| Legius syndrome | |
| Synonyms: | Neurofibromatosis 1-like syndrome |
| Symptoms: | café au lait spots
|
| Onset: | at birth |
| Causes: | Mutations in the SPRED1 gene |
| Diagnosis: | Clinical findings, Genetic test |
| Differential: | neurofibromatosis type I |
| Treatment: | Physical therapy, Speech therapy |
| Prognosis: | good |
| Frequency: | rare (estimated at 1:46,000-1:75,000) |
Legius syndrome (LS) is an autosomal dominant condition characterized by cafe au lait spots.[1] It was first described in 2007 and is often mistaken for neurofibromatosis type I. It is caused by mutations in the SPRED1 gene.[2] [3] It is also known as neurofibromatosis type 1-like syndrome.
See also: List of conditions associated with café au lait macules. Nearly all individuals with Legius syndrome show multiple café au lait spots on their skin.[4] Symptoms may include:
Features common in neurofibromatosis – like Lisch nodules (iris hamartomas diagnosed on slit lamp exam), bone abnormalities, neurofibromas, optic pathway gliomas and malignant peripheral nerve sheath tumors – are absent in Legius syndrome.[5]
Legius syndrome is a phakomatosis[6] and a RASopathy, a developmental syndrome due to germline mutations in genes.[4] [7] The condition is autosomal dominant in regards to inheritance and caused by mutations to the SPRED1 gene at chromosome 15, specifically 15q14 (or (GRCh38): 15:38,252,086-38,357,248).[8] [9] The gene in question demonstrates almost 100 mutations.[5]
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.[10]
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.[11] [5] [12]
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.[13]
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.
Management of Legius syndrome is done via the following:[13] [5]
The prognosis of this condition is generally considered good with appropriate treatment.