Café-au-lait Macules and Neurofibromatosis Type 1: A Review of the Literature

Background: The first sign of neurofibromatosis type 1 (NF1) in a child is often the presence of multiple café-au-lait macules. Although previous studies reported that almost individuals with multiple café-au-lait macules will eventually develop NF1 based on clinical criteria, recent studies and clinical observations suggest that a significant percentage of them do not have NF1.

Methods: We conducted the first systematic review of the literature on the prevalence of definitive NF1 among patients referred for isolated café-au-lait macules, searching more precisely for the proportion of those patients who do not have NF1. Because we now know that the presence of café-au-lait macules and freckling might not distinguish between NF1 and other conditions such as Legius syndrome, definitive NF1 was defined as the presence of café-au-lait macules with or without freckling plus one of the following: Lisch nodules, neurofibroma, plexiform neurofibroma, bone dysplasia, optic pathway glioma, or familial history of NF1.

Results: Six articles reported sufficient data to meet our inclusion criteria. Grouping all studies together, we found that 19.5% to 57.1% of all patients with isolated café-au-lait macules did not have a diagnosis of NF1 after follow-up or genetic testing.

Conclusion: A significant portion of the patients presenting with isolated café-au-lait macules at initial consultation might not have NF1. Genetic testing could help guide the follow-up of those patients, but further evidence is required to make recommendations.