Abstract
Legius syndrome (LS), caused by mutations in SPRED1, is a recently identified condition characterized primarily by multiple café-au-lait macules and skin fold freckling, findings that are also among the diagnostic criteria for Neurofibromatosis type 1 (NF1). Previously, many individuals presenting only with these cutaneous manifestations were diagnosed clinically with NF1 until molecular studies identified SPRED1 mutations in them. The aim of this study was to investigate the clinical experiences of genetic counselors with this newly identified patient population. We used an anonymous, online survey to collect information regarding health care providers’ experiences with LS, their discussions with patients describing the genetics and clinical impact of the condition, and perceived patient reactions to a change in diagnosis from NF1 to LS. A total of 175 individuals, primarily genetic counselors, responded, of whom 19 had seen a patient with a molecular diagnosis of the condition and 50 had discussed LS as a potential diagnosis. There was inter- and intra-clinic variability of clinical versus molecular methods of diagnosis, as well as clinical management after a SPRED1 mutation is identified. The majority of participants decrease patient management to annual physical exams after the change in diagnosis; however, some follow the patient as if he or she had NF1. Participants did not frequently discuss reproductive options or some of the rarer but serious reported manifestations of LS. Nearly half of participants did not provide patients with resources, likely because few currently exist. When transitioning diagnoses from clinical NF1 to molecular LS, participants reported that patients reacted primarily with relief at the comparatively milder phenotype, while the lack of longitudinal data caused frustration and anxiety in some. These findings suggest a lack of consistency in genetic counseling and clinical management of patients with Legius syndrome which may impact the care of this emerging patient population.