Legius syndrome
Medical condition
From Wikipedia, the free encyclopedia
Legius syndrome (LS) is an autosomal dominant condition characterized by cafe au lait spots.[3] It was first described in 2007 and is often mistaken for neurofibromatosis type I. It is caused by mutations in the SPRED1 gene.[5][6] It is also known as neurofibromatosis type 1-like syndrome.[1]
| Legius syndrome | |
|---|---|
| Other names | Neurofibromatosis 1-like syndrome[1] |
| |
| This condition is inherited in an autosomal dominant manner. | |
| Symptoms | café au lait spots; +/- learning disabilities[2] |
| Usual onset | at birth |
| Causes | Mutations in the SPRED1 gene[3] |
| Diagnostic method | Clinical findings, Genetic test[4] |
| Differential diagnosis | neurofibromatosis type I |
| Treatment | Physical therapy, Speech therapy[2][1] |
| Prognosis | good |
| Frequency | rare (estimated at 1:46,000-1:75,000)[2] |
Symptoms and signs
Nearly all individuals with Legius syndrome show multiple café au lait spots on their skin.[7] Symptoms may include:[2]
- 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 (iris hamartomas diagnosed on slit lamp exam), bone abnormalities, neurofibromas, optic pathway gliomas and malignant peripheral nerve sheath tumors – are absent in Legius syndrome.[1]
Cause
Legius syndrome is a phakomatosis[8] and a RASopathy, a developmental syndrome due to germline mutations in genes.[7][9] 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).[10][11] The gene in question demonstrates almost 100 mutations.[1]
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.[2][12]
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.[4][1][13]
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.[2]
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.[medical citation needed]
Treatment
Management of Legius syndrome is done via the following:[2][1]
- Physical therapy
- Speech therapy
- Pharmacologic therapy (e.g. methylphenidate for attention deficit hyperactivity disorder)[14]
The prognosis of this condition is generally considered good with appropriate treatment.[citation needed]
