Trait Document

Legius syndrome is a genetic condition characterized by multiple café-au-lait (i.e., coffee-colored) spots. Freckling typically found in the armpit and/or the groin areas, and varying degrees of macrocephaly (i.e., large head size) are also commonly seen in this condition. Lipomas (i.e. noncancerous fatty tumors) have been reported in some individuals with this condition. Learning disabilities, speech problems, and behavioral problems such as attention deficit hyperactivity disorder, are often seen in individuals with Legius syndrome.

Individuals with Legius syndrome may have a change or mutation in the SPRED1 gene that encodes the Spred-1 protein. This protein is involved in a complex signaling pathway called the “RAS-MAPK pathway” which is important for the proper formation of many different types of tissue during human development. A mutation in this gene disrupts this signaling pathway.

Management of Legius syndrome often involves developmental evaluations and educational interventions, especially if learning disabilities and/or behavioral problems are present. Some healthcare providers also recommend that individuals with Legius syndrome have routine blood pressure monitoring.

Legius syndrome is inherited in an autosomal dominant pattern. This means inheriting one SPRED1 mutation is enough for an individual to be affected and show signs of Legius syndrome. The mutation can be inherited from an affected parent or it can occur brand new (de novo) in an affected child.

The risk to family members depends on whether or not the individual with Legius syndrome has a parent affected with Legius syndrome. If a parent also has Legius syndrome, the risk of having a child with Legius syndrome is 50% with each pregnancy. If a parent does not have Legius syndrome, the risk of future pregnancies being affected is very low.

The features seen in Legius syndrome may resemble another genetic condition called Neurofibromatosis type 1 (NF1; see trait profile). While multiple café-au-lait spots, axillary and inguinal freckling are features common to both conditions, NF1 has additional features that are typically absent in Legius syndrome, such as Lisch nodules (i.e., dark pigmentation found within the iris of the eye that does not affect vision), cutaneous neurofibromas (i.e., noncancerous growths or tumors that appear on the skin, usually first appearing on the chest, stomach, and back), optic pathway gliomas (i.e., a type of brain tumor that arises around the optic nerve – the nerve that connects the eye to brain), and scoliosis. Since it can be difficult to distinguish these two conditions based on clinical features, results from genetic testing are often used to aid in making a diagnosis.