Molecular Genetic Confirmation of Jaffe-Campanacci Syndrome: A Case Report of the Third Identified Pathogenic NF1...

Jaffe-Campanacci syndrome (JCS) is a rare phenotypic variant of neurofibromatosis type 1 (NF1), characterized by café-au-lait macules (CALMs), multiple non-ossifying fibromas (NOFs), and occasionally central giant cell granulomas (CGCG) of the jaw. Although fewer than 30 cases have been reported to date, molecular genetic confirmation remains limited. This report presents the third known case of a confirmed pathogenic NF1 variant.

A 13-year-old boy with a history of multiple CALMs, axillary and inguinal freckling, Lisch nodules, and multiple NOFs in the lower extremities was diagnosed with JCS. Genetic testing revealed a pathogenic splice-site variant in NF1, confirming the molecular diagnosis. In addition, Sanger sequencing of DNA extracted from the affected cystic lesion tissue obtained during surgery identified the same variant, further supporting the diagnosis. Radiological findings, including lytic bone lesions in the lower extremities and brain MRI changes consistent with NF1, further supported this diagnosis. The patient also presented with a mild intellectual disability and attention-deficit/hyperactivity disorder.

This case highlights the clinical challenges and diagnostic complexity of JCS, which is a rare subtype of NF1. The patient's molecular confirmation adds to the growing body of evidence, supporting genetic testing of rare NF1 variants. The absence of CGCGs in this case underscores the broad phenotypic spectrum of JCS. A comprehensive evaluation, including molecular testing, is critical for accurate diagnosis and management.

This case reinforces the importance of considering rare NF1 subtypes, such as JCS, in patients presenting with multiple NOFs and typical skin findings. Early genetic confirmation is invaluable for guiding diagnosis and management, emphasizing the need for a multidisciplinary approach in rare genetic syndromes.