Chrubism

Cherubism¹

What kind of disease it is

Cherubism（家族性巨颌症） is a rare genetic disorder that primarily affects the jaws and face. It’s characterized by progressive, painless, bilateral swelling of the lower and sometimes upper jaw, giving the cheeks a rounded, "cherubic" appearance, hence the name.

Here’s a breakdown of what kind of disease Cherubism is:

1. Genetic Disorder:

• Inherited: Cherubism is caused by a mutation in a specific gene, most commonly the SH3BP2 gene.
• Autosomal Dominant: It’s typically inherited in an autosomal dominant pattern. This means that only one copy of the mutated gene from one parent is enough to cause the disorder. In some cases, it can also arise from a new spontaneous mutation.

2. Fibro-osseous Lesion:

• Bone Tissue Replacement: At its core, Cherubism involves the abnormal development of bone tissue in the jaws. Normal bone is replaced by fibrous tissue and cyst-like spaces. This process is driven by an overactive inflammatory response related to the mutated gene.
• Benign (Non-Cancerous): Importantly, Cherubism is not cancerous. It’s a benign condition, meaning it doesn’t spread to other parts of the body or become life-threatening in that way. However, its effects on facial structure and function can be significant.

3. Developmental Disorder:

• Age-Related Progression: Cherubism typically manifests in early childhood, usually between the ages of 2 and 5.
• Progressive Swelling: The swelling progresses through childhood and adolescence, often reaching its peak around puberty.
• Regression in Adulthood: In many cases, Cherubism is self-limiting. The lesions tend to stabilize or even regress spontaneously after puberty, often in the late 20s or early 30s. Bone may partially or fully remodel back to a more normal structure over time. However, the extent of regression is variable, and in some individuals, residual changes may persist into adulthood.

4. Skeletal Dysplasia (Specifically Craniofacial):

• Affects Bone Development: Cherubism is considered a type of skeletal dysplasia, which is a broad category of disorders affecting bone growth and development. In Cherubism, the primary focus is the craniofacial region, specifically the jaws.

Key Characteristics Summarized:

• Primary Location: Jaws (mandible and maxilla).
• Main Symptom: Painless, symmetrical swelling of the cheeks and jaws.
• Appearance: "Cherubic" face, rounded cheeks, often with the appearance of eyes turned upwards (due to cheek swelling pushing up the lower eyelids).
• Underlying Cause: Genetic mutation affecting bone development and remodeling.
• Benign Nature: Non-cancerous condition.
• Age-Related Course: Progressive in childhood, often regressing in adulthood.
• Other Potential Issues: Dental problems (malocclusion, delayed tooth eruption, missing teeth), speech difficulties, breathing problems in severe cases.

In simpler terms, Cherubism is a genetic condition that causes the jawbones to swell up, making children look like cherubs in paintings. While it’s not cancerous and often gets better as they get older, it can affect their appearance, teeth, and sometimes breathing or speech during childhood.

Is biopsy needed for diagnosis?

While a biopsy is not always absolutely necessary for the diagnosis of Cherubism, it is often recommended and considered a very valuable tool, especially in certain situations.

Here’s a breakdown of why and when a biopsy might be needed or not needed:

Situations where a biopsy is often recommended and helpful for diagnosis:

• Atypical Presentation: If the clinical presentation is not classic Cherubism. For example:

  • Unilateral or asymmetrical swelling: Cherubism is typically bilateral and symmetrical. If the swelling is only on one side or very uneven, other conditions need to be considered.
  • Unusual age of onset: While usually appearing in early childhood, atypical cases can present later.
  • Rapid progression: While Cherubism progresses, very rapid or painful growth might suggest other lesions.
  • Lack of family history: While autosomal dominant inheritance is common, spontaneous mutations occur. Without family history, ruling out other conditions becomes more important.

• Differential Diagnosis: Cherubism can sometimes resemble other fibro-osseous lesions of the jaws, such as:

  • Fibrous Dysplasia: This is a more common condition and can also cause jaw swelling. Biopsy helps differentiate them based on microscopic features.
  • Giant Cell Granuloma: These lesions can also be cystic and expansive in the jaws.
  • Ameloblastoma: A benign but locally aggressive tumor of the jaw, which needs to be ruled out.
  • Cysts: Various types of cysts in the jaw can mimic Cherubism.

  A biopsy allows for histopathological examination, which is crucial to differentiate Cherubism from these other conditions. The microscopic features of Cherubism are quite characteristic and can help confirm the diagnosis and exclude other possibilities.

• Unclear Imaging: While radiographic findings (X-rays, CT scans) are highly suggestive in Cherubism (multilocular cystic lesions in the jaws), sometimes the imaging may not be completely definitive. A biopsy can provide tissue confirmation.

• Research and Detailed Characterization: In research settings or for complex cases, a biopsy might be performed to further characterize the tissue and understand the disease process at a cellular level.

Situations where a biopsy might be less critical or even deferred initially:

• Classic Clinical Presentation: In a young child (2-5 years old) with:

  • Bilateral, symmetrical, painless swelling of the jaws.
  • "Cherubic" appearance.
  • Characteristic radiographic findings (multilocular cystic lesions on X-rays/CT scans).
  • Positive family history of Cherubism.

  In such cases, especially with strong clinical and radiographic evidence, and a known family history, a diagnosis of Cherubism can be made clinically and radiographically, and a biopsy might be deferred initially. However, even in these "classic" cases, many clinicians still prefer a biopsy to definitively confirm the diagnosis and rule out other conditions, especially before considering any surgical interventions.

• Genetic Confirmation: If genetic testing confirms the SH3BP2 gene mutation, this strongly supports the diagnosis of Cherubism. In some cases, genetic confirmation might reduce the perceived need for a biopsy, but it’s still often recommended for definitive histopathological confirmation and to exclude other possibilities.

In summary:

• Biopsy is not always mandatory for diagnosing Cherubism, especially in classic cases with strong clinical, radiographic, and family history evidence.
• However, a biopsy is highly recommended and considered a valuable diagnostic tool in most cases.
• It is particularly important when:
  • The presentation is atypical.
  • Differential diagnosis is necessary to rule out other conditions.
  • Imaging findings are not completely clear.
  • Definitive histopathological confirmation is desired before treatment decisions.

Ultimately, the decision to perform a biopsy is made on a case-by-case basis by the medical team (usually oral and maxillofacial surgeons, geneticists, and radiologists) considering all clinical, radiographic, genetic, and family history information.

1. Yamaguchi T, Dorfman HD, Eisig S. Cherubism: clinicopathologic features. Skeletal Radiol. 1999 Jun;28(6):350-3. doi: 10.1007/s002560050530. PMID: 10450884. ↩