Ellen Denayer, Eric Legius
DOI: 10.2340/00015555-3429

Neurofibromatosis type 1 (NF1) is the most common disorder characterized by multiple café-au-lait macules. Most individuals with this autosomal dominant disorder also have other features, such as skinfold freckling, iris Lisch nodules and benign or malignant peripheral nerve sheath tumours. Legius syndrome is a less frequent autosomal dominant disorder with similar multiple café-au-lait macules and skinfold freckling. Legius syndrome is not characterized by an increased risk of tumours, and a correct diagnosis is important. In young children with a sporadic form of multiple café-au-lait macules with or without freckling and no other manifestations of NF1 these 2 conditions cannot be differentiated based on clinical examination. Molecular analysis of the NF1 and SPRED1 genes is usually needed to differentiate the 2 conditions. Other less frequent conditions with café-au-lait macules are Noonan syndrome with multiple lentigines, constitutional mismatch repair deficiency and McCune-Albright syndrome.

Neurofibromatosis type 1 and Legius syndrome are both autosomal hereditary conditions with the same type of hyperpigmentation macules and skinfold freckles. Patients with neurofibromatosis type 1 usually develop additional signs, such as tumours of the peripheral nerves, and iris Lisch nodules. At a young age these additional signs might not be present, and the correct diagnosis can only be made by genetic testing, because these 2 conditions are caused by mutations in different genes. A correct diagnosis is essential because the medical follow-up is different.