Legius syndrome

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]

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]

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]}

See also

• List of cutaneous conditions
• List of genes mutated in cutaneous conditions

References

Further reading

• MD, Robert P. Erickson; PhD, Anthony J. Wynshaw-Boris MD (2016). Epstein's Inborn Errors of Development: The Molecular Basis of Clinical Disorders of Morphogenesis. Oxford University Press. ISBN 9780190275426. Retrieved 1 June 2017.
• Zhang, Jia (2016). "Molecular screening strategies for NF1-like syndromes with café-au-lait macules". Molecular Medicine Reports. 14 (5): 4023–4029. doi:10.3892/mmr.2016.5760. PMC 5112360. PMID 27666661. Review

External links

• PubMed

Scholia has a topic profile for Legius syndrome.

This page was last edited on 15 April 2024, at 07:08