Significance of the Absence of Focal Areas of Signal Intensity on Brain Magnetic Resonance Imaging Examinations in Legius Syndrome.

Background: Legius syndrome (LGSS) is a rare neurocutaneous disorder that is differentiated from neurofibromatosis type I (NF1) based on pathogenic variants in the SPRED1 gene (15q14). Similar to NF1, LGSS also presents with café-au-lait macules on the skin and sometimes intertriginous freckling; however, the other diagnostic features of NF1 are absent in LGSS. Clinical contradistinction from NF1 is important for an LGSS diagnosis, but molecular genetic confirmation is necessary. Hypersignal areas on T2-weighted magnetic resonance imaging (MRI) (focal areas of signal intensity [FASI]) in specific brain locations are another common clinical finding in NF1. The aim of this study is to compare the incidence of FASI in LGSS and NF1 in an effort to further distinguish these two clinical entities and evaluate the clinical and diagnostic significance of an absence of FASI in LGSS.

Methods: We have examined a group of 16 children with LGSS and a group of 130 children with NF1. All children had been clinically and molecularly diagnosed with LGSS or NF1 and had had MRI examinations of their brains. FASI findings on these scans were evaluated. The independence of FASI on diagnosis was evaluated using the Fischer exact test.

Results: FASI were found in 116 of 130 (89%) children with NF1, and no FASI was detected in children with LGSS (zero of 16, 0%). The presence of FASI was significantly dependent on the diagnosis.

Conclusions: We suggest that the absence of FASI on brain MRI examinations of patients with LGSS is an important clinical and diagnostic feature of this disorder.