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. [ncbi.nlm.nih.gov]

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

Characteristic features are depigmented patches of skin and hair (as presented in Fig. 1 ). [doi.org]

• Mitral Valve Prolapse

  Examples of other findings reported in isolated or only a few individuals include fifth finger clinodactyly, Chiari I malformation, hypotonia, cataract, nephrolithiasis, urethral meatal stenosis, pulmonic stenosis and mitral valve prolapse, paroxysmal [ncbi.nlm.nih.gov]

  Fig 2.3.2: NS growth curve for case 2 (KRAS mutation); green arrow marks start of GH therapy (graph adapted from Hall, 2007) Diagnosed with heart defect at 6 Mo (atrial septal defect later closed; anterior mitral valve prolapse, mild mitral insufficiency [healthdocbox.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. [pediatricneurology.conferenceseries.com]

  Wikipedia : 74 Legius syndrome (LS) is an autosomal dominant condition characterized by cafe au lait spots. It was... more... [malacards.org]

• 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]

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

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

  Abstract Neurofibromatosis type 1 (NF1) is an hereditary disorder characterized by abnormal proliferation of multiple tissues of neural crest origin, and presents mainly with multiple café-au-lait macules, axillary freckling and neurofibromas. [ncbi.nlm.nih.gov]

• Hypopigmented Macule

  Other less common manifestations include short stature, macrocephaly, Noonan-like facies, pectus excavatum/carinatum, lipomas, hypopigmented macules, vascular lesions, learning disabilities, attention deficit/hyperactivity disorder (ADHD), and developmental [orpha.net]

• Xanthelasma

  […] individuals include fifth finger clinodactyly, Chiari I malformation, hypotonia, cataract, nephrolithiasis, urethral meatal stenosis, pulmonic stenosis and mitral valve prolapse, paroxysmal atrial tachycardia, tubular colonic adenoma, progressive dystonia, xanthelasmas [ncbi.nlm.nih.gov]

• Compulsive Disorder

  The patient had shown vocal and motor tics since the age of 7, without any changes in behavior or scholastic performance and without features of an associated obsessive-compulsive disorder or attention deficit hyperactivity disorder. [nature.com]

• Short Neck

  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]

  short neck, cardiac abnormalities [50%-80%, pulmonary valve stenosis (20%-50%), hypertrophic cardiomyopathy (HCM) (20%-30%) and other structural defects], developmental abnormalities, a variable degree of intellectual disability (25%), thoracic abnormalities [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]

  Ptosis and short neck, features frequently associated with 18p- [Turleau 2008], were attributed by Brenk et al. to the proximal half of 18p. These features were absent in our patient, in whom the proximal 5,1 Mb of 18p was not deleted. [healthdocbox.com]

• Language Delays

  Of the six individuals with developmental abnormalities described by Messiaen et al [2009], all had speech and/or language delays as the primary or only delay. [ncbi.nlm.nih.gov]

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]

• Nephrolithiasis

  Examples of other findings reported in isolated or only a few individuals include fifth finger clinodactyly, Chiari I malformation, hypotonia, cataract, nephrolithiasis, urethral meatal stenosis, pulmonic stenosis and mitral valve prolapse, paroxysmal [ncbi.nlm.nih.gov]

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

Please consult your own licensed physician regarding diagnosis and treatment of any medical condition! Please see also our disclaimer. This site complies with the HONcode standard for health information: verify here. Database updated 2019-02-19. [diseasesdatabase.com]

CLOSE Medical Disclaimer The medical information on this site is provided as an information resource only, and is not to be used or relied on for any diagnostic or treatment purposes. [resourcerepository.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]

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]

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]

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]

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]

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

Report of three cases and review of pathophysiology and management considerations". Medicine. 64 (3): 192-202. doi : 10.1097/00005792-198505000-00004. ISSN 0025-7974. PMID 3921802. Davies, Bh; Tuddenham, Eg (April 1976). [popflock.com]

[…] 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]

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

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

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]