In 1933, Jones first described familial occurrence of painless enlargement of the jaws in three siblings. Jones later in 1938 reported observations on the same family under the title “famil- ial multilocular cystic disease of the jaws” and coined the term
“cherubism” after the cherubs of Renaissance art for the full round cheeks and the upward cast of the eyes giving the chil- dren a peculiarly grotesque, cherubic appearance.
GENETICS/BASIC DEFECTS
1. Inheritance
a. Autosomal dominant b. Familial in 80% of cases
c. Males affected twice as often as females d. 80% overall penetrance
i. 100% in males ii. 50–70% in females e. Variable expressivity 2. Cause
a. Caused by mutations in the gene encoding c-Abl- binding protein SH3BP2
b. Gene for cherubism mapped to chromosome region 4p16.3
CLINICAL FEATURES
1. Variable size of the jaw lesions in cherubism a. Minor lesions of both jaws
b. Massive involvement of both jaws 2. Natural history:
a. Classically normal at birth
b. Onset usually between 14 months and 5 years.
However, the severe cases are evident at birth c. Progresses until puberty
d. Usually progression stops after puberty
e. Regression of the bone lesions (involution of the dis- ease) without treatment in some cases
f. Rapidly growing and extensively deforming lesions of the maxilla and the mandible including the coro- noids and condyles in severely affected individuals 3. Characteristic ‘eyes raised to heaven’ cherubic appearance:
an appearance of the cherubs portrayed in Renaissance art a. Fullness of the lower half of the face (cheeks and jaw) b. Retraction of the lower lids by the stretched skin over the cheeks pulling down the lower eyelids.
Consequently, a thin line of sclera is exposed beneath the iris and the eyes appear to be raised heavenward in a manner reminiscent of a “the cherubs in Renaissance paintings”
4. Painless hard enlargement of the jaws 5. Exclusively affecting maxilla and mandible
a. Mandible usually involved
b. Involvement of the maxilla in 60% of cases
c. Painless lesions
d. Bilateral enlargement with loss of bone in the jaws and its replacement with large amount of fibrous tissue e. Dental effect by bone lesion
i. Premature loss of deciduous teeth ii. Displacement of permanent dentition
f. Swelling usually abates by the third decade, whereas radiographic changes commonly persist into the fourth decade
6. Submandibular lymph node enlargement in 45% of cases 7. Ocular manifestations
a. Lower lid retraction b. Proptosis
c. Diplopia
d. Globe displacement
e. Visual loss due to optic nerve atrophy f. Rare extension of lesion into the orbits 8. Rare upper airway involvement
a. Displaced tongue affecting speech, mastication, swal- lowing, and respiration
b. Obstructive apnea
9. Extremely rare extrafacial skeletal involvement a. Upper humerus
b. Bilateral triquetral bones c. Anterior ribs
d. Upper femoral necks 10. Rare associated syndromes
a. Noonan syndrome (Addante, 1996) b. Ramon syndrome
i. Cherubism ii. Short stature iii. Mental retardation
iv. Gingival fibromatosis v. Epilepsy
c. Fragile X syndrome d. Craniosynostosis 11. Functional impairment
a. Mastication problems b. Speech difficulty c. Tooth alteration d. Loss of normal vision 12. Psychological consequences 13. Differential diagnosis
a. Four main types of fibrous dysplasia
i. Monostotic fibrous dysplasia: only one bone is affected
ii. Polyostotic: multiple bones are affected iii. McCune-Albright syndrome
a) Polyostotic form
b) Accompanied by pigmentary lesions c) Endocrine dysfunction presenting as preco-
cious puberty in females
iv. Craniofacial form of fibrous dysplasia 153
Cherubism
154 CHERUBISM
a) Only bones of the craniofacial complex are affected
b) Onset in the second decade in majority of patients
c) Generally unilateral lesions, tend to become static once skeletal maturity is reached d) Clinically difficult to differentiate from
cherubism if the skeletal abnormalities are localized to the jaws
e) Molecularly different from cherubism b. Infantile cortical hyperostosis
i. Diagnosed in the first 6 months of life
ii. Radiographically does not produce cystic areas iii. Characterized by thickening of the mandibular
lower border
iv. Does not have bilateral expression
c. Osteitis fibrosa cystica secondary to hyperparathy- roidism
i. Increased serum alkaline phosphatase ii. Increased serum calcium
iii. Decreased serum phosphorus iv. Increased urinary phosphorus d. Various tumors of the jaws
DIAGNOSTIC INVESTIGATIONS
1. Serum alkaline phosphatase levels may be elevated 2. Radiography
a. Extensive involvement of the mandible and the maxilla b. Multilocular radiolucent areas in the mandible and
maxilla with expansion of the bony cortex i. Often very extensive
ii. With a few irregular bony septa
iii. Multilocular rarefactions replaced by sclerosis with progressive calcification in the adult c. Absent and displaced teeth in the involved areas 3. CT scan
a. Superior in making the diagnosis b. Determining the degree of severity 4. Histological changes in cherubism
a. Replacement of the normal bony architecture with pro- liferating fibrous tissue containing numerous giant cells b. Mononuclear fibroblastic stroma
i. Nonneoplastic fibrous lesions rich in multinucle- ated giant cells identified as osteoclasts
ii. Irregular bone formation
c. A peculiar perivascular cuffing of collagen: consid- ered by some to be pathognomonic for the condition d. Histological resemblance to the following disorders:
i. Giant cell tumor ii. Giant cell granulomas iii. Ossifying fibroma
iv. Fibrous dysplasia of the jaw v. Paget disease of bone
5. Molecular genetic analysis: detection of a SH3BP2 gene mutation by sequencing of select exons or entire coding region is available clinically
GENETIC COUNSELING
1. Recurrence risk
a. Patient’s sib: not increased unless a parent is affected b. Patient’s offspring: 50%
2. Prenatal diagnosis
a. Ultrasonography: not possible since the lesion is post- natal in nature
b. Molecular analysis possible on fetal DNA obtained by amniocentesis or CVS if the disease-causing muta- tion is identified in an affected family member 3. Management
a. Observation
i. Generally self-limiting lesions and subside with age
ii. Surgical intervention required only in cases with esthetic or functional problems
b. Tracheostomy to secure the airway for upper airway obstruction
c. Teeth extraction from the sites of fibrous changes d. Curettage alone or in combination with surgical con-
touring: considered the treatment of choice
e. Resection of the orbital lesions may be required to improve visual impairment
f. Prompt recurrence likely if surgery is performed at an early age
g. Radiation therapy ineffective and contraindicated in view of the following risks:
i. Osteoradionecrosis
ii. Interference with dentofacial growth and devel- opment
iii. Affect on future surgical procedures
h. Experimental use of calcitonin to treat cherubism described recently
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156 CHERUBISM
Fig. 1. A boy with cherubism showing full cheeks and jaw and the retraction of the lower eyelids with symmetrical augmentation on both mandibular angles.
