Cherubism

What is Cherubism?

This rare disease is a genetic condition currently diagnosed in 200 individuals worldwide, to date.

Individuals with Cherubism have very distinct facial features.

The syndrome is believed to be two times more common in males than females.

Syndrome Synonyms:
Crbm

What gene changes cause Cherubism?

Changes in the SH3BP2 gene are responsible for the syndrome. The syndrome is inherited in an autosomal dominant pattern.

In the case of autosomal dominant inheritance just one parent is the carrier of the gene mutation, and they have a 50% chance of passing it onto each of their children. Syndromes inherited in an autosomal dominant inheritance are caused by just one copy of the gene mutation.

What are the main symptoms of Cherubism?

The main symptom of the syndrome is due to abnormal bone tissue in the jaw. Beginning in childhood the bone in the upper and lower jaws of affected individuals is replaced by painless, cyst like growths.
This growth usually stabilizes with the onset of puberty. It may also be mild to severe depending on the individual. Individuals with severe symptoms may also suffer from breathing and feeding difficulties due to these changes to the jaw.

Other symptoms of the condition may include upturned eyes, and premature loss of primary teeth.

Possible clinical traits/features:
Macular scar, Marcus Gunn pupil, Round face, Childhood onset, Reduced number of teeth, Proptosis, Autosomal dominant inheritance, Optic neuropathy, Oligodontia, Optic atrophy, Striae distensae, Visual impairment, Constriction of peripheral visual field, Feeding difficulties in infancy, Abnormality of dental morphology, Neoplasm of the skeletal system, Abnormality of the mandible, Abnormality of the voice, Apnea

How does someone get tested for Cherubism?

The initial testing for Cherubism syndrome can begin with facial analysis screening, through the FDNA Telehealth telegenetics platform, which can identify the key markers of the syndrome and outline the need for further testing. A consultation with a genetic counselor and then a geneticist will follow.

Based on this clinical consultation with a geneticist, the different options for genetic testing will be shared and consent will be sought for further testing.

Medical information on Cherubism

The earliest age of onset is 18 months and most cases present before the age of 7 years. There is a cystic swelling of the jaw which increases slowly until puberty, then regresses, although there might be radiological signs in adulthood. The palate is often V-shaped, the speech is indistinct and the face seems symmetrically swollen at the level of the mandible. Sub-mandibular lymphadenopathy is nearly always present. Missing (in some cases premature loss) and displaced teeth are common features (Prescott et al., 2013). Radiologically there are symmetrically placed, well defined, multilocular cysts or radiolucent areas, irregular in size, causing expansion of bone and thinning of the cortex. In adulthood the translucent areas are filled with a granular dense shadow and the jaw has normal contours. Stiller et al., (2000) reported a case associated with craniosynostosis. They suggested that FGFR3 may be a candidate gene. A case (confirmed by Bob Gorlin) had a cleft hand and Sprengel shoulder (Fleuchaus and Buhner, 1967). Some cases are particularly aggressive, with huge expansion (Wang et al., 2006).
Bob Gorlin has seen a case with an 18q duplication (personal communication). Al-Gazali et al., (1993) reported a case with optic atrophy and short stature. Quan et al., (1995) reported a male with mosaicism for an FMR1 expansion, and deletion of the CGG repeat, who also had Cherubism.
Mangion et al., (1999) mapped the gene to 4p16.3 in two dominant families. Tiziani et al., (1999) provided similar results from four families. Ueki et al., (2001) demonstrated mutations in the SH3BP2 gene. These appear to be gain of function.
Lo et al., (2003) found a G to A transition in exon 9 leading to a Gly to Arg substitution at amino acid position 420. G420R has been reported previously with a G to C transversion. The authors note that to date there have been no disease causing mutations outside exon 9 so that the amino acid sequence from positions 415 to 420 may represent a specific protein domain which, when disrupted, leads to the Cherubism phenotype. Jafarov et al., (2005) stressed that patients with Cherubism should be carefully evaluated for Noonan syndrome, as they found two PTPN11 mutations in patients with Cherubism, who had in retrospect, in fact, Noonan syndrome. Reduced penetrance was found in a Turkish family with a SH3BP2 mutation (de Lange et al., 2007). A mother (mild) and daughter (more severe) both had mutations (Preda et al., 2010).
Stoor et al. (2017) described craniofacial and dental features in six patients from three families with Cherubism. Clinical characteristics included Cherubism grade 2 or 3, premature loss of deciduous teeth, widely spaced, displaced and unerupted or absent permanent teeth, delayed dental age, expansive bilateral radiolucent soap-bubble-like cystic lesions, and osteosclerosis.

* This information is courtesy of the L M D.
If you find a mistake or would like to contribute additional information, please email us at: [email protected]

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