LEOPARD Syndrome
Noonan Syndrome
Neurofibromatoses
Protein Tyrosine Phosphatase, Non-Receptor Type 11
Lentigo
Pulmonary Subvalvular Stenosis
Panthera
Felidae
Carnivora
Encyclopedias as Topic
Hutchinson's Melanotic Freckle
LEOPARD syndrome: a new polyaneurysm association and an update on the molecular genetics of the disease. (1/34)
LEOPARD syndrome, one of many cardiocutaneous syndromes, is an acronym for some of the obvious manifestations of the disease, such as lentigines or ocular hypertelorism. The synonymous name progressive cardiomyopathic lentiginosis better indicates the morbid cardiac features that patients with the syndrome have. A patient with LEOPARD syndrome is presented. He had recurrent upper extremity aneurysms requiring multiple operations and finally PTFE reinforced venous grafts to prevent further aneurysmal degeneration. He has multiple other peripheral aneurysms, thus far asymptomatic. His diagnosis of LEOPARD syndrome was confirmed on a genetic basis. Review of the literature reveals no previous reports of severe aneurysmal disease in these patients. (+info)A novel PTPN11 gene mutation bridges Noonan syndrome, multiple lentigines/LEOPARD syndrome and Noonan-like/multiple giant cell lesion syndrome. (2/34)
Noonan (NS) and multiple lentigines/LEOPARD syndromes (LS) have proved to be associated with distinct PTPN11 mutations. Noonan-like/multiple giant cell lesion syndrome (NLS) is a rare disease, characterised by short stature, facial dysmorphisms, congenital heart defect (CHD) and central giant cell lesions. PTPN11 gene mutations have been reported in a single NLS family and two sporadic patients. Here we report a patient with a complex phenotype progressing throughout the years from NS at birth towards LS and NLS. PTPN11 gene analysis disclosed a novel missense mutation (Ala461Thr) in exon 12, affecting the consensus sequence of the SHP2-active site. This observation joins together NS and LS to NLS into a unique genetic defect, broadening the clinical and molecular spectrum of PTPN11-related disorders. (+info)LEOPARD syndrome and hypertrophic obstructive cardiomyopathy: a case report. (3/34)
The LEOPARD syndrome is a rare, autosomal dominant multisystemic disorder characterized by lentiginosis, ocular hypertelorism, abnormal genitalia, growth retardation, sensorineural deafness, and cardiac and electrocardiographic abnormalities. Although it is not cited, hypertrophic cardiomyopathy is often associated with the disease. In this study, we present a nine-year-old boy with LEOPARD syndrome and hypertrophic obstructive cardiomyopathy. (+info)Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease. (4/34)
Germline mutations in PTPN11, the gene encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome (NS) and the clinically related LEOPARD syndrome (LS), whereas somatic mutations in the same gene contribute to leukemogenesis. On the basis of our previously gathered genetic and biochemical data, we proposed a model that splits NS- and leukemia-associated PTPN11 mutations into two major classes of activating lesions with differential perturbing effects on development and hematopoiesis. To test this model, we investigated further the diversity of germline and somatic PTPN11 mutations, delineated the association of those mutations with disease, characterized biochemically a panel of mutant SHP-2 proteins recurring in NS, LS, and leukemia, and performed molecular dynamics simulations to determine the structural effects of selected mutations. Our results document a strict correlation between the identity of the lesion and disease and demonstrate that NS-causative mutations have less potency for promoting SHP-2 gain of function than do leukemia-associated ones. Furthermore, we show that the recurrent LS-causing Y279C and T468M amino acid substitutions engender loss of SHP-2 catalytic activity, identifying a previously unrecognized behavior for this class of missense PTPN11 mutations. (+info)PTPN11 (Shp2) mutations in LEOPARD syndrome have dominant negative, not activating, effects. (5/34)
Multiple lentigines/LEOPARD syndrome (LS) is a rare, autosomal dominant disorder characterized by Lentigines, Electrocardiogram abnormalities, Ocular hypertelorism, Pulmonic valvular stenosis, Abnormalities of genitalia, Retardation of growth, and Deafness. Like the more common Noonan syndrome (NS), LS is caused by germ line missense mutations in PTPN11, encoding the protein-tyrosine phosphatase Shp2. Enzymologic, structural, cell biological, and mouse genetic studies indicate that NS is caused by gain-of-function PTPN11 mutations. Because NS and LS share several features, LS has been viewed as an NS variant. We examined a panel of LS mutants, including the two most common alleles. Surprisingly, we found that in marked contrast to NS, LS mutants are catalytically defective and act as dominant negative mutations that interfere with growth factor/Erk-mitogen-activated protein kinase-mediated signaling. Molecular modeling and biochemical studies suggest that LS mutations contort the Shp2 catalytic domain and result in open, inactive forms of Shp2. Our results establish that the pathogenesis of LS and NS is distinct and suggest that these disorders should be distinguished by mutational analysis rather than clinical presentation. (+info)Reduced phosphatase activity of SHP-2 in LEOPARD syndrome: consequences for PI3K binding on Gab1. (6/34)
LEOPARD (LS) and Noonan (NS) are overlapping syndromes associated with distinct mutations of SHP-2. Whereas NS mutations enhance SHP-2 catalytic activity, we show that the activity of three representative LS mutants is undetectable when assayed using a standard protein tyrosine phosphatase (PTP) substrate. A different assay using a specific SHP-2 substrate confirms their decreased PTP activity, but also reveals a significant activity of the T468M mutant. In transfected cells stimulated with epidermal growth factor, the least active LS mutants promote Gab1/PI3K binding, validating our in vitro data. LS mutants thus display a reduced PTP activity both in vitro and in transfected cells. (+info)Noonan syndrome and related disorders: dysregulated RAS-mitogen activated protein kinase signal transduction. (7/34)
Noonan syndrome is a relatively common, genetically heterogeneous Mendelian trait with a pleiomorphic phenotype. Prior to the period covered in this review, missense mutations in PTPN11 had been found to account for nearly 50% of Noonan syndrome cases. That gene encodes SHP-2, a protein tyrosine kinase that plays diverse roles in signal transduction including signaling via the RAS-mitogen activated protein kinase (MAPK) pathway. Noonan syndrome-associated PTPN11 mutations are gain-of-function, with most disrupting SHP-2's activation-inactivation mechanism. Here, we review recent information that has elucidated further the types and effects of PTPN11 defects in Noonan syndrome and compare them to the related, but specific, missense PTPN11 mutations causing other diseases including LEOPARD syndrome and leukemias. These new data derive from biochemical and cell biological studies as well as animal modeling with fruit flies and chick embryos. The discovery of KRAS missense mutation as a minor cause of Noonan syndrome and the pathogenetic mechanisms of those mutants is discussed. Finally, the elucidation of gene defects underlying two phenotypically related disorders, Costello and cardio-facio-cutaneous syndromes is also reviewed. As these genes also encode proteins relevant for RAS-MAPK signal transduction, all of the syndromes discussed in this article now can be understood to constitute a class of disorders caused by dysregulated RAS-MAPK signaling. (+info)Noonan syndrome and related disorders: alterations in growth and puberty. (8/34)
Noonan syndrome is a relatively common multiple malformation syndrome with characteristic facies, short stature and congenital heart disease, most commonly pulmonary stenosis (Noonan, Clin Pediatr, 33:548-555, 1994). Recently, a mutation in the PTPN11 gene (Tartaglia, Mehler, Goldberg, Zampino, Brunner, Kremer et al., Nat Genet, 29:465-468, 2001) was found to be present in about 50% of individuals with Noonan syndrome. The phenotype noted in Noonan syndrome is also found in a number of other syndromes which include LEOPARD (Gorlin, Anderson, Blaw, Am J Dis Child, 17:652-662, 1969), Cardio-facio-cutaneous syndrome (Reynolds, Neri, Hermann, Blumberg, Coldwell, Miles et al., Am J Med Genet, 28:413-427, 1986) and Costello syndrome (Hennekam, Am J Med Genet, 117C(1):42-48, 2003). All three of these syndromes share similar cardiac defects and all have postnatal short stature. Very recently, HRAS mutations (Aoki, Niihori, Kawame, Kurosawa, Ohashi, Tanaka et al., Nat Genet, 37:1038-1040, 2005) have been found in the Costello syndrome and germline mutations in KRAS and BRAF genes (Rodriguez-Viciana, Tetsu, Tidyman, Estep, Conger, Santa Cruz et al., Nat Genet, 2006; Niihori, Aoki, Narumi, Neri, Cave, Verloes et al., Nat Genet, 38:294-296, 2006) in the Cardio-facio-cutaneous syndrome. Phenotypic overlap between these genetic disorders can now be explained since each is caused by germline mutations that are major components of the RAS-MAPK pathway. This pathway plays an important role in growth factor and cytokine signaling as well as cancer pathogenesis. (+info)LEOPARD syndrome is a rare genetic disorder that is characterized by multiple lentigines (freckle-like spots), electrocardiographic abnormalities, ocular hypertelorism (wide-set eyes), pulmonic stenosis (narrowing of the pulmonary valve opening), abnormal genitalia, retardation of growth, and deafness. It is caused by mutations in the PTPN11 gene, which provides instructions for making a protein called SHP-2. This protein plays important roles in signaling pathways that control various cellular functions, such as cell growth and division. The signs and symptoms of LEOPARD syndrome can vary widely among affected individuals, even among members of the same family. Treatment is typically focused on managing the specific features of the condition in each individual.
Noonan Syndrome is a genetic disorder that affects various parts of the body and is characterized by distinctive facial features, short stature, heart defects, and developmental delays. It is caused by mutations in genes responsible for regulating cell growth and division. The syndrome is often identified at birth or in early childhood due to its physical manifestations, which may include widely spaced eyes, low-set ears, a short neck, a broad or webbed neck, chest deformities, and pulmonary valve stenosis. Noonan Syndrome affects both sexes and all races equally, with an estimated prevalence of 1 in 1,000 to 1 in 2,500 live births.
Neurofibromatoses are a group of genetic disorders that primarily affect the nervous system. The term "neurofibromatosis" is often used to refer to two specific conditions: neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2). These conditions are characterized by the growth of tumors on the nerves, called neurofibromas.
Neurofibromatosis type 1 (NF1): This is the most common form of neurofibromatosis, affecting about 1 in every 3,000 people worldwide. NF1 is caused by mutations in the NF1 gene and is characterized by the development of benign tumors on the nerves called neurofibromas. These tumors can develop anywhere on the body, including the skin, spinal cord, and brain. Other common features of NF1 include:
* Freckles in the underarms and groin area
* Lisch nodules (small, noncancerous growths) on the iris of the eye
* Bone abnormalities, such as scoliosis or bowing of the legs
* Learning disabilities or cognitive impairment
Neurofibromatosis type 2 (NF2): This form of neurofibromatosis is much rarer than NF1, affecting about 1 in every 30,000 people worldwide. NF2 is caused by mutations in the NF2 gene and is characterized by the development of benign tumors on the nerves that transmit sound from the inner ear to the brain (acoustic neuromas). These tumors can cause hearing loss, ringing in the ears, and balance problems. Other common features of NF2 include:
* Multiple schwannomas (tumors that develop on the protective covering of the nerves)
* Meningiomas (tumors that develop in the membranes surrounding the brain and spinal cord)
* Skin tumors called neurofibromas, although these are less common than in NF1
It is important to note that while neurofibromatoses can cause a range of symptoms and complications, most people with these conditions have a normal lifespan. With proper medical care and monitoring, it is possible to manage the symptoms and reduce the risk of complications.
Protein Tyrosine Phosphatase, Non-Receptor Type 11 (PTPN11) is a gene that encodes for the protein tyrosine phosphatase SHP-2. This enzyme regulates various cellular processes, including cell growth, differentiation, and migration, by controlling the balance of phosphorylation and dephosphorylation of proteins involved in signal transduction pathways. Mutations in PTPN11 have been associated with several human diseases, most notably Noonan syndrome and its related disorders, as well as certain types of leukemia.
A lentigo is a small, sharply defined, pigmented macule (flat spot) on the skin. It's usually tan, brown, or black and can appear on various parts of the body, particularly where the skin has been exposed to the sun. Lentigos are typically harmless and don't require treatment unless they're uncomfortable or for cosmetic reasons. However, some types of lentigines, such as lentigo maligna, can progress into melanoma, a type of skin cancer, so regular self-examinations and professional skin checks are important.
It is essential to differentiate between simple lentigos and lentigo maligna, which is a precancerous lesion. Lentigo maligna tends to occur in older individuals, often on the face, and can appear as a large, irregularly shaped, and darkly pigmented patch. A dermatologist should evaluate any suspicious or changing skin spots for proper diagnosis and treatment.
Pulmonary subvalvular stenosis is a rare cardiac condition that refers to the narrowing or obstruction of the pulmonary valve or the outflow tract below it, within the right ventricle of the heart. This results in restricted blood flow from the right ventricle to the pulmonary artery and subsequently to the lungs.
The narrowing can be caused by various factors such as a membranous shelf-like structure (dysplasia), a fibrous ring, or a tunnel-like narrowing of the outflow tract (tunneling). The severity of the stenosis may vary from mild to severe, and symptoms can range from shortness of breath, fatigue, and chest pain to more serious complications like heart failure or arrhythmias.
Diagnosis typically involves imaging tests such as echocardiography, cardiac MRI, or cardiac catheterization. Treatment options depend on the severity of the stenosis and may include monitoring, medications, or invasive procedures such as balloon dilation or surgical repair.
"Panthera" is not a medical term, but a biological genus name that includes large cats such as lions, tigers, leopards, jaguars, and snow leopards. It's a part of the taxonomic classification system used in biology to categorize and name organisms. Medical terminology typically relates to human health, disease processes, treatments, and anatomy.
Felidae is the biological family that includes all extant (living) members of the cat group, also known as felids. This family consists of big cats such as lions, tigers, and leopards, as well as small cats like domestic cats, cheetahs, and pumas. Felidae is part of the order Carnivora and is characterized by specialized adaptations for hunting and stalking prey, including retractile claws, sharp teeth, and flexible bodies. The family has a worldwide distribution, with species found in various habitats across all continents except Antarctica.
A syndrome, in medical terms, is a set of symptoms that collectively indicate or characterize a disease, disorder, or underlying pathological process. It's essentially a collection of signs and/or symptoms that frequently occur together and can suggest a particular cause or condition, even though the exact physiological mechanisms might not be fully understood.
For example, Down syndrome is characterized by specific physical features, cognitive delays, and other developmental issues resulting from an extra copy of chromosome 21. Similarly, metabolic syndromes like diabetes mellitus type 2 involve a group of risk factors such as obesity, high blood pressure, high blood sugar, and abnormal cholesterol or triglyceride levels that collectively increase the risk of heart disease, stroke, and diabetes.
It's important to note that a syndrome is not a specific diagnosis; rather, it's a pattern of symptoms that can help guide further diagnostic evaluation and management.
Carnivora is an order of mammals that consists of animals whose primary diet consists of flesh. The term "Carnivora" comes from the Latin words "caro", meaning flesh, and "vorare", meaning to devour. This order includes a wide variety of species, ranging from large predators such as lions, tigers, and bears, to smaller animals such as weasels, otters, and raccoons.
While members of the Carnivora order are often referred to as "carnivores," it is important to note that not all members exclusively eat meat. Some species, such as raccoons and bears, have an omnivorous diet that includes both plants and animals. Additionally, some species within this order have evolved specialized adaptations for their specific diets, such as the elongated canines and carnassial teeth of felids (cats) and canids (dogs), which are adapted for tearing and shearing meat.
Overall, the medical definition of Carnivora refers to an order of mammals that have a diet primarily consisting of flesh, although not all members exclusively eat meat.
An encyclopedia is a comprehensive reference work containing articles on various topics, usually arranged in alphabetical order. In the context of medicine, a medical encyclopedia is a collection of articles that provide information about a wide range of medical topics, including diseases and conditions, treatments, tests, procedures, and anatomy and physiology. Medical encyclopedias may be published in print or electronic formats and are often used as a starting point for researching medical topics. They can provide reliable and accurate information on medical subjects, making them useful resources for healthcare professionals, students, and patients alike. Some well-known examples of medical encyclopedias include the Merck Manual and the Stedman's Medical Dictionary.
Hutchinson's melanotic freckle, also known as Hutchinson's melanotic macule or naevus, is a type of pigmented lesion that can be a precursor to malignant melanoma, a serious form of skin cancer. It is typically characterized by the presence of darkly pigmented, irregularly shaped patches on the skin, often found on the face or neck.
The lesions are usually brown or black in color and may have an uneven border or surface. They can vary in size from a few millimeters to several centimeters in diameter. Hutchinson's melanotic freckles are typically larger, darker, and more irregularly shaped than common freckles.
These lesions are named after Sir Jonathan Hutchinson, an English surgeon and pathologist who first described them in the late 19th century. It is important to note that while Hutchinson's melanotic freckles can be a sign of increased risk for developing melanoma, not all such lesions will become cancerous. However, any changes in size, shape, or color of these lesions should be evaluated by a healthcare professional as soon as possible.
Underlying Noonan syndrome1
- Different mechanisms of disease have been demonstrated to be associated with the two classes of PTPN11 mutations underlying Noonan syndrome and Noonan syndrome with multiple lentigines (also known as LEOPARD syndrome). (biomedcentral.com)
Noonan and LEOPARD3
- Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. (ny.gov)
- P0-related protein (PZR), a Noonan and Leopard syndrome target, is a member of the transmembrane Immunoglobulin superfamily. (ox.ac.uk)
- PZR promotes cell migration on the extracellular matrix (ECM) molecule, fibronectin, by interacting with SHP-2 (Src homology-2 domain-containing protein tyrosine phosphatase-2), a molecule essential for skeletal development and often mutated in Noonan and Leopard syndrome patients sharing overlapping musculoskeletal abnormalities and cardiac defects. (ox.ac.uk)
PTPN1121
- LEOPARD syndrome, also known as Noonan syndrome with multiple lentigines, is a rare autosomal dominant disorder most often caused by missense mutations in the PTPN11 gene, which encodes the protein tyrosine phosphatase SHP2. (medscape.com)
- [ 4 ] Molecular studies have proven that LEOPARD syndrome and Noonan syndrome are allelic disorders caused by different missense mutations in PTPN11, a gene encoding the protein tyrosine phosphatase SHP-2 located at band 12q24.1. (medscape.com)
- In 2005, Ogata and Yoshida documented that PTPN11 mutations can be identified in approximately 40% of Noonan syndrome patients and in greater than 80% of LEOPARD syndrome patients. (medscape.com)
- [ 11 ] They revealed that whereas Noonan syndrome is caused by gain-of-function PTPN11 mutations, LEOPARD syndrome mutants are catalytically defective and act as dominant negative mutations that interfere with growth factor/Erk-mitogen-activated protein kinase-mediated signaling. (medscape.com)
- LEOPARD syndrome may be caused by heterozygous missense mutation of Tyr 279 Cys in the PTPN11 gene. (medscape.com)
- In 2006, Tartaglia et al reported that germline mutations in the PTPN11 gene cause LEOPARD and Noonan syndromes, whereas somatic mutations in the same gene contribute to leukemogenesis. (medscape.com)
- Reported in 2005, Kalidas et al performed mutation screening and linkage analysis of PTPN11 in 3 families, each of which had a history of LEOPARD syndrome for 3 generations. (medscape.com)
- No variations in sequence were observed in the other 2 families, and negative lod scores excluded linkage to the PTPN11 locus, showing that LEOPARD syndrome is genetically heterogeneous. (medscape.com)
- Writzl et al reported a family with molecularly proven (p.Thr468Met in PTPN11) LEOPARD syndrome in a father and his adult son. (medscape.com)
- Mutations in the PTPN11 (non-receptor protein tyrosine phosphatase type 11) gene are responsible for virtually all cases of LEOPARD syndrome and about half of the Noonan syndrome cases, notes Kontaridis. (scienceblog.com)
- By creating an LS mouse model that reproduced features of the human disorder, the Kontaridis group found that the mutations in PTPN11 that cause LEOPARD syndrome are distinct, and lead to a loss of phosphatase activity and hyperactivation of the AKT/mTOR pathway - which leads to the development of hypertrophic cardiomyopathy. (scienceblog.com)
- Noonan syndrome with multiple lentigines (NSML) which is part of a group called Ras/MAPK pathway syndromes, is a rare autosomal dominant, multisystem disease caused by a mutation in the protein tyrosine phosphatase, non-receptor type 11 gene (PTPN11). (wikipedia.org)
- More than 90 mutations causing Noonan syndrome have been identified in the PTPN11 gene. (nih.gov)
- Mutations in PTPN11 cause Noonan syndrome (NS), a developmental disorder characterized by facial dysmorphisms, short stature, skeletal and haematological defects, and cardiovascular abnormalities. (lu.se)
- PTPN11 mutations also occur in several human cancers, including juvenile myelomonocytic leukaemia (JMML), myelodysplastic syndrome (MDS), B-cell acute lymphoblastic leukaemia (BLL), and acute myelogeneous leukaemia (AML). (lu.se)
- PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity. (lu.se)
- Spectrum of mutations in PTPN11 and genotype-phenotype correlation in 96 patients with Noonan syndrome and five patients with cardio-facio-cutaneous syndrome. (lu.se)
- PTPN11 mutations are the only genetic abnormalities reported so far in some patients with NL/MGCLS and in one individual with LEOPARD syndrome and MGCL. (unifesp.br)
- PTPN11 mutations are also found in LEOPARD syndrome (LS), an allelic variant of NS. (uni-goettingen.de)
- PTPN11-Mutationen können auch bei der allelische Variante von NS, dem LEOPARD-Syndrom (LS) gefunden werden. (uni-goettingen.de)
- LEOPARD SYNDROME, a disorder that has clinical features overlapping those of Noonan Syndrome, is also due to mutations in PTPN11. (jefferson.edu)
Congenital7
- Now a new study showing that the mTOR inhibitor drug rapamycin can reverse cardiac muscle damage in a mouse model of the congenital disease LEOPARD syndrome not only identifies the first possible medical treatment for this rare condition, but also demonstrates the importance of targeted therapies in managing congenital diseases. (scienceblog.com)
- Kontaridis's lab investigates LEOPARD syndrome and Noonan syndrome, two of a cluster of congenital diseases known as "RASopathies," which are the result of defects caused by mutations in genes in the RAS signaling pathway. (scienceblog.com)
- Our findings in LEOPARD syndrome may additionally provide the first glimpse of a much broader implication - a potential mechanism for the treatment of other, more common congenital hypertrophy disorders. (scienceblog.com)
- PVS has been seen in the setting of well-defined congenital syndromes, most notably Holt-Oram syndrome, Noonan syndrome, and Leopard syndrome. (medscape.com)
- While pulmonic valvular stenosis is primarily a congenital malformation, it may also occur as part of congenital rubella syndrome. (medscape.com)
- Noonan syndrome (NS) is characterized by characteristic facies, short stature, congenital heart defect, and developmental delay of variable degree. (nih.gov)
- INTRODUCTION AND OBJECTIVES: Molecular characterization of congenital heart diseases now includes the not infrequent dysmorphic Noonan syndrome. (bvsalud.org)
Abnormalities5
- Moynahan first documented the association of the syndrome with cardiac abnormalities and short stature in 1962. (medscape.com)
- LEOPARD syndrome affects approximately 200 individuals worldwide and is clinically distinguished by multiple lentigines (freckle-like spots on the skin), as well as craniofacial defects, deafness, and blood abnormalities which can give rise to pediatric leukemias. (scienceblog.com)
- Additional dermatologic abnormalities (axillary freckling, localized hypopigmentation, interdigital webbing, hyperelastic skin) Mild mental retardation is observed in about 30% of those affected by the syndrome Nystagmus (involuntary eye movements), seizures, or hyposmia (reduced ability to smell) has been documented in a few patients In 2004, a patient was reported with recurrent upper extremity aneurysms that required surgical repairs. (wikipedia.org)
- It encompasses several syndromes with overlapping abnormalities including the DIGEORGE SYNDROME, VELOCARDIOFACIAL SYNDROME, and CONOTRUNCAL AMOMALY FACE SYNDROME. (harvard.edu)
- Abnormalities in gray matter microstructure in young adults with 22q11.2 deletion syndrome. (harvard.edu)
Cardiofaciocutaneous3
- The term RASopathies includes disorders with mutations in the genes that code for the proteins of the RAS/MAPK pathway, such as neurofibromatosis type 1, Noonan syndrome, Legius syndrome, LEOPARD syndrome, Costello syndrome, and cardiofaciocutaneous syndrome. (medscape.com)
- Epilepsy is a major clinical issue in cardiofaciocutaneous (CFC) syndrome when it is caused by the BRAF gene. (noonansyndrome.org.uk)
- OBJECTIVES: To describe 11 patients with cardiofaciocutaneous syndrome (CFC) and compare them with 130 patients with other RAS-MAPK syndromes (111 Noonan syndrome patients [NS] and 19 patients with LEOPARD syndrome). (bvsalud.org)
Short stature3
- Noonan syndrome with multiple lentigines (NSML) is a condition in which the cardinal features consist of lentigines, hypertrophic cardiomyopathy, short stature, pectus deformity, and dysmorphic facial features including widely spaced eyes and ptosis. (nih.gov)
- Noonan Syndrome (NS) [OMIM 163950] is an autosomal dominant disorder characterized by short stature, facial dismorphism, webbed neck, heart defects (most commonly pulmonic stenosis and hypertrophic cardiomyopathy), cryptorchism and hematological anomalies. (uni-goettingen.de)
- Short stature, developmental delay, language difficulties and ectodermal anomalies were more frequent in CFC patients when compared with other neuro-cardio-faciocutaneous syndromes (P (bvsalud.org)
Disorders4
- Syndromes are diseases, conditions, or disorders that involve a particular group of signs and symptoms. (kidshealth.org)
- Although differential diagnosis between these two syndromes could be difficult, particularly in the first age of life, we underline the relevance in discriminating these two disorders in terms of affected signaling pathway to allow an effective targeted pharmacological treatment. (biomedcentral.com)
- In this manuscript, the authors described the mutation spectrum causally linked to Noonan syndrome (NS) (MIM PS163950) and clinically related disorders, and the associated clinical outcome, based on a pediatric cohort of 47 affected subjects. (biomedcentral.com)
- Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFCS) are related developmental disorders caused by mutations in genes encoding various components of the RAS-MAPK signaling cascade. (unifesp.br)
Costello12
- Transitional cell cancer of the bladder was reported in a 11-year-old boy [9] and a 14-year-old girl[10] with Costello syndrome. (familialcancerdatabase.nl)
- Suri and Garret[11] observed a vestibular schwannoma and cataract (both of which can be found in NF2) in a 33 year old patient with Costello syndrome. (familialcancerdatabase.nl)
- Gripp reviewed the occurrence of cancer in Costello syndrome: the most common tumor in CS is rhabdomyosarcoma (RMS), followed by neuroblastoma and bladder carcinoma[12]. (familialcancerdatabase.nl)
- Philip N, Sigaudy S. Costello syndrome. (familialcancerdatabase.nl)
- Delineation of the Costello syndrome. (familialcancerdatabase.nl)
- Feingold M. Costello syndrome and rhabdomyosarcoma. (familialcancerdatabase.nl)
- Franceschini P, Licata D, Di Cara G, Guala A, Bianchi M, Ingrosso G, Franceschini D. Bladder carcinoma in Costello syndrome: report on a patient born to consanguineous parents and review. (familialcancerdatabase.nl)
- Second case of bladder carcinoma in a patient with Costello syndrome. (familialcancerdatabase.nl)
- Suri M, Garrett C. Costello syndrome with acoustic neuroma and cataract. (familialcancerdatabase.nl)
- Tumor predisposition in Costello syndrome. (familialcancerdatabase.nl)
- HRAS and the Costello syndrome. (familialcancerdatabase.nl)
- Campus R, Di Rocco M, Sementa AR, Senes FM, Magillo P, Dodero P. [Gastric fibroid polyp in a 4-month-old girl with Costello syndrome]. (familialcancerdatabase.nl)
RAF11
- More than 25 mutations causing Noonan syndrome have been identified in the RAF1 gene. (nih.gov)
Known as LEOPARD syndrome2
- Noonan syndrome with multiple lentigines was formerly known as LEOPARD syndrome. (medlineplus.gov)
- Consistent with their distinctive consequences on SHP2 function and signal transduction, these mutations do not cause NS but underlie Noonan syndrome with multiple lentigines (NSML), previously known as LEOPARD syndrome (MIM PS151100), a disorder similar but distinct from NS. (biomedcentral.com)
Hypertrophic1
- A related study in today's on-line issue of the JCI, by a team of scientists at the University Health Network, Toronto, found that in a mouse model of Noonan syndrome, excessive activity of an enzyme called ERK (a downstream target of the RAS pathway) led to the development of hypertrophic cardiomyopathy, and that treatment with an ERK inhibitor currently being tested as an anti-cancer agent, reversed the cardiomyopathy. (scienceblog.com)
Disorder4
- LEOPARD syndrome is a complex dysmorphogenetic disorder of variable penetrance and expressivity. (medscape.com)
- Noonan syndrome with multiple lentigines (NSML) is a rare inherited disorder. (medlineplus.gov)
- Buzz has a very rare genetic disorder called Leopard Syndrome which has resulted in him being an intensive care patient six times since he w. (theairambulanceservice.org.uk)
- Leopard sydrome (LS), a clinically related disorder, is caused by mutations in the SHP-2 catalytic domain. (lu.se)
NSML1
- NSML is similar to Noonan syndrome . (medlineplus.gov)
Clinical3
- Our next step will be to test rapamycin in a clinical trial to evaluate the effect of this treatment in humans with LEOPARD syndrome. (scienceblog.com)
- Expert consensus document: Clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement. (nih.gov)
- Typical craniofacial dysmorphisms are present and there is clinical and molecular overlap with CFC syndrome[1-5]. (familialcancerdatabase.nl)
Molecular1
- Categorización de alteraciones genéticas en niveles predictivos de terapias objetivo estándar, de investigación o hipotéticas en los informes de patología molecular. (igenomix.com)
Diseases2
- Due to the rarity of the syndrome itself, it is hard to determine whether certain additional diseases are actually part of the syndrome. (wikipedia.org)
- Due to the large surgical volume at Mayo Clinic, and the availability of detailed medical records, it is possible to evaluate anesthetic and surgical outcomes of a relatively large number of patients with extremely rare diseases such as myotonia congenita, cor triatriatum, DiGeorge syndrome, LEOPARD syndrome, Swyer-James syndrome and the like. (mayo.edu)
Myelomonocytic1
- [ 14 ] To date, 2 patients with LEOPARD syndrome and myelomonocytic or acute lymphoblastic leukemias have been reported. (medscape.com)
Defects1
- Noonan syndrome is linked to defects in several genes. (nih.gov)
Allelic1
- Consequently, LEOPARD syndrome [LS] and Noonan syndrome have traditionally been thought to be allelic variants with the same disease etiology. (scienceblog.com)
Mutants1
- In 2006, Hanna et al found that Noonan syndrome mutations enhance SHP-2 catalytic activity, whereas the activity of representative LS mutants is undetectable when assayed using a standard PTP substrate. (medscape.com)
Phenotype2
- Bleeding Severity and Phenotype in 22q11.2 Deletion Syndrome-A Cross-Sectional Investigation. (harvard.edu)
- The phenotype bears similarities to that of TURNER SYNDROME that occurs only in females and has its basis in a 45, X karyotype abnormality. (jefferson.edu)
Malformations1
- 3, 4, 5] Eisenmenger syndrome associated with trisomy 13 also results in RVOTO in conjunction with other cardiac malformations. (medscape.com)
Genes2
- La identificación de pacientes con riesgo de susceptibilidad hereditaria al cáncer depende de la capacidad de caracterizar genes y alteraciones asociadas con un mayor riesgo de cáncer, así como de recopilar antecedentes personales y familiares detallados que ayuden a identificar el modo de herencia, así como a otros miembros de la familia en riesgo de sufrir esta susceptibilidad. (igenomix.com)
- El panel de precisión de cáncer de pulmón de Igenomix proporciona un análisis completo de los genes más comunes responsables del desarrollo de un crecimiento maligno en las vías respiratorias o el tejido pulmonar mediante secuenciación de próxima generación (NGS) para comprender completamente el espectro de genes de predisposición al cáncer de pulmón relevantes. (igenomix.com)
Mutation1
- Noonan syndrome with multiple lentigines is caused by a different missense mutation of the same gene. (wikipedia.org)
19691
- An alternative name of the condition, LEOPARD syndrome, is a mnemonic, originally coined in 1969, as the condition is characterized by some of the following seven conditions, the first letters of which spell LEOPARD, along with the characteristic "freckling" of the skin, caused by the lentigines that is reminiscent of the large cat. (wikipedia.org)
Characteristic1
- While uncommon, it is the typical morphology characteristic of Noonan syndrome. (medscape.com)
Cardiac1
- Cardiac transplantation in children with Noonan syndrome. (jefferson.edu)
Inheritance1
- The inheritance rate is low, although when part of Noonan syndrome it is autosomal dominant. (medscape.com)
Distinct1
- Type V is considered as a distinct entity as, unlike the other types, is usually associated with both cystic renal disease and liver fibrosis (Caroli syndrome). (biomedcentral.com)
Multiple2
- Multiple lentigines on the face of a child with LEOPARD syndrome. (medscape.com)
- Noonan syndrome with multiple lentigines (formerly called LEOPARD syndrome ) is a condition that affects many areas of the body. (nih.gov)