486 results match your criteria LEOPARD Syndrome

Dermatological manifestations of cardiac conditions.

Br J Cardiol 2022 8;29(1). Epub 2022 Mar 8.

Consultant Cardiologist Department of Cardiology, St. Helens & Knowsley Teaching Hospitals NHS Trust, Whiston, L35 5DR.

Various cardiac disorders seen in general and acute medicine have dermatological manifestations that may provide critical clues to the underlying disease. This review will discuss the important dermatological signs seen in cardiac conditions. We believe greater interdisciplinary liaison will improve our understanding of the link between the dermatological and cardiovascular systems and the underlying disease processes. Read More

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A Case of Bilateral Diffuse Uveal Melanocytic Proliferation in the Setting of Urothelial Carcinoma of the Ureter: A Failed Response to Plasmapheresis.

Ophthalmic Surg Lasers Imaging Retina 2022 06 1;53(6):350-353. Epub 2022 Jun 1.

Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare paraneoplastic syndrome. Diagnosis can be difficult and treatment guidelines are ill-defined. A 73-year-old man with poorly differentiated high grade urothelial carcinoma of the ureter metastatic to the liver, lungs, lymph nodes, and pelvis treated with chemotherapy and immunotherapy reported gradual vision loss. Read More

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Detection of SARS-CoV-2 clade B.1.2 in three snow leopards.

Transbound Emerg Dis 2022 Jun 13. Epub 2022 Jun 13.

Zoological Pathology Program, College of Veterinary Medicine, University of Illinois, Brookfield, Illinois.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of seven coronaviruses known to infect humans. Different from other concerned coronavirus and influenza viruses, SARS-CoV-2 has a higher basic reproduction number and thus transmits more efficiently among hosts. Testing animals for SARS-CoV-2 may help decipher virus reservoirs, transmission and pathogenesis. Read More

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Neurological features of Noonan syndrome and related RASopathies: Pain and nerve enlargement characterized by nerve ultrasound.

Am J Med Genet A 2022 06 8;188(6):1801-1807. Epub 2022 Mar 8.

Department of Neurology and Clinical Neurophysiology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.

This study aimed to assess the nature of peripheral nervous system (PNS) involvement in three patients with Noonan syndrome (NS) or NS with multiple lentigines (NSML) as a related RASopathy, presenting primary with intractable neuropathic pain. We studied three unrelated adult patients with severe neuropathic pain and muscle weakness of the limbs. Nerve conduction studies and needle electromyography (EMG) were performed and PNS involvement was assessed by nerve ultrasound imaging, complemented with spinal magnetic resonance imaging (MRI) for the evaluation of proximal nerve segments. Read More

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Bilateral diffuse uveal melanocytic proliferation: Report of a novel optical coherence tomography finding and clinical response to plasmapheresis.

Am J Ophthalmol Case Rep 2022 Mar 30;25:101349. Epub 2022 Jan 30.

Department of Ophthalmology, Université de Montréal, Montreal, Quebec, Canada.

Purpose: To describe a novel optical coherence tomography (OCT) finding in a case of bilateral diffuse uveal melanocytic proliferation (BDUMP) and to report the clinical response to plasmapheresis.

Observations: We report the case of a 54-year-old man who was being treated with adjuvant immune checkpoint inhibitors for metastatic renal cell carcinoma. He had suffered from bilateral progressive vision loss without ocular pain. Read More

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The RASopathies: Biology, genetics and therapeutic options.

Adv Cancer Res 2022 7;153:305-341. Epub 2021 Aug 7.

Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, United States. Electronic address:

The RASopathies are a group of genetic diseases in which the Ras/MAPK signaling pathway is inappropriately activated as a result of mutations in genes encoding proteins within this pathway. As their causative mutations have been identified, this group of diseases has expanded to include neurofibromatosis type 1 (NF1), Legius syndrome, Noonan syndrome, CBL syndrome, Noonan syndrome-like disorder with loose anagen hair, Noonan syndrome with multiple lentigines, Costello syndrome, cardiofaciocutaneous syndrome, gingival fibromatosis and capillary malformation-arteriovenous malformation syndrome. Many of these genetic disorders share clinical features in common such as abnormal facies, short stature, varying degrees of cognitive impairment, cardiovascular abnormalities, skeletal abnormalities and a predisposition to develop benign and malignant neoplasms. Read More

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Bilateral Diffuse Uveal Melanocytic Proliferation in a Woman with Metastatic Scalp Squamous Cell Carcinoma Treated with Cemiplimab.

Case Rep Ophthalmol 2021 Sep-Dec;12(3):961-966. Epub 2021 Dec 10.

Division of Ophthalmology, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare paraneoplastic intraocular syndrome that causes progressive visual loss in patients driven by an IgG factor associated with an underlying malignancy. The IgG factor - cultured melanocyte elongation and proliferation - was found in the IgG fraction of the serum of BDUMP patients. It has been shown to be involved in melanocytic proliferation. Read More

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December 2021

Spatial epidemiology and genetic diversity of SARS-CoV-2 and related coronaviruses in domestic and wild animals.

PLoS One 2021 15;16(12):e0260635. Epub 2021 Dec 15.

Institute of Epidemiology, Disease Control and Research (IEDCR), Dhaka, Bangladesh.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) showed susceptibility to diverse animal species. We conducted this study to understand the spatial epidemiology, genetic diversity, and statistically significant genetic similarity along with per-gene recombination events of SARS-CoV-2 and related viruses (SC2r-CoVs) in animals globally. We collected a number of different animal species infected with SARS-CoV-2 and its related viruses. Read More

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December 2021

Reverse zoonosis of coronavirus disease-19: Present status and the control by one health approach.

Vet World 2021 Oct 30;14(10):2817-2826. Epub 2021 Oct 30.

Small Animal Facility, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.

The recent coronavirus disease (COVID-19) outbreak is one of its kind in the history of public health that has created a major global threat. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a zoonotic source and hence, reverse zoonosis (disease transmission from humans to animals) increases the risk and rate of SARS-CoV-2 infection. Serological and molecular analyses and experimental infection studies have identified SARS-CoV-2 infection in several animal species in various countries. Read More

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October 2021

Rare Case of Bilateral Diffuse Uveal Melanocytic Proliferation with Dermal and Mucosal Hyperpigmentations.

Diagnostics (Basel) 2021 Nov 5;11(11). Epub 2021 Nov 5.

Department of Ophthalmology, University of Lübeck, University Hospital Schleswig-Holstein, Ratzeburger Allee 160, 23538 Lübeck, Germany.

Purpose: The demonstration of a rare case of bilateral diffuse uveal melanocytic proliferation (BDUMP) due to a lung carcinoma with unusual dermal lesions.

Case Description: A 76-year-old man with painless bilateral vision loss revealed leopard or giraffe spot chorioretinopathy and bilateral serous retinal detachment. Ultrasound biomicroscopy revealed uveal swelling expanding into the anterior chamber angle. Read More

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November 2021

SARS-CoV-2 vaccine for domestic and captive animals: An effort to counter COVID-19 pandemic at the human-animal interface.

Vaccine 2021 12 6;39(49):7119-7122. Epub 2021 Nov 6.

Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India. Electronic address:

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has already affected millions worldwide. The emergence of multiple SARS-CoV-2 variants may pose a significant threat to our efforts in controlling the pandemic. The impact of SARS-CoV-2 variants on the efficacy of available vaccines, therapeutics, and diagnostics is currently being investigated. Read More

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December 2021

Hypertrophic Cardiomyopathy in RASopathies: Diagnosis, Clinical Characteristics, Prognostic Implications, and Management.

Heart Fail Clin 2022 Jan 25;18(1):19-29. Epub 2021 Oct 25.

Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", Naples; Division of Cardiology, A.O.R.N. "Sant'Anna & San Sebastiano", Caserta I-81100, Italy. Electronic address:

RASopathies are multisystemic disorders caused by germline mutations in genes linked to the RAS/mitogen-activated protein kinase pathway. Diagnosis of RASopathy can be triggered by clinical clues ("red flags") which may direct the clinician toward a specific gene test. Compared with sarcomeric hypertrophic cardiomyopathy, hypertrophic cardiomyopathy in RASopathies (R-HCM) is associated with higher prevalence of congestive heart failure and shows increased prevalence and severity of left ventricular outflow tract obstruction. Read More

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January 2022

The First Vietnamese Patient of LEOPARD Syndrome due to a Mutation: A Case Report and Review of the Literature.

Case Rep Genet 2021 13;2021:8197435. Epub 2021 Sep 13.

Ho Chi Minh City Hospital of Dermato-Venereology, Ho Chi Minh City, Vietnam.

LEOPARD syndrome is a rare congenital anomaly that involves several organs. Patients with this syndrome develop multiple lentigines resembling a leopard's hide. LEOPARD is an acronym of the major features constituting the syndrome including lentigines, electrocardiographic conduction defects, ocular hypertelorism, pulmonary valve stenosis, anomalies of genitalia, retardation of growth, and deafness. Read More

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September 2021

Leopard syndrome: the potential cardiac defect underlying skin phenotypes.

Hereditas 2021 Sep 6;158(1):34. Epub 2021 Sep 6.

The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, No. 3333, Binsheng Road, Binjiang District, Hangzhou, Zhejiang, China.

LEOPARD syndrome (OMIM #151,100) caused by a germline PTPN11 mutation are characterized as multisystemic anomalies and variable marked phenotypes such as multiple lentigines and cafe´-au-lait spots, electrocardiographic conduction abnormalities, ocular hypertelorism/obstructive cardiomyopathy, pulmonary stenosis, abnormal genitalia, retardation of growth, and deafness. Phenotype overlap complicates clinical discrimination within RASopathies, making the diagnosis of LEOPARD more confusing and challenging. Besides, LEOPARD patients do not usually present with all these typical clinical features, increasing the possibility of underdiagnosis or misdiagnosis. Read More

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September 2021

[Comparison of biometric and structural ocular manifestations of Marfan syndrome in twins].

Q He R H Wei

Zhonghua Yan Ke Za Zhi 2021 Jul;57(7):540-543

Tianjin Medical University Eye Hospital, Eye Institute and School of Optometry, Tianjin Branch of National Clinical Research Center for Ocular Disease, Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin 300384, China.

A pair of 16-year-old twin brothers presented to our hospital. The younger brother had been losing vision in his left eye for 6 months, and the older brother had been losing vision in both eyes for 6 months. Both patients were 2. Read More

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Central Serous Chorioretinopathy mimicking Idiopathic Uveal Effusion Syndrome.

Retin Cases Brief Rep 2021 Jun 1. Epub 2021 Jun 1.

Université de Paris, Ophthalmology Department, APHP, Hôpital Lariboisière, F-75010, Paris, France Centre d'Imagerie et Laser, F-75015, Paris, France.

Purpose: To describe central serous chorioretinopathy (CSCR) cases presenting as uveal effusion syndrome, providing new insights into "pachychoroid spectrum" diseases.

Methods: Clinical charts, color fundus photographs, fluorescein angiography, indocyanine green angiography, optical coherence tomography, ultrasound imaging, cerebral magnetic resonance imaging and biometry of four eyes of three patients were assessed. A literature review was conducted. Read More

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50 Years Ago in TheJournalofPediatrics: Multiple Lentigines Syndrome: Historical Perspective and Contributions of Dr David W. Smith.

J Pediatr 2021 06;233:211

Division of Human Genetics and Roberts Individualized Medical Genetics Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

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Noncanonical crRNAs derived from host transcripts enable multiplexable RNA detection by Cas9.

Science 2021 05 27;372(6545):941-948. Epub 2021 Apr 27.

Helmholtz Institute for RNA-based Infection Research (HIRI)/Helmholtz-Centre for Infection Research (HZI), 97080 Würzburg, Germany.

CRISPR-Cas systems recognize foreign genetic material using CRISPR RNAs (crRNAs). In type II systems, a trans-activating crRNA (tracrRNA) hybridizes to crRNAs to drive their processing and utilization by Cas9. While analyzing Cas9-RNA complexes from , we discovered tracrRNA hybridizing to cellular RNAs, leading to formation of "noncanonical" crRNAs capable of guiding DNA targeting by Cas9. Read More

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LEPOARD syndrome: A report of a case with a novel PTPN11 mutation.

JAAD Case Rep 2021 May 20;11:57-59. Epub 2021 Mar 20.

Department of Dermatology, Ha'emek Medical Center, Afula, Israel.

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A multifunctional cross-validation high-throughput screening protocol enabling the discovery of new SHP2 inhibitors.

Acta Pharm Sin B 2021 Mar 31;11(3):750-762. Epub 2020 Oct 31.

School of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou 450001, China.

The protein tyrosine phosphatase Src homology phosphotyrosyl phosphatase 2 (SHP2) is implicated in various cancers, and targeting SHP2 has become a promising therapeutic approach. We herein described a robust cross-validation high-throughput screening protocol that combined the fluorescence-based enzyme assay and the conformation-dependent thermal shift assay for the discovery of SHP2 inhibitors. The established method can effectively exclude the false positive SHP2 inhibitors with fluorescence interference and was also successfully employed to identify new protein tyrosine phosphatase domain of SHP2 (SHP2-PTP) and allosteric inhibitors. Read More

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Noonan Syndrome with Multiple Lentigines and Mutation: A Case with Intracerebral Hemorrhage.

Mol Syndromol 2021 Mar 27;12(1):57-63. Epub 2021 Jan 27.

Research Group in Neurosciences (NEUROS), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia.

Noonan syndrome with multiple lentigines (NSML), previously known as LEOPARD syndrome, is a rare autosomal dominant disorder with an unknown prevalence. Characteristics of this disease include cutaneous, neurologic, and cardiologic abnormalities. In this case report, we present a 12-year-old girl who was admitted to the emergency department for acute-onset left weakness, unsteady gait, nausea, and vomiting. Read More

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Multimodal imaging to aid in diagnosis of uveal effusion syndrome type 3.

BMJ Case Rep 2021 Mar 2;14(3). Epub 2021 Mar 2.

Advanced eye centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India

A 47-year-old man presented to our retina clinic with gradual onset diminution of vision in his right eye for the last 3 months. Anterior segment evaluation was normal in both eyes. Fundus evaluation showed the presence of leopard spot appearance in the right eye with inferior exudative retinal detachment. Read More

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Leopard-like retinopathy and severe early-onset portal hypertension expand the phenotype of KARS1-related syndrome: a case report.

BMC Med Genomics 2021 01 21;14(1):25. Epub 2021 Jan 21.

Medical Genetics Unit, Meyer Children's University Hospital, Florence, Italy.

Background: Mutations in lysyl-tRNA synthetase (KARS1), an enzyme that charges tRNA with the amino acid lysine in both the cytoplasm and mitochondria, have been associated thus far with autosomal recessive Charcot-Marie-Tooth type CMTRIB, hearing loss type DFNB89, and mitochondrial encephalohepatopathy (MEH) featuring neurodevelopmental disorders with microcephaly, white matter changes, and cardiac and hepatic failure in less than 30 patients.

Case Presentation: We report the clinical, biochemical and molecular findings of a 14-month-old girl with severe MEH compatible clinical features, profound sensorineural hearing loss, leopard spot retinopathy, pancytopenia, and advanced liver disease with portal hypertension leading to death at the age of 30 months.

Conclusions: Whole exome sequencing identified two rare variants in KARS1 gene. Read More

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January 2021

Compound heterozygosity for PTPN11 variants in a subject with Noonan syndrome provides insights into the mechanism of SHP2-related disorders.

Clin Genet 2021 03 4;99(3):457-461. Epub 2021 Jan 4.

Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.

The RASopathies are a family of clinically related disorders caused by mutations affecting genes participating in the RAS-MAPK signaling cascade. Among them, Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML) are allelic conditions principally associated with dominant mutations in PTPN11, which encodes the nonreceptor SH2 domain-containing protein tyrosine phosphatase SHP2. Individual PTPN11 mutations are specific to each syndrome and have opposite consequences on catalysis, but all favor SHP2's interaction with signaling partners. Read More

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Genotype-phenotype association by echocardiography offers incremental value in patients with Noonan Syndrome with Multiple Lentigines.

Pediatr Res 2021 08 14;90(2):444-451. Epub 2020 Dec 14.

Division of Cardiology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.

Background: Noonan Syndrome with Multiple Lentigines (NSML) and Noonan Syndrome (NS) can be difficult to differentiate clinically in early childhood. This study aims to describe characteristics of the ventricular septum that may differentiate NSML from NS. We hypothesize that the shape of the ventricular septum determined by echocardiography correlates with genotype and may distinguish patients with NSML from those with NS. Read More

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Allosteric Inhibitors of SHP2: An Updated Patent Review (2015-2020).

Curr Med Chem 2021 ;28(19):3825-3842

Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, No. 22, Qixiangtai Road, Heping District, Tianjin 300070, China.

Srchomology-2-domain-containing PTP 2 (SHP2) is a nonreceptor phosphatase encoded by the PTPN11 gene. Over expression of SHP2 is associated with various human diseases, such as Noonan syndrome, LEOPARD syndrome, and cancers. To overcome the shortcomings of existing orthosteric inhibitors, novel inhibitors targeting the allosteric site of SHP2 with high selectivity and low toxicity are under development. Read More

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Introduction to phacomatoses (neurocutaneous disorders) in childhood.

Childs Nerv Syst 2020 10 17;36(10):2229-2268. Epub 2020 Sep 17.

Pediatric Neurosurgery, International Neuroscience Institute [INI], Hanover, Germany.

The Dutch ophthalmologist, Jan van der Hoeve, first introduced the terms phakoma/phakomata (from the old Greek word "ϕαχοσ" = lentil, spot, lens-shaped) to define similar retinal lesions recorded in tuberous sclerosis (1920) and in neurofibromatosis (1923). He later applied this concept: (a) to similar lesions in other organs (e.g. Read More

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October 2020

Phosphatase-independent functions of SHP2 and its regulation by small molecule compounds.

Wenjie Guo Qiang Xu

J Pharmacol Sci 2020 Nov 3;144(3):139-146. Epub 2020 Aug 3.

State Key Laboratory of Pharmaceutical Biotechnology and Collaborative Innovation Center of Chemistry for Life Sciences, School of Life Sciences, Nanjing University, Nanjing, 210093, China. Electronic address:

SHP2 is a non-receptor protein tyrosine phosphatase encoded by the PTPN11 gene in human. Clinically, SHP2 has been identified as a causal factor of several diseases, such as Noonan syndrome, LEOPARD syndrome as well as myeloid malignancies. Interestingly, both loss-of-function and gain-of-function mutations occur in the PTPN11 gene. Read More

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November 2020

Familial LEOPARD Syndrome With Hypertrophic Cardiomyopathy.

Am J Cardiol 2020 11 28;135:168-173. Epub 2020 Aug 28.

Aurora Cardiovascular and Thoracic Services, Aurora Sinai/Aurora St. Luke's Medical Centers, University of Wisconsin School of Medicine and Public Health, Milwaukee, Wisconsin. Electronic address:

Multiple lentigines syndrome is an autosomal dominant inherited condition with variable expressivity that is also known as LEOPARD syndrome. LEOPARD stands for lentigines, electrocardiographic conduction defects, ocular hypertelorism, pulmonary valve stenosis, abnormalities of genitalia, retardation of growth, and deafness. LEOPARD syndrome most frequently develops secondary to a missense mutation of protein-tyrosine phosphatase nonreceptor type 11 gene, which encodes tyrosine phosphatase. Read More

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November 2020