Legius syndrome

Legius syndrome is an autosomal dominant condition characterized by cafe au lait spots. It was first described in 2007 and is often mistaken for neurofibromatosis type I. It is caused by mutations in the SPRED1 gene. It is also known as neurofibromatosis type 1-like syndrome.

Symptoms and signs

[Image:Cafe au lait fleck.jpg|thumb|right|larger café au lait spot on right forearm]
Nearly all individuals with Legius syndrome show multiple café au lait spots on their skin.
Symptoms may include:

Freckles in the axillary and inguinal skin fold
Lipomas, developing in adulthood
Macrocephaly
Learning disabilities
Attention deficit hyperactivity disorder
Developmental delay

Features common in neurofibromatosis – like Lisch nodules, bone abnormalities, neurofibromas, optic pathway gliomas and malignant peripheral nerve sheath tumors – are absent in Legius syndrome.

Cause

Legius syndrome is a phakomatosis and a RASopathy, a developmental syndrome due to germline mutations in genes. The condition is autosomal dominant in regards to inheritance and caused by mutations to the SPRED1 gene at chromosome 15, specifically 15q14. The gene in question demonstrates almost 100 mutations.

Mechanism

A mutated SPRED1 protein adversely regulates Ras-MAPK signaling, which is a chain of proteins in a cell that sends signals from the surface of a cell to the nucleus which in turn causes the symptoms of this condition.

Diagnosis

Genetic testing is necessary to identify the syndrome. The DNA test is necessary sometimes, because symptoms may not be sufficient to definitely diagnose this condition.

Differential diagnosis

The symptoms of Legius syndrome and neurofibromatosis type I are very similar; An important difference between Legius syndrome and neurofibromatosis type I is the absence of tumor growths Lisch nodules and neurofibromas which are common in neurofibromatosis type I.
A genetic test is often the only way to make sure a person has Legius syndrome and not neurofibromatosis type I; the similarity of symptoms stem from the fact that the different genes affected in the two syndromes code for proteins that carry out a similar task in the same reaction pathway.

Treatment

Management of Legius syndrome is done via the following:

Physical therapy
Speech therapy
Pharmacologic therapy

The prognosis of this condition is generally considered good with appropriate treatment.