Orbital nodular fasciitis in child with biallelic germline RBL2 variant

Area of Science:

• Genetics
• Developmental Biology
• Oncology

Background:

• RBL2/p130 is a key member of the retinoblastoma protein family, crucial for neuronal development and survival.
• RBL2 functions as a tumor suppressor gene, with loss-of-function variants linked to profound developmental delay.
• Dysregulation of RBL2 has been observed in various cancers.

Observation:

• A child with developmental delay, microcephaly, and hypotonia presented with an orbital mass.
• The orbital mass was diagnosed as nodular fasciitis, a mesenchymal tumor.
• Genetic analysis revealed a biallelic frameshift variant (c.901dupT) in the RBL2 gene.

Findings:

• The identified RBL2 variant represents a germline loss-of-function mutation.
• This case is the first to report an association between RBL2 variants and orbital tumors.
• Unlike previous reports, this case involves a tumor manifestation.

Implications:

• This case expands the known clinical spectrum associated with RBL2 variants.
• It suggests a potential role for RBL2 in the pathogenesis of mesenchymal tumors, specifically orbital ones.
• Further research is warranted to elucidate the mechanism linking RBL2 to orbital tumor development.