If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a pdf plugin installed and enabled in your browser. Klein1,2 1program in craniofacial and mesenchymal biology, and division of craniofacial anomalies, department of orofacial sciences. We described a first solitary case of legius syndrome identified by next. Enable javascript to view the expandcollapse boxes. It is a challenge to differentiate the two diseases. Legius syndrome genetic and rare diseases information. Genetic testing of spred1 is necessary to confirm the diagnosis of legius syndrome, a syndrome characterized by multiple pigmented skin lesions. Legius syndrome is an autosomal dominant condition characterized by multiple cafe aulait macules and axillary or inguinal freckling, without neurofibromas or other tumor symptoms of neurofibromatosis type 1 nf1. The documents contained in this web site are presented for information purposes only. Legius syndrome is inherited in an autosomal dominant fashion. A negative test does not rule out the possibility of nf1 or legius syndrome.
The spred1 variants repository for legius syndrome. Pdf legius syndrome in fourteen families yolande van. Prior to the discovery of the gene for legius syndrome in 2007, many individuals with these two benign skin findings were thought to. Each child of an individual with legius syndrome has a 50% chance of inheriting the pathogenic variant. Legius syndrome in fourteen families keio university. Genetic test for legius syndrome by ambry genetics ambry. Legius syndrome genetic and rare diseases information center. In 2007 we reported that some individuals with multiple calms have a heterozygous mutation in the spred1 gene and have nf1like syndrome, or legius syndrome. Legius syndrome nfls, neurofibromatosis type 1like syndrome. Her family history was remarkable for the presence of multiple cafeaulait spots in the mother, the grandfather and two aunts. It is also known as neurofibromatosis type 1like syndrome. Legius syndrome definition of legius syndrome by medical.
As a group, the rasopathies are one of the largest groups of malformation syndromes known, affecting 1. Rasopathiesnet genetic and rare diseases information center. Other typical nf1 associated features lisch nodules, bone abnormalities, neurofibromas, optic pathway gliomas are. Neurofibromatosis 1like syndrome, or legius syndrome, is an autosomal dominant disorder resembling neurofibromatosis 1 with cafeaulait spots, axillary freckling, macrocephaly, learning disabilities, adhd, developmental delays, and dysmorphic facial features similar to. Wed like to understand how you use our websites in order to improve them. It was first described in 2007 and is often mistaken for neurofibromatosis type i nf1. The mutation caused a sub stitution of a glutamic acid gag with a termi nator. Tests for a mutation previously identified in a family member. Almost all affected individuals have multiple cafeaulait spots, which are flat patches on the skin that are darker than the surrounding area. These mutations lead to a nonfunctional spred 1 protein, usually because the mutated gene provides instructions for a shortened. The test targets individuals with clinical signs compatible with noonan syndrome and other related syndromes such as cardiofaciocutaneous syndrome, costello syndrome, leopard syndrome, watson syndrome and legius syndrome. Nf1 legius neither unknown if yes, attach a pedigree or specify the relationship of the family memberss to the patient and detail the symptomsage of onset in each symptomatic relative. The spred1 variants repository for legius syndrome g3. There are only roughly 200 known cases of legius syndrome but our genetics doctor said shes sure there are way more living with this syndrome that dont know it.
It was first described in 2007 and is often mistaken for neurofibromatosis type i. Please fill out this form and submit it with the test request form or electronic packing list. Legius syndrome is an autosomal dominant disorder that shows some similarities to neurofibromatosis type i nf1. Includes noonan syndrome, cfc syndrome, costello syndrome 11 genes in pathway incidence 15000 births. When a parent has a spred1 mutation, each offspring has a 50% risk of inheriting the mutation. Apparently legius syndrome causes cals freckling and possible learning disabilities but no neurofibromas or lisch nodules of which i do not have. Legius syndrome ls is an autosomal dominant condition characterized by cafe au lait spots. Cooperative regulation of rasmapk pathway signaling by.
Legius syndrome, also known as nf1like syndrome, is a rare, genetic skin pigmentation disorder characterized by multiple cafeaulait macules with or without axillary or inguinal freckling. Another pigmentation change, freckles in the armpits and groin, may occur in some affected individuals. Spred1 lossoffunction mutations identified in legius syndrome patients were unable to regulate ras activity levels. Refer to the guidance for save use of personal mobile devices provided by british association of dermatologists, australian medical association andor new zealand medical association medical image management apps.
Individuals frequently fulfill the nih diagnostic criteria for nf1 based on pigmentary manifestations of. Legius syndrome, special nf1 cases table 4 and other diagnoses green lines are. An external file that holds a picture, illustration, etc. Individuals with legius syndrome typically have multiple cafeaulait spots, sometimes associated with skin fold freckling. Legius syndrome presents as an autosomal dominant condition characterized by cafeaulait macules with or without freckling and sometimes a noonanlike appearance andor learning difficulties. It is also known as neurofibromatosis type 1like syndrome nfls. Legius syndrome is characterized by the presence of multiple cafeaulait spots and axillary and inguinal freckling. Legius et al 1990, ostri et al 1991, chitayat et al 1992. Here we report a legius syndrome like patient who finally was identified as nf1 with a novel mutation in. Advances in the treatment of neurofibromatosisassociated tumours. Case a 8monthold female child was referred to our dermatologic unit for suspected neurofibromatosis type 1 nf 1, because of the appearance of several cafeaulait macules. The features seen in legius syndrome may resemble another genetic condition called neurofibromatosis type 1 nf1. Germline lossoffunction variants in spred1, a negative regulator of the rasmapk pathway, cause a neurofibromatosis type 1like phenotype, first described in 2007 legius syndrome. Individuals with legius syndrome typically have multiple cafeaulait spots, sometimes associated with skin fold freckling, variable dysmorphic features such as hypertelorism or.
Legius syndrome cal only, frequently familial, no nf1 mutation mccunealbright syndrome always mosaicism, osseous fibrous dysplasia, precocious puberty piebaldism white spots thorax and forehead genetic instability syndromes cmmrd childhood cancer, pilomatricomas, frequent consanguinity. Legius syndrome is an autosomal dominant disorder caused by heterozygous inactivating mutations in the spred1 gene. Table 1 characteristic findings in branchiootorenal syndrome ing loss in the other ear have been reported karmody, 1974. January 20 mutations in the spred1 gene have been found in patients with legius syndrome, originally termed neurofibromatosis type 1like syndrome. The disorder is quite similar to and may be misdiagnosed as neurofibromatosis type 1. Legius syndrome ls is an autosomal dominant disorder caused by germline lossoffunction mutations in the sproutyrelated, evh1 domain containing 1 spred1 gene. Legius syndrome ls is characterized by multiple cafe au lait macules without neurofibromas or other tumor manifestations of neurofibromatosis type 1 nf1. Legius syndrome ls, caused by mutations in spred1, is a recently identified condition characterized primarily by multiple cafeaulait macules and skin fold freckling, findings that are also among the diagnostic criteria for neurofibromatosis type 1 nf1. What links here related changes upload file special pages permanent link page information. Cafeaulait macules and intertriginous freckling in.
She is 8 years old and has cafe au lait spots, and freckling in the armpit and groin. Legius syndrome is found in some people who have mild nf1type symptoms, but have no mutation in the nf1 gene omim 61. Legius syndrome is caused by germline lossoffunction spred1 mutations, resulting in overactivation of the rasmapk signal transduction cascade. Additional clinical manifestations reported commonly include intertriginous freckling, lipomas, macrocephaly, and learning disabilities adhd developmental delays. Noonan syndrome with multiple lentigines formerly called leopard syndrome is a condition that affects many areas of the body. Hirecently my daughter was sent to a specialist to be evaluated for nf1 legius syndrome. Legius syndrome often mistaken for neurofibromatosis type 1. Investigating genetic counselors experiences with legius. It is characterised by multiple cafeaulait macules calm with or without axillary or inguinal freckling and mild macrocephaly. For language access assistance, contact the ncats public information officer. A genetic test for legius syndrome using next generation sequencing. Pdf legius syndrome in fourteen families hilde brems.
These syndromes include noonan syndrome ns, noonan syndrome with multiple lentigines nsml or leopard syndrome, neurofibromatosis type 1 nf1, costello syndrome cs, cardiofaciocutaneous cfc syndrome, neurofibromatosis type 1like syndrome nfls or legius syndrome and capillary malformationarteriovenous malformation syndrome cmavm. The otologic aspects of the external ear are often the most striking feature of bor syndrome. Abstractlegius syndrome ls is an autosomal dominant disorder caused by germline lossoffunction. Jul 01, 2014 legius syndrome is differentiated from nf1 by the absence of the nonpigmentary clinical manifestations seen in this disorder i. If you have problems viewing pdf files, download the latest version of adobe reader. Craniofacial and dental development in costello syndrome. The phenotype of ls is multiple cafe au lait macules calm with other commonly reported manifestations, including intertriginous freckling, lipomas, macrocephaly, and learning disabilities including adhd and developmental delays. Management of a child with legius syndrome includes therapies for developmental delays, learning disorders, and adhd.
Other features include axillary freckling, macrocephaly, noonanlike facies, lipomas, learning disabilities and attention deficithyperactivity. Legius syndrome, also known as nf1like syndrome, is a rare, genetic skin. Legius syndrome is caused by spred1 mutations on chromosome 15q. Legius syndrome, also known as nf1like syndrome, is a rare, genetic skin pigmentation disorder characterized by multiple. Correct diagnosis is essential because of the differences in prognosis and longterm monitoring between legius syndrome and nf1. This condition is caused by a mutation in a different gene, spred1 omim 609291, and while freckling or cafeaulait patches can be present, there are usually no tumours or neurofibromas, and less likelihood of severe. Another pigmentation change, freckles in the armpits and groin, may occur in some affected. Legius syndrome is a condition characterized by changes in skin coloring pigmentation. Craniofacial and dental development in costello syndrome alice f. Rasopathiesnet genetic and rare diseases information. Messiaen3 1department of pediatrics, university of tennessee college of medicine, chattanooga, tennessee 2casey eye institute molecular diagnostic laboratory, portland, oregon 3department of genetics, university of alabama, birmingham, alabama. What is legius syndrome definition legius syndrome is an autosomal dominant condition characterized by multiple cafeaulait macules and axillary or inguinal freckling, without neurofibromas or other tumor symptoms of neurofibromatosis type 1 nf1. Mutations in the spred1 gene have been found in patients with legius syndrome, originally termed neurofibromatosis type 1like syndrome. The invitae legius syndrome test analyzes spred1, a gene that is associated with legius syndrome.
People with legius syndrome have multiple calms, intertriginous freckling fig 3, learning disabilities, and relative macrocephaly that is indistinguishable from. Legius syndrome was first described in 2007 in a group of individuals who met the nih diagnostic criteria for nf1 but who had no identifiable mutation in the nf1 gene. The rasopathies are a genetically heterogeneous group of disorders caused by variants in the genes involved in the rasmapk pathway. Legius syndrome is differentiated from nf1 by the absence of the nonpigmentary clinical manifestations seen in this disorder i. A collection of disease information resources and questions answered by our genetic and rare diseases information specialists for legius syndrome.
The information below is required to perform neurofibromatosis type i legius syndrome testing. Legius syndrome nfls, neurofibromatosis type 1like. E198598 january 2011 with 500 reads how we measure reads. In japan, a family with legius syndrome was first described in 2015 by sakai et al. Dec 17, 2015 legius syndrome is quite new to some doctors so they may just clinically diagnose someone with nf1 because of the cafe au lait spots or axillary freckling. Legius syndrome is a genetically distinct but similar disorder. This pathway is involved in a signal transduction cascade that is necessary for the proper. The clinical course or severity of symptoms cannot be. Because of the presence of isolated calms in many family members, we hypothesized a legius syndrome, an autosomal dominant disease characterized by a mild nf 1 phenotype. Health supervision for children with neurofibromatosis type 1.
Lisch nodules, neurofibromas, optic glioma, bone abnormalities. Legius syndrome is one of the ras opathies, which are a class of pediatric disorders associated with genes that are members of the mitogenactivated protein kinase rasmapk pathway. Legius syndrome is an autosomal dominant condition characterized by cafe au lait spots. Owing to the many similarities with neurofibromatosis type 1 nf1, legius syndrome was initially identified as nf1like syndrome. She was born with these, but not until a recent pediatrician change were we aware that this could be a sign of nf1 or legius syndrome. Legius syndrome, which is caused by pathogenic variants in the spred1 gene, has marked similarity to nf1. Noonan syndrome with multiple lentigines genetics home. Goodwin,1 snehlata oberoi,1 maya landan,1 cyril charles,1 jessica c. Mar 01, 2011 hirecently my daughter was sent to a specialist to be evaluated for nf1 legius syndrome.
The condition is a rasopathy, a group of developmental syndromes due to germline mutations in genes. Nf1 like syndrome or legius syndrome neurofibromatosis. Nextgen rasopathy panel school of medicine genetics uab. Legius syndrome is a rare genetic disorder characterized by multiple cafe au lait macules and other clinical manifestations like freckling, lipomas, macrocephaly, learning disabilities, developmental delays. Legius syndrome, is a recently identified autosomal dominant disorder caused by loss of function mutations in the spred1 gene, with individuals mainly presenting with multiple cafeaulait. Similar to nf1, individuals with legius syndrome have multiple cafeaulait macules. Legius syndrome presents as an autosomal dominant condition characterized by cafeaulait macules with. As the condition name suggests, noonan syndrome with multiple lentigines is very similar to a condition called noonan syndrome, and it can be difficult to tell the two disorders apart in early childhood. If any one has more info id be super interested in it as i have a few weeks before i get my genetic testing done. Spred1 functions as a negative regulator of the rasmapk pathway, however, the underlying molecular mechanism is poorly understood. Legius syndrome is a rare genetic disorder caused by heterozygous germ line loss.
Legius syndrome in fourteen families article pdf available in human mutation 321. It is caused by germline lossoffunction spred1 mutations and is a member of the rasmapk pathway syndromes. We found spred1 functioned by reducing rasgtp levels. Individuals with legius syndrome have multiple calms with or without freckling, but they do not show the typical. Neurofibromatosis 1like syndrome, or legius syndrome, is an autosomal dominant disorder resembling neurofibromatosis 1 with cafeaulait spots, axillary freckling, macrocephaly, learning disabilities, adhd, developmental delays, and dysmorphic facial features similar to noonan syndrome denayer et al. Case report earlycutaneoussignsof neurofibromatosistype1.
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