Cherubism

Cherubism is a rare genetic disorder of the jaw characterized by bilateral, symmetrical enlargement of the mandible and/or maxilla resulting from rapid bone degradation followed by extensive bone remodeling with multilocular benign cysts. As a consequence, the skin is stretched over the classically swollen cheeks, pulling the lower eyelids down and exposing a line of sclera so that the eyes appear to be “raised heavenward.” This facial appearance of the upwardly turning eyes and swollen cheeks has been described as resembling the faces of cherubs found in Renaissance art. The variable cherubism phenotype can range from absence of any clinical features to severe mandibular and maxillary overgrowth causing respiratory, vision, speech, and swallowing concerns. Typical age of onset is 2 to 5 years, with the jaw lesions progressing gradually until puberty when the swelling spontaneously stabilizes and then regresses. Residual radiographic changes can last into the fourth decade. Associated dental abnormalities may include congenitally missing teeth, premature loss of the deciduous teeth, and displacement of the permanent teeth by jaw lesions. While the disease is usually restricted to the jaw, rare cases of radiological abnormalities of the ribs have been reported. The differential diagnosis for Cherubism includes Noonan-like/Multiple giant-cell lesion syndrome, Central giant-cell granuloma, Fibrous dysplasia of the jaw, and Hyperparathyroidism. Mutations in the PTPN11 gene have been described in association with both familial and isolated Noonan-like/Multiple giant-cell lesion syndrome. Cherubism can be distinguished from the other conditions on the basis of clinical, radiologic, and biochemical evaluation. Finally, Cherubism has been reported as one of the clinical features of Ramon syndrome (characterized by short stature, mental retardation, and gingival fibromatosis), and also can be associated with Neurofibromatosis Type 1.

Tests Available

Forms and Documents

Test Details

SH3BP2
  • Confirmation of a clinical diagnosis
  • To differentiate Cherubism from other disorders with cystic jaw lesions (as described above)
  • Risk assessment
  • Prenatal diagnosis in families with an affected child and known mutation
  • Capillary Sequencing

Ordering

285
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 526.89 Other Cherubism Fibrous dysplasia of jaw(s), Latent bone cyst of jaw(s), Osteoradionecrosis of jaw(s), Unilateral condylar hyperplasia or hypoplasia of mandible
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References

  1. Pina-Nito, J.M. et al. Cherubism, gingival fibromatosis, epilepsy, and mental deficiency (Ramon syndrome) with juvenile rheumatoid arthritis. Am J Med Genet. 25: 433-41, 1986
  2. van Capelle, C.I. et al. Neurofibromatosis presenting with a cherubism phenotype. Eur J Pediatr. 166: 905-9, 2007
  3. Martinez-Tello, F.J. et al. Cherubism associated with neurofibromatosis type 1, and multiple osteolytic lesions of both femurs: a previously undescribed association of findings. Skeletal Radiol. 34: 793-8, 2005
  4. Anderson, D.E. and McClendon J.L., Cherubismhereditary fibrous dysplasia of the jaws; I genetic considerations. Oral Surg Oral Med Oral Pathol. 15 Suppl 2: 5- 16, 1962
  5. Peters, W.J., Cherubism: a study of twenty cases from one family. Oral Surg Oral Med Oral Pathol. 47: 307-11, 1979
  6. Lietman, S.A. et al., Identification of a Novel Mutation of SH3BP2 in Cherubism and Demonstration that SH3BP2 Mutations Lead to Increased BFAT Activation. Hum Mutat. 27:717-8, 2006
  7. Ueki, Y. et al., Mutations in the gene encoding c-Abl-binding protein SH3BP2 cause cherubism. Nat Genet. 28:125-125, 2001
  8. de Lange, J. et al., A new mutation in the SH3BP2 gene showing reduced penetrance in a family affected with cherubism. Oral Surg Oral Med Oral Path Oral Radiol Endod. 103:378-81, 2007
  9. Li, Cui Ying and Yu, Shi Feng, A novel mutation in the SH3BP2 gene causes cherubism: case report BMC Med Genet. 7: 84, 2006
  10. Imai, Y. et al., A Missense Mutation in the SH3BP2 Gene on Chromosome 4p16.3 Found in a Case of Nonfamilial Cherubism. Cleft Palate Craniofac J. 40:632-8, 2003
  11. Lo, B. et al., Novel mutation in the gene encoding c-Abl binding protein SH3BP2 causes cherubism. Am J Med Genet A. 121:37-40, 2003