Lisch nodules and iris mammillations in two siblings with familial legius syndrome

Abstract

Legius syndrome is a recently described genetic syndrome that is characterized by multiple café-au-lait macules (CALMs) and can also include intertriginous freckling, lipomas, macrocephaly, and neurobehavioral disorders. Legius syndrome is caused by a mutation in the SPRED1 gene on chromosome 15 and is inherited in an autosomal dominant fashion. It is a rare disorder; the overall prevalence is unknown at this time, and most medical knowledge is based off of roughly 200 individuals with a genetically confirmed diagnosis. 1,2 Legius syndrome is also known as neurofibromatosis type 1-like syndrome, as the initial clinical presentation of Legius syndrome can be clinically indistinguishable from neurofibromatosis type 1 (NF1). However, the lifetime clinical courses and prognoses for these diseases are very different. NF1 is characterized by development of multiple types of benign growths later in life, including neurofibromas and Lisch nodules; therefore, Legius syndrome is usually clinically differentiated from NF1 by the absence of these tumors. 1,2 We report on a familial case of three patients with molecularly confirmed Legius syndrome, in which two female

Evaluation of the impact of the 2021 revised Neurofibromatosis type 1 diagnostic criteria on time to diagnosis

“…An additional complication in the diagnosis of NF1 is that the pigmentary findings, such as CALMs and skinfold freckling, are also seen in another RASopathy due to pathogenic variants in SPRED1 (i.e., Legius syndrome). The initial clinical presentation of Legius syndrome and NF1 can be clinically indistinguishable which can lead to the misdiagnosis of NF1 when strictly following the NIH diagnostic criteria (Bixel et al, 2020).…”