.
Mutations in the SH3BP2 gene lead to production of an abnormal protein that does not get broken down when it is no longer needed. Too much SH3BP2 protein likely increases signaling in certain cells, causing an immune reaction (inflammation) in the jaw bones and also triggering the production of osteoclasts, which are cells that break down bone tissue during bone remodeling. An excess of these bone-destroying 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.
When cherubism occurs as a feature of a genetic syndrome, it is caused by the same genetic alteration that causes the syndrome.
This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
5. Other Names for This Condition
Familial benign giant-cell tumor of the jaw
Familial fibrous dysplasia of jaw
Familial multilocular cystic disease of the jaws
The entry is from https://medlineplus.gov/genetics/condition/cherubism
- Carvalho Silva E, Carvalho Silva GC, Vieira TC. Cherubism: clinicoradiographicfeatures, treatment, and long-term follow-up of 8 cases. J Oral Maxillofac Surg. 2007 Mar;65(3):517-22.
- de Lange J, van Maarle MC, van den Akker HP, Redeker EJ. A new mutation in theSH3BP2 gene showing reduced penetrance in a family affected with cherubism. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007 Mar;103(3):378-81.
- Guettler S, LaRose J, Petsalaki E, Gish G, Scotter A, Pawson T, Rottapel R,Sicheri F. Structural basis and sequence rules for substrate recognition byTankyrase explain the basis for cherubism disease. Cell. 2011 Dec9;147(6):1340-54. doi: 10.1016/j.cell.2011.10.046. Erratum in: Cell. 2012 Jan20;148(1-2):376.
- Kannu P, Baskin B, Bowdin S. Cherubism. 2007 Feb 26 [updated 2018 Nov 21]. In:Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A,editors. GeneReviews® [Internet]. Seattle (WA): University of Washington,Seattle; 1993-2020. Available from http://www.ncbi.nlm.nih.gov/books/NBK1137/
- Levaot N, Voytyuk O, Dimitriou I, Sircoulomb F, Chandrakumar A, Deckert M,Krzyzanowski PM, Scotter A, Gu S, Janmohamed S, Cong F, Simoncic PD, Ueki Y, LaRose J, Rottapel R. Loss of Tankyrase-mediated destruction of 3BP2 is theunderlying pathogenic mechanism of cherubism. Cell. 2011 Dec 9;147(6):1324-39.doi: 10.1016/j.cell.2011.10.045.
- Lo B, Faiyaz-Ul-Haque M, Kennedy S, Aviv R, Tsui LC, Teebi AS. Novel mutation in the gene encoding c-Abl-binding protein SH3BP2 causes cherubism. Am J MedGenet A. 2003 Aug 15;121A(1):37-40.
- Novack DV, Faccio R. Jawing about TNF: new hope for cherubism. Cell. 2007 Jan 12;128(1):15-7.
- Ozkan Y, Varol A, Turker N, Aksakalli N, Basa S. Clinical and radiologicalevaluation of cherubism: a sporadic case report and review of the literature. IntJ Pediatr Otorhinolaryngol. 2003 Sep;67(9):1005-12. Review.
- Peñarrocha M, Bonet J, Mínguez JM, Bagán JV, Vera F, Mínguez I. Cherubism: aclinical, radiographic, and histopathologic comparison of 7 cases. J OralMaxillofac Surg. 2006 Jun;64(6):924-30.
- Ueki Y, Lin CY, Senoo M, Ebihara T, Agata N, Onji M, Saheki Y, Kawai T,Mukherjee PM, Reichenberger E, Olsen BR. Increased myeloid cell responses toM-CSF and RANKL cause bone loss and inflammation in SH3BP2 "cherubism" mice.Cell. 2007 Jan 12;128(1):71-83.
- Ueki Y, Tiziani V, Santanna C, Fukai N, Maulik C, Garfinkle J, Ninomiya C,doAmaral C, Peters H, Habal M, Rhee-Morris L, Doss JB, Kreiborg S, Olsen BR,Reichenberger E. Mutations in the gene encoding c-Abl-binding protein SH3BP2cause cherubism. Nat Genet. 2001 Jun;28(2):125-6.
- Von Wowern N. Cherubism: a 36-year long-term follow-up of 2 generations indifferent families and review of the literature. Oral Surg Oral Med Oral PatholOral Radiol Endod. 2000 Dec;90(6):765-72. Review.