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    410 results match your criteria LEOPARD Syndrome

    1 OF 9

    Accelerated Cardiomyocyte Proliferation in the Heart of a Neonate With LEOPARD Syndrome-Associated Fatal Cardiomyopathy.
    Circ Heart Fail 2018 Apr;11(4):e004660
    Department of Pediatrics (Y.N., R.I., H.T., S.K., K.S., H.A., T.S., Y.H., A.O.), Department of Pathology (K.I., M.H.), Department of Cardiovascular Medicine (N.T.), and Department of Developmental Medical Sciences (M.S.), Graduate School of Medicine, The University of Tokyo, Japan.

    Gain-of-function mutations in the gene encoding the tyrosine phosphatase SHP2 induce hydrocephalus in a catalytically dependent manner.
    Sci Signal 2018 Mar 20;11(522). Epub 2018 Mar 20.
    Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322, USA.
    Catalytically activating mutations in , which encodes the protein tyrosine phosphatase SHP2, cause 50% of Noonan syndrome (NS) cases, whereas inactivating mutations in are responsible for nearly all cases of the similar, but distinct, developmental disorder Noonan syndrome with multiple lentigines (NSML; formerly called LEOPARD syndrome). However, both types of disease mutations are gain-of-function mutations because they cause SHP2 to constitutively adopt an open conformation. We found that the catalytic activity of SHP2 was required for the pathogenic effects of gain-of-function, disease-associated mutations on the development of hydrocephalus in the mouse. Read More

    Clinical Presentation and Natural History of Hypertrophic Cardiomyopathy in RASopathies.
    Heart Fail Clin 2018 Apr;14(2):225-235
    Pediatric Cardiology, Department of Pediatrics, Sapienza University, Viale Regina Elena 324, Rome 00161, Italy.
    RASopathies are a heterogeneous group of genetic syndromes characterized by mutations in genes that regulate cellular processes, including proliferation, differentiation, survival, migration, and metabolism. Excluding congenital heart defects, hypertrophic cardiomyopathy is the most frequent cardiovascular defect in patients affected by RASopathies. A worse outcome (in terms of surgical risk and/or mortality) has been described in a specific subset of Rasopathy patients with early onset, severe hypertrophic cardiomyopathy presenting with heart failure. Read More

    Patient with confirmed LEOPARD syndrome developing multiple melanoma.
    Dermatol Pract Concept 2018 Jan 31;8(1):59-62. Epub 2018 Jan 31.
    Department of Dermatology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.
    LEOPARD syndrome, also known as Gorlin syndrome II, cardiocutaneous syndrome, lentiginosis profusa syndrome, Moynahan syndrome, was more recently coined as Noonan syndrome with multiple lentigines (NSML), inside the RASopathies. Historically, the acronym LEOPARD refers to the presence of distinctive clinical features such as: lentigines (L), electrocardiographic/conduction abnormalities (E), ocular hypertelorism (O), pulmonary stenosis (P), genital abnormalities (A), retardation of growth (R), and sensorineural deafness (D). This condition is identified in 85% of patients with phenotype hallmarks caused by presence a germline point mutation in PTPN11 gene. Read More

    Activation of Autophagy Ameliorates Cardiomyopathy in -Targeted Knockin Mice.
    Circ Heart Fail 2017 Oct;10(10)
    From the Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Germany (S.R.S., A.T.L.Z., B.G., S.R.-D., M.P., E.K., S.S., L.C.); DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany (S.R.S., A.T.L.Z., B.G., S.R.-D., M.P., E.K., S.S., L.C.); Department of Pediatrics, The Heart Institute, The Cincinnati Children's Hospital Medical Center, OH (S.R.S., H.O., Q.M., J.R.); Radcliffe Department of Medicine, University of Oxford, United Kingdom (C.R.); Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (J.v.d.V.); and ICIN-Netherlands Heart Institute, Utrecht (J.v.d.V.).
    Background: Alterations in autophagy have been reported in hypertrophic cardiomyopathy (HCM) caused by Danon disease, Vici syndrome, or LEOPARD syndrome, but not in HCM caused by mutations in genes encoding sarcomeric proteins, which account for most of HCM cases. , encoding cMyBP-C (cardiac myosin-binding protein C), is the most frequently mutated HCM gene.

    Methods And Results: We evaluated autophagy in patients with HCM carrying mutations and in a -targeted knockin HCM mouse model, as well as the effect of autophagy modulators on the development of cardiomyopathy in knockin mice. Read More

    A review of craniofacial and dental findings of the RASopathies.
    Orthod Craniofac Res 2017 Jun;20 Suppl 1:32-38
    Department of Orofacial Sciences and Program in Craniofacial Biology, University of California, San Francisco, San Francisco, CA, USA.
    Objectives: The RASopathies are a group of syndromes that have in common germline mutations in genes that encode components of the Ras/mitogen-activated protein kinase (MAPK) pathway and have been a focus of study to understand the role of this pathway in development and disease. These syndromes include Noonan syndrome (NS), Noonan syndrome with multiple lentigines (NSML or LEOPARD syndrome), neurofibromatosis type 1 (NF1), Costello syndrome (CS), cardio-facio-cutaneous (CFC) syndrome, neurofibromatosis type 1-like syndrome (NFLS or Legius syndrome) and capillary malformation-arteriovenous malformation syndrome (CM-AVM). These disorders affect multiple systems, including the craniofacial complex. Read More

    [Overlap syndrome. LEOPARD and neurofibromatosis. A case report].
    Rev Med Inst Mex Seguro Soc 2017 Jul-Aug;55(4):540-543
    Servicio de Terapia Intensiva, Hospital General de Zona 30 "Iztacalco", Instituto Mexicano del Seguro Social, Ciudad de México, México.
    We expose a clinical case of a 43-year-old patient who was attended at the Dermatology service in a general hospital of the Instituto Mexicano del Seguro Social, with a disseminated pattern of lentigines, psychomotor retardation and electrocardiographic abnormalities. Afterwards, we made an analysis of the literature. Read More

    In vivo efficacy of the AKT inhibitor ARQ 092 in Noonan Syndrome with multiple lentigines-associated hypertrophic cardiomyopathy.
    PLoS One 2017 5;12(6):e0178905. Epub 2017 Jun 5.
    Department of Medicine, Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
    Noonan Syndrome with Multiple Lentigines (NSML, formerly LEOPARD syndrome) is an autosomal dominant "RASopathy" disorder manifesting in congenital heart disease. Most cases of NSML are caused by catalytically inactivating mutations in the protein tyrosine phosphatase (PTP), non-receptor type 11 (PTPN11), encoding the SH2 domain-containing PTP-2 (SHP2) protein. We previously generated knock-in mice harboring the PTPN11 mutation Y279C, one of the most common NSML alleles; these now-termed SHP2Y279C/+ mice recapitulate the human disorder and develop hypertrophic cardiomyopathy (HCM) by 12 weeks of age. Read More

    [Update on the treatment of RASopathies].
    Rev Neurol 2017 May;64(s03):S13-S17
    Hospital Infantil Universitario Nino Jesus, 28009 Madrid, Espana.
    Introduction: The term 'RASopathies' covers a series of diseases that present mutations in the genes that code for the proteins of the RAS/MAPK pathway. These diseases include neurofibromatosis type 1, Noonan syndrome, Legius syndrome, LEOPARD syndrome, Costello syndrome and cardiofaciocutaneous syndrome. Involvement of the RAS/MAPK pathway not only increases predisposition to develop tumours, but also determines the presence of phenotypic anomalies and alterations in learning processes. Read More

    Cochlear implantation and clinical features in patients with Noonan syndrome and Noonan syndrome with multiple lentigines caused by a mutation in PTPN11.
    Int J Pediatr Otorhinolaryngol 2017 Jun 17;97:228-234. Epub 2017 Apr 17.
    Department of Otorhinolaryngology, Head and Neck Surgery, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
    Existing literature only reports a few patients with Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML) who underwent cochlear implantation (CI). The present study describes four NS patients and one NSML patient with a PTPN11 mutation. They all had severe to profound hearing loss, and they received a CI. Read More

    Do you know this syndrome? Leopard syndrome.
    An Bras Dermatol 2017 Jan-Feb;92(1):127-129
    Odontology Department of the Pontifícia Universidade Católica de Minas Gerais (PUC Minas) - Belo Horizonte (MG), Brazil.
    Hypertrophic cardiomyopathy is known as Leopard syndrome, which is a mnemonic rule for multiple lentigines (L), electrocardiographic conduction abnormalities (E), ocular hypertelorism (O), pulmonary stenosis (P), abnormalities of genitalia (A), retardation of growth (R), and deafness (D). We report the case of a 12-year-old patient with some of the abovementioned characteristics: hypertelorism, macroglossia, lentigines, hypospadias, cryptorchidism, subaortic stenosis, growth retardation, and hearing impairment. Due to this set of symptoms, we diagnosed Leopard syndrome. Read More

    Common Skin Conditions in Children: Noninfectious Rashes.
    FP Essent 2017 Feb;453:18-25
    University of North Carolina Chapel Hill School of Medicine Dermatology Residency Program, 410 Market St. Suite 400 CB#7715, Chapel Hill, NC 27516.
    Cutaneous adverse drug reactions are among the most common noninfectious rashes of childhood. Cutaneous adverse drug reactions are classified as morbilliform, urticarial, bullous, pustular, or psoriasiform. Atopic dermatitis is one of the most common inflammatory cutaneous eruptions, and is characterized by pruritus and flexural distribution. Read More

    Noonan syndrome - a new survey.
    Arch Med Sci 2017 Feb 19;13(1):215-222. Epub 2016 Dec 19.
    Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
    Noonan syndrome (NS) is an autosomal dominant disorder with vast heterogeneity in clinical and genetic features. Various symptoms have been reported for this abnormality such as short stature, unusual facial characteristics, congenital heart abnormalities, developmental complications, and an elevated tumor incidence rate. Noonan syndrome shares clinical features with other rare conditions, including LEOPARD syndrome, cardio-facio-cutaneous syndrome, Noonan-like syndrome with loose anagen hair, and Costello syndrome. Read More

    Sequence variation in results in a novel form of cardio-cutaneous syndrome.
    EMBO Mol Med 2017 03;9(3):319-336
    Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel
    Dilated cardiomyopathy (DCM) is a life-threatening disorder whose genetic basis is heterogeneous and mostly unknown. Five Arab Christian infants, aged 4-30 months from four families, were diagnosed with DCM associated with mild skin, teeth, and hair abnormalities. All passed away before age 3. Read More

    Modeling RASopathies with Genetically Modified Mouse Models.
    Methods Mol Biol 2017 ;1487:379-408
    Molecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), Melchor Fernández Almagro 3, 28029, Madrid, Spain.
    The RAS/MAPK signaling pathway plays key roles in development, cell survival and proliferation, as well as in cancer pathogenesis. Molecular genetic studies have identified a group of developmental syndromes, the RASopathies, caused by germ line mutations in this pathway. The syndromes included within this classification are neurofibromatosis type 1 (NF1), Noonan syndrome (NS), Noonan syndrome with multiple lentigines (NS-ML, formerly known as LEOPARD syndrome), Costello syndrome (CS), cardio-facio-cutaneous syndrome (CFC), Legius syndrome (LS, NF1-like syndrome), capillary malformation-arteriovenous malformation syndrome (CM-AVM), and hereditary gingival fibromatosis (HGF) type 1. Read More

    Molecular screening strategies for NF1-like syndromes with café-au-lait macules (Review).
    Mol Med Rep 2016 Nov 22;14(5):4023-4029. Epub 2016 Sep 22.
    Department of Dermatology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
    Multiple café-au-lait macules (CALM) are usually associated with neurofibromatosis type 1 (NF1), one of the most common hereditary disorders. However, a group of genetic disorders presenting with CALM have mutations that are involved in human skin pigmentation regulation signaling pathways, including KIT ligand/KIT proto‑oncogene receptor tyrosine kinase and Ras/mitogen‑activated protein kinase. These disorders, which include Legius syndrome, Noonan syndrome with multiple lentigines or LEOPARD syndrome, and familial progressive hyperpigmentation) are difficult to distinguish from NF1 at early stages, using skin appearance alone. Read More

    Phenotypic predictors and final diagnoses in patients referred for RASopathy testing by targeted next-generation sequencing.
    Genet Med 2017 Jun 20;19(6):715-718. Epub 2016 Oct 20.
    Division of Genomic Diagnostics and Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
    Introduction: RASopathies include disorders generally characterized by developmental delay, specific heart defects, short stature, cardiac hypertrophy, and facial dysmorphisms. Next-generation sequencing (NGS)-based panels have widespread acceptance as a diagnostic tool for RASopathies.

    Materials And Methods: The first 126 patients evaluated by clinical examination and the NGS RASopathy panel at the Children's Hospital of Philadelphia were enrolled. Read More

    The experience of bilateral cochlear implantation in a child with LEOPARD syndrome.
    Int J Pediatr Otorhinolaryngol 2016 Nov 14;90:125-127. Epub 2016 Sep 14.
    Dept of Otolaryngology, Long Island Jewish Medical Center, NY, USA.
    We present a 3-year old boy with Leopard syndrome. His clinical manifestations included a congenital bilateral sensorineural hearing loss. He underwent cochlear implantation on the right side at age 1 year and on the left side at age 1. Read More

    Lentiginous phenotypes caused by diverse pathogenic genes (SASH1 and PTPN11): clinical and molecular discrimination.
    Clin Genet 2016 Oct 3;90(4):372-7. Epub 2016 Feb 3.
    Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
    Pathogenic mutations in genes (SASH1 and PTPN11) can cause a rare genetic disorder associated with pigmentation defects and the well-known LEOPARD syndrome, respectively. Both conditions presented with lentiginous phenotypes. The aim of this study was to arrive at definite diagnoses of three Chinese boys with clinically suspected lentigines-related syndromes. Read More

    Variations in Multiple Syndromic Deafness Genes Mimic Non-syndromic Hearing Loss.
    Sci Rep 2016 08 26;6:31622. Epub 2016 Aug 26.
    John P. Hussman Institute for Human Genomics, University of Miami, Miami, 33136, FL, USA.
    The genetics of both syndromic (SHL) and non-syndromic hearing loss (NSHL) is characterized by a high degree of genetic heterogeneity. We analyzed whole exome sequencing data of 102 unrelated probands with apparently NSHL without a causative variant in known NSHL genes. We detected five causative variants in different SHL genes (SOX10, MITF, PTPN11, CHD7, and KMT2D) in five (4. Read More

    Identification of a PTPN11 hot spot mutation in a child with atypical LEOPARD syndrome.
    Mol Med Rep 2016 Sep 27;14(3):2639-43. Epub 2016 Jul 27.
    Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200092, P.R. China.
    LEOPARD syndrome (LS) is an autosomal dominant inherited disorder primarily caused by mutations in the PTPN11, RAF1 and BRAF genes. Characteristic features include lentigines, craniofacial dysmorphism, myocardium or valve abnormalities, eletrocardiographic conduction defects and deafness. LS, neurofibromatosis type 1, Noonan syndrome and Legius syndrome are a group of highly overlapped disorders termed 'RASopathies'. Read More

    Male fertility and skin diseases.
    Rev Endocr Metab Disord 2016 09;17(3):353-365
    Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany.
    Male fertility can be affected by a variety of organs diseases, including the skin. Several genodermatoses affect the skin and several other organs including the male reproductive system, commonly in the form of cryptorchidism and hypogonadism. The most relevant syndromes are associated with dyschromias, such as deSanctis-Cacchione, poikiloderma congenital, LEOPARD, and H syndrome; others with ichthyosis, such as Rud, and trichothiodystrophy; or a group of unrelated genodermatoses, such as ablepharon macrostomia, Coffin-Siris, Gorlin-Goltz, and Werner. Read More

    Multiple giant cell lesions in a patient with Noonan syndrome with multiple lentigines.
    Eur J Med Genet 2016 Aug 26;59(8):425-8. Epub 2016 May 26.
    Department of Oral and Maxillofacial Surgery, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
    A patient with Noonan syndrome with multiple lentigines (NSML) and multiple giant cell lesions (MGCL) in mandibles and maxillae is described. A mutation p.Thr468Met in the PTPN11-gene was found. Read More

    [The Biological Function of SHP2 in Human Disease].
    Mol Biol (Mosk) 2016 Jan-Feb;50(1):27-33
    Department of Laboratory Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, 250014 China.
    Tyrosyl phosphorylation participates in various pathological and physiological processes, which are regulated by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). The Src homology-2 domain containing phosphatase SHP2 (encoded by PTPN11) is an important phosphatase, which was found to be implicated in the regulation of genetic disease, development, metabolic, neurological, muscle, skeletal disease and cancer. Germline mutations in PTPN11 cause the Noonan Syndrome, LEOPARD syndrome and metachondromatosis. Read More

    An Update on Neurofibromatosis Type 1: Not Just Café-au-Lait Spots, Freckling, and Neurofibromas. An Update. Part I. Dermatological Clinical Criteria Diagnostic of the Disease.
    Actas Dermosifiliogr 2016 Jul-Aug;107(6):454-64. Epub 2016 Mar 12.
    Servicio de Neurología, Hospital Infantil del Niño Jesús, Madrid, España.
    Neurofibromatosis type 1 (NF1) is the most common neurocutaneous syndrome and probably the one best known to dermatologists, who are generally the first physicians to suspect its diagnosis. Although the genetic locus of NF1 was identified on chromosome 17 in 1987, diagnosis of the disease is still mainly based on clinical observations and the diagnostic criteria of the National Institute of Health, dating from 1988. Cutaneous manifestations are particularly important because café-au-lait spots, freckling on flexural areas, and cutaneous neurofibromas comprise 3 of the 7 clinical diagnostic criteria. Read More

    Determination of the catalytic activity of LEOPARD syndrome-associated SHP2 mutants toward parafibromin, a bona fide SHP2 substrate involved in Wnt signaling.
    Biochem Biophys Res Commun 2016 Jan 29;469(4):1133-9. Epub 2015 Dec 29.
    Division of Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address:
    SHP2, encoded by the PTPN11 gene, is a protein tyrosine phosphatase that plays a key role in the proliferation of cells via RAS-ERK activation. SHP2 also promotes Wnt signaling by dephosphorylating parafibromin. Germline missense mutations of PTPN11 are found in more than half of patients with Noonan syndrome (NS) and LEOPARD syndrome (LS), both of which are congenital developmental disorders with multiple common symptoms. Read More

    [Leukonychia totalis].
    Hautarzt 2016 Apr;67(4):308-10
    Klinik für Dermatologie, Allergologie und Phlebologie, Klinikum Bremerhaven Reinkenheide, Postbrookstr. 103, 27574, Bremerhaven, Deutschland.
    Our patient presented with leukonychia totalis at the age of 15 years. Other malformations such as syndromes or underlying internal diseases did not exist. The patient's family history was unremarkable. Read More

    LEOPARD Syndrome.
    Dermatol Online J 2015 Oct 16;21(10). Epub 2015 Oct 16.
    R.G.Kar Medical College, Kolkata.
    LEOPARD syndrome (LS) is an autosomal dominantly inherited or sporadic disorder of variable penetrance and expressivity. The acronym LEOPARD stands for its cardinal clinical features including Lentigines, Electrocardiographic conduction abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormalities of genitalia, Retardation of growth, and Deafness. We present herein a patient with LEOPARD syndrome and distinctive features. Read More

    LEOPARD Syndrome with Patent Ductus Arteriosus and Hypertrophic Cardiomyopathy.
    J Assoc Physicians India 2015 May;63(5):76-7
    A sixteen year old girl presented with history of hemoptysis of one week duration. She had history of dyspnea on exertion and frequent respiratory infections in childhood. She had short stature, hypertelorism, neurofibroma, café au lait spots and multiple lentigines. Read More

    Mutation in NRAS in familial Noonan syndrome--case report and review of the literature.
    BMC Med Genet 2015 Oct 14;16:95. Epub 2015 Oct 14.
    Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden.
    Background: Noonan syndrome (NS), a heterogeneous developmental disorder associated with variable clinical expression including short stature, congenital heart defect, unusual pectus deformity and typical facial features, is caused by activating mutations in genes involved in the RAS-MAPK signaling pathway.

    Case Presentation: Here, we present a clinical and molecular characterization of a small family with Noonan syndrome. Comprehensive mutation analysis of NF1, PTPN11, SOS1, CBL, BRAF, RAF1, SHOC2, MAP2K2, MAP2K1, SPRED1, NRAS, HRAS and KRAS was performed using targeted next-generation sequencing. Read More

    Recent advances in RASopathies.
    J Hum Genet 2016 Jan 8;61(1):33-9. Epub 2015 Oct 8.
    National Research Institute for Child Health and Development, Tokyo, Japan.
    RASopathies or RAS/mitogen-activated protein kinase (MAPK) syndromes are a group of phenotypically overlapping syndromes caused by germline mutations that encode components of the RAS/MAPK signaling pathway. These disorders include neurofibromatosis type I, Legius syndrome, Noonan syndrome, Noonan syndrome with multiple lentigines (formerly called LEOPARD syndrome), Costello syndrome, cardiofaciocutaneous (CFC) syndrome, Noonan-like syndrome, hereditary gingival fibromatosis and capillary malformation-arteriovenous malformation. Recently, novel gene variants, including RIT1, RRAS, RASA2, A2ML1, SOS2 and LZTR1, have been shown to be associated with RASopathies, further expanding the disease entity. Read More

    Generalized lentiginosis in an 11 year old boy.
    Dermatol Online J 2015 Sep 17;21(9). Epub 2015 Sep 17.
    First Affiliated Hospital of Nanjing Medical University.
    Generalized lentiginosis refers to generalized lentigines without systemic abnormalities, characterized by multiple brown or black macules owing to increased proliferation of melanocytes. There are also lentiginosis syndromes associated with systemic abnormalities such as Peutz-Jeghers syndrome, Leopard syndrome, and Carney complex. Generalized lentiginosis can be diagnosis by patient's history, physical and laboratory examination, and histopathology. Read More

    Phenotypical diversity of patients with LEOPARD syndrome carrying the worldwide recurrent p.Tyr279Cys PTPN11 mutation.
    Arch Dermatol Res 2015 Dec 16;307(10):891-5. Epub 2015 Sep 16.
    MTA-SZTE Dermatological Research Group, University of Szeged, Szeged, Hungary.
    LEOPARD syndrome (LS, OMIM 151100) is a rare monogenic disorder. The name is an acronym of its major features such as multiple lentigines, electrocardiographic conduction defects, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retardation of growth and sensorineural deafness. LS develops due to mutations in the protein-tyrosine phosphatase nonreceptor-type 11, PTPN11. Read More

    Paraspinal neurofibromas and hypertrophic neuropathy in Noonan syndrome with multiple lentigines.
    J Med Genet 2016 Feb 2;53(2):123-6. Epub 2015 Sep 2.
    Department of Medical Genetics, Mayo Clinic, Rochester, Minnesota, USA Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
    Background: Noonan syndrome with multiple lentigines (NSML), formerly known as LEOPARD syndrome, is an autosomal-dominant disorder characterised by lentigines, EKG abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, growth retardation and deafness. There is significant clinical overlap between NSML and other disorders that result from dysregulated rat sarcoma/mitogen-activated protein kinase pathway (RASopathies). Except for neurofibromatosis type 1, other RASopathies are not known to be typically associated with neurogenic tumours. Read More

    Peripheral blood cells from children with RASopathies show enhanced spontaneous colonies growth in vitro and hyperactive RAS signaling.
    Blood Cancer J 2015 Jul 17;5:e324. Epub 2015 Jul 17.
    Pediatrics Clinical Genetics, MBBM-AO San Gerardo Foundation, University of Milano-Bicocca, Monza, Italy.
    Germline mutations in genes coding for molecules involved in the RAS/RAF/MEK/ERK pathway are the hallmarks of a newly classified family of autosomal dominant syndromes termed RASopathies. Myeloproliferative disorders (MPDs), in particular, juvenile myelomonocytic leukemia, can lead to potentially severe complications in children with Noonan syndrome (NS). We studied 27 children with NS or other RASopathies and 35 age-matched children as control subjects. Read More

    BRAF gene: From human cancers to developmental syndromes.
    Saudi J Biol Sci 2015 Jul 23;22(4):359-73. Epub 2014 Oct 23.
    Faculty of Genetic Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
    The BRAF gene encodes for a serine/threonine protein kinase that participates in the MAPK/ERK signalling pathway and plays a vital role in cancers and developmental syndromes (RASopathies). The current review discusses the clinical significance of the BRAF gene and other members of RAS/RAF cascade in human cancers and RAS/MAPK syndromes, and focuses the molecular basis and clinical genetics of BRAF to better understand its parallel involvement in both tumourigenesis and RAS/MAPK syndromes-Noonan syndrome, cardio-facio-cutaneous syndrome and LEOPARD syndrome. Read More

    Functions of Shp2 in cancer.
    J Cell Mol Med 2015 Sep 19;19(9):2075-83. Epub 2015 Jun 19.
    Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
    Diagnostics and therapies have shown evident advances. Tumour surgery, chemotherapy and radiotherapy are the main techniques in treat cancers. Targeted therapy and drug resistance are the main focus in cancer research, but many molecular intracellular mechanisms remain unknown. Read More

    SHP2-Deficiency in Chondrocytes Deforms Orofacial Cartilage and Ciliogenesis in Mice.
    J Bone Miner Res 2015 Nov 28;30(11):2028-32. Epub 2015 Jul 28.
    Department of Pediatrics, The University of Texas Medical School at Houston, Houston, TX, USA.
    Congenital orofacial abnormalities are clinically seen in human syndromes with SHP2 germline mutations such as LEOPARD and Noonan syndrome. Recent studies demonstrate that SHP2-deficiency leads to skeletal abnormalities including scoliosis and cartilaginous benign tumor metachondromatosis, suggesting that growth plate cartilage is a key tissue regulated by SHP2. The role and cellular mechanism of SHP2 in the orofacial cartilage, however, remains unknown. Read More

    Pathogenesis of multiple lentigines in LEOPARD syndrome with PTPN11 gene mutation.
    Acta Derm Venereol 2015 Nov;95(8):978-84
    Department of Dermatology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
    LEOPARD syndrome (LS) is an autosomal dominant condition with multiple anomalies, including multiple lentigines. LS is caused by mutations in PTPN11, encoding the protein tyrosine phosphatase, SHP-2. We report here 2 unrelated Japanese cases of LS with different PTPN11 mutations (p. Read More

    [Arnold-Chiari malformation in Noonan syndrome and other syndromes of the RAS/MAPK pathway].
    Rev Neurol 2015 May;60(9):408-12
    Hospital La Fe, 46009 Valencia, Espana.
    Introduction: Noonan syndrome (NS) and other syndromes with a similar phenotype, such as LEOPARD, cardiofaciocutaneous, Costello and Legius, are associated to mutations in genes included in the RAS/MAPK pathway (RASopathies), which is an important signalling pathway related to cell proliferation. Tonsillar descent into the upper cervical spinal canal, known as Arnold-Chiari malformation (ACM), has been reported in patients with NS and this has led some researchers to suggest that ACM could be part of the phenotypic spectrum of NS. We report two cases of NS and ACM. Read More

    Systemic conditions in children associated with pigmentary changes.
    Clin Dermatol 2015 May-Jun;33(3):362-7. Epub 2014 Dec 8.
    Department of Pediatrics, Indiana University School of Medicine, E3131 Fifth Third Office Building, 720 Eskenazi Avenue, Indianapolis, Indiana, 46202. Electronic address:
    Systemic conditions may have pigmentary associations. Prompt recognition of these associations allows the practitioner to initiate the appropriate workup and therapy when indicated. This contribution highlights some of the clinical features of neurofibromatosis 1, LEOPARD syndrome, acanthosis nigricans, hypomelanosis of Ito, incontinentia pigmenti, CHILD syndrome, and piebaldism to assist the dermatologist in making the proper diagnosis. Read More

    PTPN11 mutation manifesting as LEOPARD syndrome associated with hypertrophic plexi and neuropathic pain.
    BMC Neurol 2015 Apr 16;15:55. Epub 2015 Apr 16.
    Department of Clinical Neurosciences, Lausanne University Hospital (CHUV), Rue du Bugnon 21, 1011, Lausanne, Switzerland.
    Background: LEOPARD syndrome (LS) belongs to the family of neuro-cardio-facio-cutaneous syndromes, which include Neurofibromatosis-1 (NF1), Noonan syndrome, Costello Syndrome, cardio-facio-cutaneous syndrome, Noonan-like syndrome with loose anagen hair and Legius syndrome. These conditions are caused by mutations in genes encoding proteins involved in the RAS-MAPK cellular pathway. Clinical heterogeneity and phenotype overlaps across those different syndromes is already recognized. Read More

    Elevated Ca2+ transients and increased myofibrillar power generation cause cardiac hypercontractility in a model of Noonan syndrome with multiple lentigines.
    Am J Physiol Heart Circ Physiol 2015 May 27;308(9):H1086-95. Epub 2015 Feb 27.
    Department of Medical Pharmacology and Physiology/Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri
    Noonan syndrome with multiple lentigines (NSML) is primarily caused by mutations in the nonreceptor protein tyrosine phosphatase SHP2 and associated with congenital heart disease in the form of pulmonary valve stenosis and hypertrophic cardiomyopathy (HCM). Our goal was to elucidate the cellular mechanisms underlying the development of HCM caused by the Q510E mutation in SHP2. NSML patients carrying this mutation suffer from a particularly severe form of HCM. Read More

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