Legius Syndrome and Inflammatory Bowel Disease: A Pediatric Case Report

Legius syndrome (LS) is a rare and underrecognized disorder that is often misdiagnosed as neurofibromatosis type 1 (NF1). It is characterized by café-au-lait macules without the tumoral manifestations of NF1. We report the case of an 11-year-old patient with multiple café-au-lait macules and intertriginous freckling who was admitted for bloody stools, joint pain, and weight loss. His clinical and endoscopic findings were consistent with inflammatory bowel disease (IBD). He also met the clinical diagnostic criteria for NF1 but not for LS. Genetic testing played a pivotal role in the differential diagnosis and revealed a loss-of-function mutation in the SPRED1 gene, confirming the diagnosis of LS. This is the first reported case of a patient with IBD and LS. The subtle manifestations of LS make it an underdiagnosed disease, which reduces the likelihood of it being diagnosed in association with other diseases, such as IBD. There are, however, 10 published case reports linking IBD and NF1, and some pathophysiological mechanisms have been proposed. Continued reporting will help clarify the relationship between IBD and RASopathies such as NF1 and LS.