Distinguishing Familial Benign Café au Lait Macules from Legius Syndrome

Key Clinical Differences

The American College of Medical Genetics and Genomics notes that Legius syndrome is caused by germline loss-of-function mutations in the SPRED1 gene, distinguishing it from familial benign café au lait macules 2
The presence of multiple café au lait macules with or without intertriginous freckling is a characteristic of Legius syndrome, as reported by the National Institutes of Health 1, 2

The National Cancer Institute guidelines indicate that both familial benign café au lait macules and Legius syndrome lack increased tumor risk compared to the general population, specifically absent are neurofibromas, optic pathway gliomas, and NF1-associated bone abnormalities 1, 2
The American Academy of Pediatrics recommends that patients with Legius syndrome do not require cancer surveillance, as they do not have an increased risk of developing tumors 1, 2

The National Institutes of Health recommends documenting the precise phenotype of patients with multiple café au lait macules, including counting and measuring all CALMs, to differentiate between familial benign café au lait macules and Legius syndrome 3, 4

The American College of Medical Genetics and Genomics states that both familial benign café au lait macules and Legius syndrome follow autosomal dominant inheritance with a 50% offspring recurrence risk 3
The National Society of Genetic Counselors emphasizes the importance of distinguishing between familial benign café au lait macules and Legius syndrome, as the counseling differs dramatically, with reassurance about absence of tumor risk and normal life expectancy for familial CALMs, and counseling about potential learning disabilities and developmental delays for Legius syndrome 1, 2, 3