Legius syndrome (LS) is an

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

condition characterized by cafe au lait spots."Legius syndrome"
Genetics Home Reference,

National Institutes of Health The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. It was founded in 1887 and is part of the United States Department of Health and Human Service ...

It was first described in 2007 and is often mistaken for

neurofibromatosis type I Neurofibromatosis type I (NF-1), or von Recklinghausen syndrome, is a complex multi-system neurocutaneous disorder caused by a subset of genetic mutations at the neurofibromin 1 (''NF1'') locus. Other conditions associated with mutation of the ...

. It is caused by mutations in the ''

SPRED1 Sprouty-related, EVH1 domain-containing protein 1 (pronounced ''spread-1'') is a protein that in humans is encoded by the ''SPRED1'' gene located on chromosome 15q13.2 and has seven coding exons. Function SPRED-1 is a member of the Sprouty fa ...

'' gene. It is also known as neurofibromatosis type 1-like syndrome.

Symptoms and signs

Nearly all individuals with Legius syndrome show multiple café au lait spots on their skin. Symptoms may include: *

Freckles Freckles are clusters of concentrated melaninized cells which are most easily visible on people with a fair complexion. Freckles do not have an increased number of the melanin-producing cells, or melanocytes, but instead have melanocytes that ...

in the axillary and inguinal skin fold *

Lipoma A lipoma is a benign tumor made of adipose tissue, fat tissue. They are generally soft to the touch, movable, and painless. They usually occur just under the skin, but occasionally may be deeper. Most are less than in size. Common locations inc ...

s, developing in adulthood *

Macrocephaly Macrocephaly is a condition in which circumference of the human head is abnormally large. It may be pathological or harmless, and can be a Heredity, familial genetic characteristic. People diagnosed with macrocephaly will receive further medical ...

Learning disabilities Learning disability, learning disorder, or learning difficulty (British English) is a condition in the brain that causes difficulties comprehending or processing information and can be caused by several different factors. Given the "difficulty ...

Attention deficit hyperactivity disorder Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by symptoms of inattention, hyperactivity, impulsivity, and emotional dysregulation that are excessive and pervasive, impairing in multiple con ...

Developmental delay The term developmental delay can refer to: *Global developmental delay, an umbrella term used when children are significantly delayed in two or more areas of development *Specific developmental disorder, a classification of disorders characterize ...

Features common in neurofibromatosis – like Lisch nodules (iris hamartomas diagnosed on slit lamp exam), bone abnormalities,

neurofibromas A neurofibroma is a benign nerve-sheath tumor in the peripheral nervous system. In 90% of cases, they are found as stand-alone tumors (solitary neurofibroma, solitary nerve sheath tumor or sporadic neurofibroma), while the remainder are found in ...

, optic pathway

gliomas A glioma is a type of primary tumor, primary Neoplasm, tumor that starts in the glial cells of the Human brain, brain or spinal cord. They are Malignancy, malignant but some are extremely slow to develop. Gliomas comprise about 30% of all brain ...

and malignant peripheral nerve sheath tumors – are absent in Legius syndrome.

Cause

Human male karyotpe high resolution - Chromosome 15 cropped

Legius syndrome is a phakomatosis and a RASopathy, a developmental syndrome due to germline mutations in genes. The condition is

in regards to inheritance and caused by mutations to the ''

'' gene at

chromosome 15 Chromosome 15 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 15 spans about 99.7 million base pairs (the building material of DNA) and represents between 3% and 3.5% of the total DNA ...

, specifically 15q14 (or (GRCh38): 15:38,252,086-38,357,248). 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 Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...

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

which are common in neurofibromatosis type I.update 2015 A

genetic test Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...

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 In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

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 Physical therapy (PT), also known as physiotherapy, is a healthcare profession, as well as the care provided by physical therapists who promote, maintain, or restore health through patient education, physical intervention, disease preventio ...

Speech therapy Speech is the use of the human voice as a medium for language. Spoken language combines vowel and consonant sounds to form units of meaning like words, which belong to a language's lexicon. There are many different intentional speech acts, suc ...

* Pharmacologic therapy (e.g.

methylphenidate Methylphenidate, sold under the brand names Ritalin ( ) and Concerta ( ) among others, is a central nervous system (CNS) stimulant used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It may be taken Oral adm ...

for attention deficit hyperactivity disorder) The prognosis of this condition is generally considered good with appropriate treatment.

References

External links

PubMed
{{Deficiencies of intracellular signaling peptides and proteins Genodermatoses Neuro-cardio-facial-cutaneous syndromes RASopathies