Legius syndrome presents as a mild neurofibromatosis type 1 (NF1) phenotype. Multiple café-au-lait spots and macrocephaly are present with or without axillary or inguinal freckling. [repub.eur.nl]

In addition, macrocephaly, learning difficulties, and developmental delay may be present. [medicover-genetics.com]

Clinical description The clinical presentation of Legius syndrome is very similar to that of NF1. [orpha.net]

The present review aims to provide an overview of these 'NF1‑like' inherited diseases and recommend a cost‑effective strategy for making a clear diagnosis among these diseases with an ambiguous borderline. [ncbi.nlm.nih.gov]

Herein, we describe a case of a 16-year-old male presenting with multiple CALMs and axillary freckling. A 16-year-old male presented to us with multiple hyperpigmented lesions predominantly on the left side of chest and back for the last 2 years. [journals.lww.com]

• Disability

  Other features include axillary freckling, macrocephaly, Noonan-like facies, lipomas, learning disabilities and attention deficit-hyperactivity. [medical-dictionary.thefreedictionary.com]

  Constitutional heterozygous loss-of-function mutations in the SPRED1 gene cause a phenotype known as Legius syndrome, which consists of symptoms of multiple café-au-lait macules, axillary freckling, learning disabilities, and macrocephaly. [ncbi.nlm.nih.gov]

  Learning disabilities, speech problems, and behavioral problems such as attention deficit hyperactivity disorder, are often seen in individuals with Legius syndrome. [my46.org]

  Disability Strategy for 2010-20. [wikivisually.com]

• Pulmonary Valve Stenosis

  valve stenosis, arrhythmias and aortic dilatation). [admerahealth.com]

  valve stenosis, branch pulmonary arch stenosis and hypertrophic cardiomyopathy; undescended testes in boys; and skin and hair changes including cafe-au-lait macules (more common in NF1 and Legius syndrome), lentigines (most frequently with Leopard syndrome [genomicseducation.hee.nhs.uk]

  Approximately 85% of affected individuals have heart defects, including hypertrophic cardiomyopathy (HCM) (typically appearing during infancy and sometimes progressive) and pulmonary valve stenosis. [rasopathiesnet.org]

  The NS features include facial anomalies such as hypertelorism, low-set ears, short stature, congenital heart defects, primary pulmonary valve stenosis, webbed neck and thoracic abnormalities. [preventiongenetics.com]

  Severe narrowing of the pulmonary artery owing to a defective pulmonary valve (pulmonary valve stenosis) may require immediate intervention, either using balloon dilation or surgery. [socialstyrelsen.se]

• Pathologist

  Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing [invitae.com]

  The standards and guidelines developed by the American College of Medical Genetics and Genomics (ACMG), the Association for Molecular Pathology (AMP), and the College of American Pathologists (CAP) have now been implemented widely in laboratories offering [gimjournal.org]

• Pneumonia

  Legg-Calve-Perthes disease leggings Legg-Perthes disease Legg's disease -legia legibility Legionella Legionella bozemanii Legionella dumoffii Legionella feeleii Legionella gormanii Legionella longbeachae Legionella micdadei Legionella pneumonia Legionella [medical-dictionary.thefreedictionary.com]

  Similar skin features were present in the father, a healthy man with a medical history of recurrent pneumonia and constipation during childhood. During childhood he had failed to thrive and had short stature. [jmg.bmj.com]

• Freckles

  SCIENTIFIC BACKGROUND Description Legius syndrome, historically known as Neurofibromatosis type 1-like syndrome (NFLS), is characterized by multiple café-au-lait spots with or without additional freckle-like spots in the axilla or groin. [medicover-genetics.com]

  Individuals frequently fulfill the NIH diagnostic criteria for NF1 based on pigmentary manifestations of café-au-lait spots and distinctive freckling patterns. [arup.utah.edu]

  It is characterized mainly by café au lait macules, axillary freckling, and macrocephaly. Dr. [medscape.com]

  This supports the theory that mutation in the intracellular tyrosine kinase domain of KIT results in severe piebaldism and may be related to the appearance of CALMs and freckling. [dovepress.com]

• Cafe-Au-Lait Spots

  CASE REPORT: We present a 10 months child, without a personal interest history, consulting by hypotonic extremities, cafe-au-lait spots and mild psychomotor difficult. Mother's sister and grandfather have some cafe-au-lait spots. [ncbi.nlm.nih.gov]

  On assessment he was noted to have multiple cafe-au-lait spots >5 mm in diameter. Cafe-au-lait spots were also noted on his mother and brother. The rest of his clinical examination was unremarkable. [omicsonline.org]

  Keywords: Adolescent, Adult, Aged, Brain, Cafe-au-Lait Spots, Child, Child, Preschool, Female, HEK293 Cells, Humans, Infant, Intracellular Signaling Peptides and Proteins, Magnetic Resonance Imaging, Male, Membrane Proteins, Middle Aged, Mutation, Noonan [openaccess.sgul.ac.uk]

• Axillary Freckling

  Consider the possibility of Legius syndrome, which can be confirmed by molecular genetic analysis, in patients with six or more café au lait macules and axillary freckling but none of the other classic features of NF1, urged Dr. [mdedge.com]

  NF6 was ruled out by the presence of axillary freckling. NF-6 is characterized by only multiple CALMs. [journals.lww.com]

  Furthermore, axillary freckling was present on the left side [Figure 2]. Other features of NF were analyzed. Lisch nodules in iris and neurofibroma were absent. Lisch nodules were examined on slit-lamp examination. [go.gale.com]

• Macula

  Often CMMRD patient show skin patches of milk coffee-like color, termed café au lait maculae (CALM), which are very typical for a different inherited condition named neurofibromatosis type 1 (NF1). [clinicaltrials.gov]

  Maculae conditions misdiagnosed with CAL LEOPARD Syndrome Multiple lentigines, hypertelorism, sensorineural deafness, hypertrophic cardiomyopathy; autosomal dominant. [scielo.br]

• Flushing

  […] nerve, either within the orbit (eye socket) or at the topic chasm in front of the brain Pheochromocytoma – tumor of the adrenal gland that occurs rarely in adults with NF1; presents with high blood pressure, heart racing, palpitations, and episodes of flushing [childneurologyfoundation.org]

• Low-Set Posteriorly Rotated Ears

  Neonatal period: feeding difficulties and poor weight gain; distinctive craniofacial appearance, including hypertelorism, down slanted palpebral fissures, low-set posteriorly rotated ears, short neck with excess skin folds, low posterior hairline, coarseness [genomicseducation.hee.nhs.uk]

• Short Neck

  Neonatal period: feeding difficulties and poor weight gain; distinctive craniofacial appearance, including hypertelorism, down slanted palpebral fissures, low-set posteriorly rotated ears, short neck with excess skin folds, low posterior hairline, coarseness [genomicseducation.hee.nhs.uk]

  Other features shared between the two conditions include short stature, intellectual disability, lax joints, and head/neck features such as a highly arched palate, a short neck, a large forehead, and low-set ears. [forgottendiseases.org]

  Noonan syndrome : short size (40%-50%), facial dysmorphism (hypertelorism, antimongoloid palpebral fissures, ptosis, low-set and posteriorly rotated ears, etc.), short neck, cardiac abnormalities [50%-80%, pulmonary valve stenosis (20%-50%), hypertrophic [admerahealth.com]

  neck + + + + + +Pectus deformity + + + + + + + + +Cryptorchidism NA NA NA NA NA + +Skin changesKeratosis + + + + +Nevi/lentigines + + + + Caf-au-lait spots + Short stature2 SD + + + + + + + +>2 SD 1 SD + >1 SD Croonen et al. [docslide.com.br]

  Early recognition of the syndrome based on classical association of dysmorphic face, heart defect, short/ webbed neck, pectus and short stature is essential for starting GH therapy and for appropriate genetic counseling. [healthdocbox.com]

This delay can present a diagnostic challenge; it is often a difficult decision whether or not to pursue further workup for entities such as optic gliomas. [escholarship.org]

However, the molecular genetic workup can be performed in two steps: MLPA, followed by sequencing of the coding regions and splice sites (Grimm et al 2012). [healthdocbox.com]

Management and treatment Drug therapy should be considered for the behavioral manifestations of the disorder (ADHD). [orpha.net]

There are two main types of clinical studies: Clinical trials determine if a new test or treatment for a disease is effective and safe by comparing groups receiving different tests/treatments. [rarediseases.info.nih.gov]

[…] good with appropriate treatment. [en.wikipedia.org]

Prognosis Given the current knowledge of disease manifestations and complications, the prognosis for patients with Legius syndrome is considered to be very good. The documents contained in this web site are presented for information purposes only. [orpha.net]

Prognosis Given the current knowledge of disease manifestations and complications, the prognosis for patients with Legius syndrome is considered to be very good. Last updated: 7/1/2014 [rarediseases.info.nih.gov]

Etiology Legius syndrome is caused by heterozygous inactivating mutations in the SPRED1 gene (15q14), involved in regulation of the RAS-MAPK signal transduction pathway. Nearly 100 different mutations in this gene have been identified. [orpha.net]

His group contributed successfully towards the understanding of the molecular etiology of a number of tumours in NF1. [biocity.turku.fi]

Etiology Legius syndrome is caused by heterozygous inactivating mutations in the SPRED1gene (15q14), involved in regulation of the RAS-MAPK signal transduction pathway. Nearly 100 different mutations in this gene have been identified. [rarediseases.info.nih.gov]

Summary Epidemiology The prevalence of Legius syndrome is not known. Fewer than 200 cases have been reported to date. Prevalence may be higher than expected due to misdiagnosis of cases as neurofibromatosis type 1 (NF1, see this term). [orpha.net]

Epidemiology. The prevalence of Legius syndrome is not known. Romanisio G, Chelleri C, Scala M, Piccolo G, Carlini B, Gatti L, Capra V, Zara F, Bersano A, Pavanello M, De Marco P, Diana MC. [operativeneurosurgery.com]

Epidemiology The prevalence of Legius syndrome is not known. Fewer than 200 cases have been reported to date. Prevalence may be higher than expected due to misdiagnosis of cases as neurofibromatosis type 1 (NF1, see this term). [rarediseases.info.nih.gov]

Department of Pathophysiology and Transplantation, Pediatric Highly Intensive Care Unit, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. [unboundmedicine.com]

This novel mechanism for the regulation of neurofibromin provides a molecular bridge for understanding the overlapping pathophysiology of NF1 and Legius syndrome. [ncbi.nlm.nih.gov]

Impairments are discussed to be one of the underlying pathophysiological mechanisms of developmental disorders. [thieme-connect.com]

Retrieved. ^ "Hermansky-Pudlak Syndrome: Background, Pathophysiology, Epidemiology". 2017-06-13. ^ "Hermansky-Pudlak Syndrome". Hermansky-Pudlak Syndrome. University of Washington, Seattle. 1993. [popflock.com]

Phacoemulsification may help prevent intraoperative and postoperative bleeding in patients with the syndrome. [popflock.com]

Genetics and genomics About medical genetics Chromosome abnormalities Genetic services: when, where, how Identification, treatment and prevention of birth defects Multifactorial inheritance Neurofibromatosis and related disorders Non Traditional Inheritance [childrenswi.org]

A dental examination should be performed early, and extensive preventive dental care is important. [socialstyrelsen.se]

[…] of Secondary Complications Age-appropriate developmental assessment and neuropsychiatric evaluations could potentially result in the initiation of therapies to prevent developmental and behavioral complications. [ncbi.nlm.nih.gov]

PREVENTION There is no way to prevent the disorder other than to offer prenatal diagnostic testing to those at 50% risk of passing NF1 to a child. [childneurologyfoundation.org]