TEXT Jones first described Cherubism in 1933. This genetic dysfunction is only apparent, for the most part, in children ages two to five and begins to regress at puberty. Cherubism is characterized by the cherubic appearance in the facial area. This is associated with the cherubs from the Renaissance period. As described by J. Mangion, Cherubism is “proliferated lesions within the mandible and maxilla leading to prominence of the lower face and appearances reminiscent of Renaissance cherubs.” Gonjiro Hitomi says, “Cherubism is a nonneoplastic disease of bone characterized by clinical, bilateral, painless enlargements of the jaws that are said to give the patient a cherubic appearance.”
Cherubism can only be diagnosed after carefully reviewing many factors. The following comes from an article by J. J. Hille; “diagnosis of the giant cell lesion of the jaws can only be made after full consideration of the clinical, familial, radiological and histopathological features.” This supports the fact that the disease is genetic. It shows the familial evaluation that must be done in order for a diagnosis. Cherubism usually affects more than one member of an immediate family and throughout the generations as well.
Treatment for the disease is rarely needed. As stated before, the bone lesions start to regress during puberty. So, there is no need to surgically deter the disease unless the child is experiencing serious pain or there are other medical reasons to treat. From an article by O. Taskin Yucel, reasons for treatment may include, “. . . the disease deteriorates respiration, deglutition, vision, or the psychiatric makeup of the child due to cosmetic reasons.” Unless the child is suffering there should be nothing that has to be done. The child should be able to grow and function normally with no limitations due to the disease.
Cherubism is an autosomal dominant disorder of a gene. The gene has been mapped to the 4p16.3 chromosome through a genome wide search with a three-generation family, plus others. All members studied were narrowed to the same mutated locus. The combined LOD score is 4.21 at a recombination fraction of 0, and the locus has an interval of about 22-cM. However, the exact gene is not for certain. There is a probable hypothesis that the gene exists in a 3-cM interval between D4S127 and 4p-telomere. It is believed that the gene is the same as that which codes for fibroblast growth factor receptor 3. The gene is referred to as FGFR3. This gene affects bone development which, as discussed earlier, fits the description of Cherubism. Cherubism is the malformation of the mandible and maxilla during childhood and regression of the same characteristics later in life.
There is also a record showing that the gene affected is the FMR1 gene. This is the gene affected with fragile X syndrome which is a close companion to Cherubism. Since there was no gene map found for Cherubism a map of the FMR1 gene is included.
The following is the amino acid sequence for the FMR 1 gene
The following is the cDNA for the FMR1 gene.
Gene symbol: FMR1 Location: Xq27.3 Based on GenBank accession number: X69962.1 ------------------------------- HGMD CARDIFF ------------------------------ 1 ATG GAG GAG CTG GTG GTG GAA GTG CGG GGC TCC AAT GGC GCT TTC 15 16 TAC AAG GCA TTT GTA AAG GAT GTT CAT GAA GAT TCA ATA ACA GTT 30 31 GCA TTT GAA AAC AAC TGG CAG CCT GAT AGG CAG ATT CCA TTT CAT 45 46 GAT GTC AGA TTC CCA CCT CCT GTA GGT TAT AAT AAA GAT ATA AAT 60 61 GAA AGT GAT GAA GTT GAG GTG TAT TCC AGA GCA AAT GAA AAA GAG 75 76 CCT TGC TGT TGG TGG TTA GCT AAA GTG AGG ATG ATA AAG GGT GAG 90 91 TTT TAT GTG ATA GAA TAT GCA GCA TGT GAT GCA ACT TAC AAT GAA 105 106 ATT GTC ACA ATT GAA CGT CTA AGA TCT GTT AAT CCC AAC AAA CCT 120 121 GCC ACA AAA GAT ACT TTC CAT AAG ATC AAG CTG GAT GTG CCA GAA 135 136 GAC TTA CGG CAA ATG TGT GCC AAA GAG GCG GCA CAT AAG GAT TTT 150 151 AAA AAG GCA GTT GGT GCC TTT TCT GTA ACT TAT GAT CCA GAA AAT 165 166 TAT CAG CTT GTC ATT TTG TCC ATC AAT GAA GTC ACC TCA AAG CGA 180 181 GCA CAT ATG CTG ATT GAC ATG CAC TTT CGG AGT CTG CGC ACT AAG 195 196 TTG TCT CTG ATA ATG AGA AAT GAA GAA GCT AGT AAG CAG CTG GAG 210 211 AGT TCA AGG CAG CTT GCC TCG AGA TTT CAT GAA CAG TTT ATC GTA 225 226 AGA GAA GAT CTG ATG GGT CTA GCT ATT GGT ACT CAT GGT GCT AAT 240 241 ATT CAG CAA GCT AGA AAA GTA CCT GGG GTC ACT GCT ATT GAT CTA 255 256 GAT GAA GAT ACC TGC ACA TTT CAT ATT TAT GGA GAG GAT CAG GAT 270 271 GCA GTG AAA AAA GCT AGA AGC TTT CTC GAA TTT GCT GAA GAT GTA 285 286 ATA CAA GTT CCA AGG AAC TTA GTA GGC AAA GTA ATA GGA AAA AAT 300 301 GGA AAG CTG ATT CAG GAG ATT GTG GAC AAG TCA GGA GTT GTG AGG 315 316 GTG AGG ATT GAG GCT GAA AAT GAG AAA AAT GTT CCA CAA GAA GAG 330 331 GAA ATT ATG CCA CCA AAT TCC CTT CCT TCC AAT AAT TCA AGG GTT 345 346 GGA CCT AAT GCC CCA GAA GAA AAA AAA CAT TTA GAT ATA AAG GAA 360 361 AAC AGC ACC CAT TTT TCT CAA CCT AAC AGT ACA AAA GTC CAG AGG 375 376 GTG TTA GTG GCT TCA TCA GTT GTA GCA GGG GAA TCC CAG AAA CCT 390 391 GAA CTC AAG GCT TGG CAG GGT ATG GTA CCA TTT GTT TTT GTG GGA 405 406 ACA AAG GAC AGC ATC GCT AAT GCC ACT GTT CTT TTG GAT TAT CAC 420 421 CTG AAC TAT TTA AAG GAA GTA GAC CAG TTG CGT TTG GAG AGA TTA 435 436 CAA ATT GAT GAG CAG TTG CGA CAG ATT GGA GCT AGT TCT AGA CCA 450 451 CCA CCA AAT CGT ACA GAT AAG GAA AAA AGC TAT GTG ACT GAT GAT 465 466 GGT CAA GGA ATG GGT CGA GGT AGT AGA CCT TAC AGA AAT AGG GGG 480 481 CAC GGC AGA CGC GGT CCT GGA TAT ACT TCA GGA ACT AAT TCT GAA 495 496 GCA TCA AAT GCT TCT GAA ACA GAA TCT GAC CAC AGA GAC GAA CTC 510 511 AGT GAT TGG TCA TTA GCT CCA ACA GAG GAA GAG AGG GAG AGC TTC 525 526 CTG CGC AGA GGA GAC GGA CGG CGG CGT GGA GGG GGA GGA AGA GGA 540 541 CAA GGA GGA AGA GGA CGT GGA GGA GGC TTC AAA GGA AAC GAC GAT 555 556 CAC TCC CGA ACA GAT AAT CGT CCA CGT AAT CCA AGA GAG GCT AAA 570 571 GGA AGA ACA ACA GAT GGA TCC CTT CAG ATC AGA GTT GAC TGC AAT 585 586 AAT GAA AGG AGT GTC CAC ACT AAA ACA TTA CAG AAT ACC TCC AGT 600 601 GAA GGT AGT CGG CTG CGC ACG GGT AAA GAT CGT AAC CAG AAG AAA 615 616 GAG AAG CCA GAC AGC GTG GAT GGT CAG CAA CCA CTC GTG AAT GGA 630 631 GTA CCC TAA
The gene for has not been totally defined. It is believed that the FMR1 gene that is associated with Fragile X Syndrome is the same gene that affects the mandible of children.
Cherubism is detected by appearance first. There are also radiological tests that can be performed to detect the cell lesions on the jawbone. As for the treatment of Cherubism there really is none since the malformations begin to digress after puberty. The bones can be scraped down surgically however if the child is experiencing pain of any sort.