Legius syndrome

  • Has the pigmentary lesions of NF1 but lacks tumoral growths
  • Etiology
    • loss-of-function mutation in SPRED1, which normally inhibits MAPK signalling
    • Inheritance: AD
    • May be mosaic
  • Mutation on SPRED1
    • Many patients have “NF1” diagnosis for many years, but changed due to genetic testing
  • Clinical presentation
    • Café au lait macules (>99% persons)
    • Skin freckling (30-50%), age dependent
    • Macrocephaly (20%)
    • Short stature (12%)
    • Neurobehavioral/developmental issues (30%)
    • Multiple lipomas (18%), in adults
    • Pectus deformity (12%)
    • Noonan-like facial features (15%)