Pigmentary Findings in Neurofibromatosis Type 1–like Syndrome (Legius Syndrome):  Potential Diagnostic Dilemmas

The study by Messiaen and colleagues¹ in this issue of JAMA provides a significant advance in understanding the clinical presentation and genetic spectrum of individuals with SPRED1 mutations that alter sprouty-related EVH1 domain–containing protein 1 function. It is clearly a vanguard report for understanding neurofibromatosis type 1 (NF1)–like syndrome, recently designated Legius syndrome.² Legius syndrome is deemed a more appropriate term to avoid confusion in counseling families regarding anticipatory guidance. The term NF1-like syndrome implies overlap with myriad medical complications associated with NF1, which this report demonstrates is not the case. The few reports of individuals with loss-of-function SPRED1 mutations have shown that the primary phenotype of Legius syndrome is café au lait macules, sometimes associated with axillary freckling, inguinal freckling, or both.^3- 5 Messiaen et al¹ provide supportive information on the phenotype of Legius syndrome with an increased number of individuals, document the lack of a specific genotype-phenotype correlation, and clarify the clinical overlap with NF1.