Disease genetic noonan syndrome. Medical search. Frequent questions

Not all individuals with Noonan syndrome with multiple lentigines have all the characteristic features of this condition. (medlineplus.gov)
The remaining individuals with Noonan syndrome with multiple lentigines do not have an identified mutation in any of these four genes. (medlineplus.gov)
Approximately 25% of individuals with Noonan syndrome have mental retardation . (medscape.com)
The final adult height of individuals with Noonan syndrome is about 161-167 cm in males and 150-155 cm in females, which approaches the lower limit of normal. (wikipedia.org)
Identification of attention problems and other psychiatric comorbidities will be an important element in developing appropriate educational and treatment goals to benefit individuals with Noonan syndrome" (Pierpont et al. (bartleby.com)
Gene mutations identified in individuals with Noonan Syndrome phenotype are involved in the R AS /MAPK (mitogen-activated protein kinase) signal transduction pathway , also known as R AS opathy. (igenomix.net)

Noonan syndrome with multiple lentigines is one of a group of related conditions collectively known as RASopathies. (medlineplus.gov)
In addition to Noonan syndrome with multiple lentigines, the RASopathies include Noonan syndrome, cardiofaciocutaneous syndrome , Costello syndrome , neurofibromatosis type 1 , and Legius syndrome . (medlineplus.gov)
NS belongs to a family of genetic syndromes known as "RASopathies," which refers to the fact that all these conditions are caused by mutations in a common cellular signaling pathway (known as the RAS-MAPK signaling pathway). (sagepub.com)
Many different genes are known to be associated with Noonan syndrome and other RASopathies. (thermofisher.com)
Using Ion AmpliSeq Designer , they created a fully customized panel targeting 86 genes known to be implicated in Noonan syndrome and other RASopathies. (thermofisher.com)
Ion AmpliSeq On-Demand panels provide over 5,000 genes known to be associated with various inherited diseases, including the RASopathies. (thermofisher.com)
Knowledge about the genetic causes of RASopathies is constantly evolving due to the efforts of clinical researchers like those at IPATIMUP. (thermofisher.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)
NS is part of a group of diseases termed RASopathies that are caused by activating mutations of proteins belonging to the Ras and mitogen-activated protein kinase families. (noonan.no)
The EURAS consortium brings together patients and researchers to combine patient-reported data with cutting-edge technologies for the development of effective disease management strategies for neurodevelopmental RASopathies. (euras-project.eu)
Erlangen, 18 July 2023 - RASopathies are a group of genetic diseases that arise from increased signalling down the cellular transduction pathway known as RAS, which plays a crucial role in multiple developmental processes. (euras-project.eu)
V., the project aims to gain a deeper understanding of the underlying disease mechanisms, create a framework for improved diagnosis, and develop effective treatments for neurodevelopmental RASopathies. (euras-project.eu)
The patient report-based registry, designed by a team of clinicians, bioinformaticians and patient representatives specifically for neurodevelopmental RASopathies, will allow for the stratification of patient cohorts, assessment of disease progression, and evaluation of treatment effectiveness. (euras-project.eu)
Noonan syndrome (NS) belongs to a group of genetic disorders called RASopathies that are caused by germ-line mutations that affect genes residing along the canonical RAS-MAPKinase signaling pathway. (armi.org.au)
RASopathies are a group of genetic syndromes that may be as common as 1:1000. (globalgenes.org)
The syndromes RASopathies Network focuses on include: cardio-facio-cutaneous (CFC), Costello (CS), LEOPARD/NSML, Neurofibromatosis type 1 (NF1), and Noonan (NS). (globalgenes.org)
Molecular Genetics of Noonan Syndrome and RASopathies. (igenomix.net)
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)

Several other genes that have been linked to a Noonan syndrome-like phenotype have been recognized as well but have been found in a very small number of persons. (medscape.com)
Thus, studying an inherited human cancer syndrome with hiPSCs illuminated early oncogenesis prior to the accumulation of secondary genomic alterations, enabling us to discover microRNA dysregulation, establishing a genotype-phenotype association for JMML and providing therapeutic targets. (health-innovations.org)
A rare genetic polymalformative syndrome characterized by a Noonan-like phenotype associated with increased risk of developing juvenile myelomonocytic leukemia (JMML). (globalgenes.org)
The Noonan-like (NS) phenotype includes dysmorphic facial features (i.e. high forehead hypertelorism downslanting palpebral fissures ptosis low-set ears prominent philtrum and short neck with or without pterygium colli) developmental delay hypotonia and small head circumference. (globalgenes.org)
2010). The face of Noonan syndrome: Does phenotype predict genotype. (igenomix.net)
Several additional genes associated with a Noonan syndrome-like phenotype in fewer than ten individuals have been identified. (nih.gov)
In this case report, we describe a patient who met the cardinal triad and also presented additional clinical data that have not been previously reported, which contribute to broadening the disease phenotype. (bvsalud.org)
Objective: To analyze the clinical phenotype and screen the genetic mutations of hereditary deafness in three deaf families to clarify their molecular biology etiology. (bvsalud.org)

This slow growth results in affected individuals being shorter than average, although less than half of people with Noonan syndrome with multiple lentigines have significantly short stature. (medlineplus.gov)
Abstract Noonan syndrome is an inherited disorder of cell growth affecting both males and females and characterized by distinctive facial features, short stature, heart defects, bleeding problems, chest wall abnormalities, and other signs and symptoms. (bartleby.com)
Noonan syndrome (NS) is a genetic condition with multiple associated characteristics including short stature, congenital heart disease, distinctive facial features, skeletal anomalies, and developmental delays. (sagepub.com)
Noonan syndrome can impact many areas of the body and is typically characterized by distinct facial features, short stature, congenital heart defects, developmental delay, and other comorbid conditions. (thermofisher.com)
Moynahan first documented the association of the syndrome with cardiac abnormalities and short stature in 1962. (medscape.com)
Noonan syndrome (NS) is characterized by characteristic facies, short stature, congenital heart defect, and developmental delay of variable degree. (nih.gov)
Myhre syndrome (MS) is a rare autosomal-dominant disorder characterized by short stature, intellectual disability, skeletal anomalies, restricted joint mobility, distinctive facial dysmorphism, and deafness. (e-apem.org)
She had a healthy brother, and there was no family history of short stature, mental retardation, or genetic disorders. (e-apem.org)
Noonan syndrome often involves short stature, distinctive facial features, congenital heart defects and bleeding problems. (emoryhealthsciblog.com)
The case describes complications of NS, a genetic disease that causes multiple malformations, short stature and heart disease, with less frequent digestive disorders, PMDN and cryptorchidism, except when the BRAF gene is altered. (sbni2023.com.br)
Bloom syndrome is a rare genetic disorder characterized by short stature , a sun-sensitive rash, and impaired intellectual development. (fastlyheal.com)
FDA indications in children include GH deficiency (GHD), Turner syndrome, idiopathic short stature, small for gestational age with failure to attain normal growth percentiles, Prader-Willi syndrome (PWS), chronic renal insufficiency, Noonan syndrome, and short stature due to short stature homeobox gene haploinsufficiency. (ajmc.com)
2 Other relatively rare conditions that also affect growth in children are Turner syndrome (TS), small for gestational age (SGA) (with failure to attain the lower portion of the normal growth curve by age 2), Prader-Willi syndrome (PWS), chronic renal insufficiency (CRI), Noonan syndrome, and short stature due to short stature homeobox (SHOX) gene haploinsufficiency ( Table 1 ). (ajmc.com)

Cancer in Noonan, Costello, cardiofaciocutaneous and LEOPARD syndromes. (medscape.com)
The signs and symptoms of cardiofaciocutaneous syndrome overlap significantly with those of two other genetic conditions, Costello syndrome and Noonan syndrome . (medlineplus.gov)
Unlike Costello syndrome, which significantly increases a person's cancer risk, cancer does not appear to be a major feature of cardiofaciocutaneous syndrome. (medlineplus.gov)
In these cases, affected individuals may actually have Costello syndrome or Noonan syndrome, which are also caused by variants in genes involved in RAS/MAPK signaling. (medlineplus.gov)
Some of the diseases belonging to this category include Noonan syndrome, Costello syndrome, Neurofibromatosis type 1, c ardio - facio - cutaneous syndrome and others. (igenomix.net)

As the condition name suggests, Noonan syndrome with multiple lentigines is very similar to a condition called Noonan syndrome, and it can be difficult to tell the two disorders apart in early childhood. (medlineplus.gov)
Treatment is focused on the symptoms of Noonan syndrome and may include cardiac therapy, growth hormone therapy, physical and speech therapy, ophthalmologic treatment, management of bleeding disorders, treatment of lymphatic problems, and urologic therapy (in males). (medscape.com)
Other musculoskeletal manifestations in Noonan syndrome are associated with undifferentiated connective-tissue disorders which can be associated with joint contractures (tightness) or joint hypermobility (looseness). (wikipedia.org)
Multiple genetic studies overwhelmingly point out for the role of LZTR1 in a wide range of human disorders, such as Noonan Syndrome (a genetic disease), liver cancer, childhood cancer, and Schwannoma, a benign tumor that affects nerves. (news-medical.net)
RASopathy disorders are a group of genetic syndromes caused by mutations in the Ras/mitogen-activated protein (MAPK) pathway. (thermofisher.com)
One of the most common RASopathy disorders is Noonan syndrome, which is present in about 1 in 1,000 to 2,500 live births. (thermofisher.com)
Sometimes the syndrome can be identified based on presentation alone, but it is recommended to use genetic testing to eliminate other disorders that share similar characteristics. (thermofisher.com)
Noonan syndrome is a genetic disease that is associated with developmental disorders. (mbexc.de)
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)
Determining the genetic causes of inherited heart diseases provides valuable insight for molecular confirmation of clinical diagnosis, differential diagnosis of related disorders, and risk assessment of family members. (asperbio.com)
A deep-learning algorithm is helping doctors and researchers to pinpoint a range of rare genetic disorders by analysing pictures of people's faces. (thebrighterside.news)
Powered by the GestaltMatcher algorithm, the Face2Gene app analyzes a face to suggest genetic disorders a person might have. (thebrighterside.news)
So the Face2Gene app is currently available for free to healthcare professionals, many of whom use the system as a kind of second opinion for diagnosing rarely seen genetic disorders, says study co-author Karen Gripp, a medical geneticist at the Nemours/Alfred I. duPont Hospital for Children in Wilmington, Delaware. (thebrighterside.news)
I will discuss how we can leverage our hPSC-based platform to study cardiogenesis and cardiac function in genetic disorders as a unique opportunity to discover the molecular perturbations responsible for CHDs or cardiomyopathies. (armi.org.au)
Causes of male infertility - UpToDate Causes of male infertility Endocrine and systemic disorders (hypogonadotropic hypogonadism) Congenital disorders Congenital GnRH deficiency (Kallmann syndrome) Iron overload syndromes Multiorgan genetic disorders (Prader-Willi syndrome, Laurence-Moon-Biedl syndrome, familial cerebellar ataxia) Low sperm count (oligospermia) A malfunctioning immune system. (ubbcluj.ro)
[ 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)
If we want to understand how the brain creates memories, and how genetic disorders distort the brain's machinery, then the fragile X gene is an ideal place to start. (emoryhealthsciblog.com)
What are genetic disorders? (fastlyheal.com)
Most genetic disorders are caused by a mutation in a single gene. (fastlyheal.com)
There are many different types of genetic disorders, but some of the more common ones include cystic fibrosis, sickle cell anemia, and Tay-Sachs disease. (fastlyheal.com)
There are a number of other genetic disorders that can cause similar problems, and many of them are much rarer than Down syndrome. (fastlyheal.com)
There are several different types of genetic disorders, but they all have one thing in common: they are caused by an error in the genetic code. (fastlyheal.com)
Angelman syndrome is a rare genetic disorder characterized by severe intellectual and developmental disability, sleep disorders, and problems with movement and balance. (fastlyheal.com)
What are the causes of genetic disorders? (fastlyheal.com)
There are many possible causes of genetic disorders, including problems with the way a cell functions, changes in the structure of a gene, or an abnormality in the number of chromosomes. (fastlyheal.com)
What are the symptoms of genetic disorders? (fastlyheal.com)
There are a variety of symptoms that can be associated with genetic disorders. (fastlyheal.com)
How are genetic disorders identified? (fastlyheal.com)
There are a number of ways that genetic disorders can be identified. (fastlyheal.com)
It ranks third place among child development disorders in front of congenital malformations and Down's syndrome 21 . (bvsalud.org)

Noonan syndrome with multiple lentigines (formerly called LEOPARD syndrome) is a condition that affects many areas of the body. (medlineplus.gov)
The lentigines seen in Noonan syndrome with multiple lentigines typically first appear in mid-childhood, mostly on the face, neck, and upper body. (medlineplus.gov)
Up to 20 percent of people with Noonan syndrome with multiple lentigines who have heart problems have a narrowing of the artery from the heart to the lungs (pulmonary stenosis). (medlineplus.gov)
People with Noonan syndrome with multiple lentigines can have a distinctive facial appearance. (medlineplus.gov)
At birth, people with Noonan syndrome with multiple lentigines are typically of normal weight and height, but in some, growth slows over time. (medlineplus.gov)
Variants (also known as mutations) in one of several genes can cause Noonan syndrome with multiple lentigines. (medlineplus.gov)
A study by Cessans et al comparing growth patterns in patients with Noonan syndrome based on genotype found that at birth, patients with PTPN11 mutations tended to be shorter and thinner than were those with mutations in SOS1 , KRAS , or Noonan syndrome with multiple lentigines-associated PTPN11 (NSML- PTPN11 ). (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)
Multiple lentigines on the face of a child with LEOPARD syndrome. (medscape.com)
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)
Based on clinical manifestations and genetic test results, proband 1 was diagnosed with multiple lentigines Noonan syndrome, and probands 2 and 3 were diagnosed with Noonan syndrome. (bvsalud.org)

Noonan Syndrome is a dominant gene pattern. (bartleby.com)
In his quest to discover what causes congenital heart disease, Bruce D. Gelb, MD , has developed an extensive program in genomics and gene investigation, focusing on traits associated with heart malformations. (mssm.edu)
Standard genetic analysis methods involving single-gene tests are often utilized by inherited disease researchers but these methods alone may be time consuming and expensive to uncover the many variants involved in complex diseases such as Noonan syndrome. (thermofisher.com)
This gene catalog is available for both the Ion Genestudio S5 and Genexus platforms by either searching for gene(s) of interest, or through using the Disease Research Areas (DRA) found on Ion AmpliSeq Designer. (thermofisher.com)
Scientists at the Heart Center of the University Medical Center Göttingen have for the first time found an approach for a personalised therapy option with "gene editing" for the Noonan Syndrome. (mbexc.de)
Scientists at the Heart Center of the University Medical Center Göttingen (UMG) and the Cluster of Excellence "Multiscale Bioimaging" (MBExC) have for the first time been able to identify the link between the underlying gene mutations and the development of heart muscle thickening (heart hypertrophy) for the congenital heart disease Noonan Syndrome. (mbexc.de)
Some people with the signs and symptoms of cardiofaciocutaneous syndrome do not have an identified variant in the BRAF , MAP2K1 , MAP2K2 , or KRAS gene. (medlineplus.gov)
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)
Previous studies show that inherited changes in the DNA code for the gene PTPN11 cause Noonan syndrome, a genetic disease that comes with a high risk for the blood cancer , JMML. (health-innovations.org)
Genetic heart conditions assembled in this testing menu are detectable mainly by multi-gene panels , but yet single gene testing and targeted mutation analysis are also available. (asperbio.com)
Gripp had read case reports describing premature dental growth in children with Wiedemann-Steiner syndrome, an exceedingly rare disorder caused by mutations in a gene called KMT2A. (thebrighterside.news)
My Faulty Gene is a nonprofit organization which provides information and assistance to any individual whose family medical history suggests genetic testing might be helpful in identifying an increased risk of disease due to a genetic mutation. (globalgenes.org)
Background Genetic causes of male infertility are hypothesized to involve multiple types of mutations, from single gene defects to complex chromosome rearrangements. (ubbcluj.ro)
The discussion of male infertility focuses on genetic factors impairing spermatogenesis and includes numerical chromosomal anomalies such as Klinefelter syndrome, structural chromosomal anomalies such as Y-chromosome microdeletions, certain single gene mutations, syndromic diseases, and epigenetic mutations. (ubbcluj.ro)
Either at genomic or at proteomic level, mutations have significant impact on normal gene or protein function, and human diseases could be associated with mutations like nonsynonymous single-nucleotide variations (nsSNVs) on amino acids. (hindawi.com)
Although data of both gene mutations and PTMs are increasing fast, the proteome-wide analysis on the relationship between damaged PTMs and human diseases is not well studied. (hindawi.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)
Conclusion: Missense mutations in the PTPN11 gene may be the cause of the disease in the three deaf families. (bvsalud.org)
In this study, we sought to explore the wide spectrum of genetic heterogeneity associated with hearing loss in Japan, and to discover novel candidate genes associated with hearing loss, using trio analysis of probands and their parents, and four originally developed gene groups ranked by priority (tiers), as a new strategy to filter candidate variants. (biomedcentral.com)
When he was 20 months old, macrocrania, malnutrition, poor eye contact and global hypotonia were reported and, 2 months later, he was diagnosed with Noonan Syndrome (NS), with a BRAF gene variant of zero frequency. (sbni2023.com.br)
(PATUA SYNDROME) (also known as Oculo-auricula-vertebral spectrum) is a genetic disease caused by dystrophic dystrophin (DABN) gene defect which affects several parts of the body, including the eye, ear, spinal cord, and muscles. (fastlyheal.com)

The most common signs leading to the diagnosis of Noonan syndrome are unique facial characteristics and musculoskeletal features. (wikipedia.org)
first diagnosis of Noonan syndrome was in 1883 by means of Kobylinski. (bartleby.com)
Noonan syndrome: clinical features, diagnosis, and management guidelines. (medscape.com)
The genetic and molecular confirmation for an accurate clinical diagnosis of a symptomatic patient. (igenomix.net)
But equally important is that families are supported through their diagnostic journey, or in some cases their diagnostic odyssey , to a diagnosis and beyond by other patients and their families with the same rare genetic syndrome. (fdna.health)
This Australian based support group works closely with medical professionals to improve the diagnosis rate while reducing the rate of misdiagnosis for Noonan syndrome families. (fdna.health)
They support both medical professionals and families in coming to a Noonan syndrome diagnosis and managing the care of those affected with the syndrome. (fdna.health)
Connecting patients and their families with the tools and support to ensure they receive a faster, more accurate genetic analysis and diagnosis is essential in improving the outcomes for individuals with a rare disease. (fdna.health)
Booking a session with a genetic counselor will be incredibly beneficial in supporting you and your loved ones in fully understanding the diagnosis and targeting pathways for treatment. (fdna.health)
2} Differential diagnosis include Ellis-van Creveld syndrome, Acropectoral syndrome, Greig-cephalopolysyndactyly syndrome, Saldino-Noonan syndrome, Acrocallosal syndrome. (pediatriconcall.com)
Diagnosis of short rib polydactyly syndrome type IV (Beemer-Langer syndrome) with cystic hygroma: A case report. (pediatriconcall.com)
It is important to get an early diagnosis for Down syndrome so you can get the proper care for your child . (fastlyheal.com)

They also taught the model to classify different genetic forms of a third disorder known as Noonan syndrome. (thebrighterside.news)

The facial characteristics are most prominent in infancy, becoming less apparent with age in many people with Noonan syndrome. (wikipedia.org)
In the eyes, hypertelorism (widely set eyes) is a defining characteristic, present in 95% of people with Noonan syndrome. (wikipedia.org)

With the exception of lentigines, Noonan syndrome patients exhibit nearly identical features and pathologies. (scienceblog.com)
[ 1 ] Zeisler and Becker first described the syndrome in 1936 in a 24-year-old woman with progressive generalized lentigines, hypertelorism, pectus carinatum, and prognathism. (medscape.com)

Skin signs and symptoms in Noonan syndrome include lymphedema (lymph swelling of the extremities), keloid formation, excessive scar formation, hyperkeratosis (overdevelopment of outer skin layer), pigmented nevi (darkly pigmented skin spots), and connective tissue disease. (wikipedia.org)
webbing is one of the main symptoms of Noonan syndrome. (bartleby.com)
The lysosomal accumulation of glycosaminoglycans is responsible for the widespread signs and symptoms found in this disease. (arizona.edu)
In most cases, they are limited to attenuate the symptoms of the disease. (mbexc.de)
The altered signaling interferes with the development of many organs and tissues, leading to the signs and symptoms of cardiofaciocutaneous syndrome. (medlineplus.gov)
These conditions, with Neurofibromatosis 1 (NF1) and Noonan syndrome (NS) being the most common, can manifest with a wide range of symptoms, including specific facial features, heart defects, skin changes and varying degrees of neurological and neurocognitive impairment. (euras-project.eu)
However, there is currently no disease-specific therapy for the neurocognitive symptoms, which imposes a permanent high burden on the patients, mostly children, and their families. (euras-project.eu)
This UK-based support group was founded in 1982 and aims to further research and treatment into rare genetic syndromes and their symptoms. (fdna.health)
The symptoms of congenital heart disease can range from mild to life-threatening , and the severity of the condition can vary from person to person. (fastlyheal.com)
2) Pregnant women with recent possible Zika virus exposure and symptoms † of Zika virus disease should be tested to diagnose the cause of their symptoms . (cdc.gov)

Cancer risk in patients with Noonan syndrome carrying a PTPN11 mutation. (medscape.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 has also been shown to be caused by mutations in KRAS and PTPN11 genes [5] . (bionity.com)
They go on to conclude that by starting with skin cells of JMML patients with inherited PTPN11 mutations, they were able to create JMML cells with only these mutations, screening out the 'genetic noise' that can obscure disease mechanisms. (health-innovations.org)
Germline PTPN11 defects cause Noonan syndrome (NS), and specific inherited mutations cause NS/JMML. (health-innovations.org)
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)
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)
Clonal duplication of a germline PTPN11 mutation due to acquired uniparental disomy in acute lymphoblastic leukemia blasts from a patient with Noonan syndrome. (lu.se)
Early fetal death associated with compound heterozygosity for Noonan syndrome-causative PTPN11 mutations. (lu.se)
Acquisition of JAK2, PTPN11, and RAS mutations during disease progression in primary myelodysplastic syndrome. (lu.se)
The mutational spectrum of PTPN11 in juvenile myelomonocytic leukemia and Noonan syndrome/myeloproliferative disease. (lu.se)

Overview Noonan syndrome is a disorder caused by a genetic mutation that causes various parts of the patient's body to develop abnormally. (bartleby.com)
Noonan Syndrome is an autosomal dominant disorder, which is inherited by the mutation from one affected parent. (bartleby.com)
CONCLUSION@#Genetic testing has a great clinical significance for the prevention and reduction of congenital hearing loss, but the scope needs to be updated and redefined by removing mutation sites with a very low rate, adding new significant sites, and improvement of the technical strategies. (bvsalud.org)
We found that a disease-associated mutation, which disturbs the niches where blood stem cell development occurs, can lead to leukemia formation. (emoryhealthsciblog.com)
Characterization of a new disease-causing mutation of SH2D1A in a family with X-linked lymphoproliferative disease. (lu.se)
Many individuals who have been diagnosed with viral cardiomyopathies probably have a genetic risk factor, which even may be a classic mutation that is brought out by the environment. (medscape.com)

Abnormalities in the limbs and extremities may occur in Noonan syndrome. (wikipedia.org)
There are several different abnormalities caused by Noonan Syndrome that can affect people. (bartleby.com)
[9] Approximately 40-50% of fetuses diagnosed with AVCD have Down syndrome, and a further 15-20% are associated with other chromosomal abnormalities and syndromes, such as DiGeorge syndrome . (wikipedia.org)
Skin abnormalities occur in almost everyone with cardiofaciocutaneous syndrome. (medlineplus.gov)
Known to cause heart abnormalities, characteristic facial features, and for some children mild intellectual disability, Noonan syndrome causes a growth deficiency. (theasianparent.com)
Despite this, many genetic causes of male infertility remain unknown, even though it is recognised that rates of genetic abnormalities are likely to be increased among men requiring ART. (ubbcluj.ro)
Detection of certain genetic causes of male infertility allows couples to be informed about the potential to transmit genetic abnormalities that may affect the health of offspring. (ubbcluj.ro)

Heart defects occur in most people with cardiofaciocutaneous syndrome. (medlineplus.gov)
Cardiofaciocutaneous syndrome is also characterized by distinctive facial features. (medlineplus.gov)
Infants with cardiofaciocutaneous syndrome typically have weak muscle tone (hypotonia), feeding difficulties, and a failure to grow and gain weight at the normal rate (failure to thrive). (medlineplus.gov)
Cardiofaciocutaneous syndrome is a very rare condition whose incidence is unknown. (medlineplus.gov)
Cardiofaciocutaneous syndrome can be caused by variants (also known as mutations) in several genes. (medlineplus.gov)
Variants in any of these genes can result in the characteristic features of cardiofaciocutaneous syndrome. (medlineplus.gov)

Noonan Syndrome (autosomal dominant condition) is a fairly common disease, affecting 1 in every 1,000-2,500 people. (bartleby.com)

Noonan syndrome (NS) is a genetic disorder that may present with mildly unusual facial features, short height, congenital heart disease, bleeding problems, and skeletal malformations. (wikipedia.org)
A type of neurocutaneous syndrome that can cause tumors to grow inside the brain, spinal cord, organs, skin, and skeletal bones. (hopkinsmedicine.org)

Bleeding diathesis is present in as many as half of all patients with Noonan syndrome. (medscape.com)
Noonan syndrome was first recognized as a unique entity in 1963, when Noonan and Ehmke described a series of patients with unusual facies and multiple malformations, including congenital heart disease. (medscape.com)
These patients were previously thought to have a form of Turner syndrome , with which Noonan syndrome shares numerous clinical features. (medscape.com)
The observation that patients with Noonan syndrome have normal karyotypes was important in allowing the distinction to be made between the Turner and Noonan syndromes. (medscape.com)
The primary source of morbidity and mortality in patients with Noonan syndrome depends on the presence and type of congenital heart disease. (medscape.com)
A study by Jongmans et al also demonstrated an elevated cancer risk in patients with Noonan syndrome. (medscape.com)
Growth patterns of patients with Noonan syndrome: correlation with age and genotype. (medscape.com)
This type of congenital heart defect is associated with patients with Down syndrome (trisomy 21) or heterotaxy syndromes . (wikipedia.org)
[3] The pattern seen in those patients with Noonan syndrome differ from those patients who have Down syndrome in that "partial" AVCD is more prevalent in those with NS, whereas those with down syndrome show a prevalence of the "complete" form of AVCD. (wikipedia.org)
Two patients underwent ICD for primary prevention, and one underwent PPI for distal AV conduction disease. (bvsalud.org)
BOSTON - Congenital heart diseases affect approximately one in 100 patients, making them the most common type of birth defect and the number-one cause of pediatric deaths. (scienceblog.com)
While our numbers are still very limited, we report the first patients in whom we were not only able to stabilize, but to reverse the disease of the heart. (noonan.no)
To better understand diseases with a genetic component, a popular approach is to take skin cells from patients with a disease and use enzymes to coax the cells back along the differentiation pathway to become induced pluripotent stem cells or iPSCs. (health-innovations.org)
V. The patient organisation will coordinate the recruitment for the planned European Patient Registry that welcomes CFC, CS, and SYNGAP1 patients, as well as patients with Noonan Syndrome. (euras-project.eu)
In 2004, the Yale-New Haven Adult Congenital Heart Program was initiated as the first integrated program in the State of Connecticut dedicated to the care of adult patients with complex congenital heart disease. (yale.edu)
The mission of the LGDA is to bring hope to and improve the quality of life of patients diagnosed with generalized lymphatic anomaly (GLA), kaposiform lymphangiomatosis (KLA), Gorham-Stout disease (GSD) and central conducting lymphatic anomaly (CCLA) through support networks, education, research and advocacy. (globalgenes.org)
His main research focus is intravascular interventions for patients with congenital heart disease. (societyforpediatricresearch.org)
Many of them are also involved in advocacy work for rare disease patients within the public sphere and strive to create more awareness about specific rare genetic syndromes and the individuals affected by them. (fdna.health)
This organization engages in advocacy, research, and support for Down syndrome patients and their families. (fdna.health)
It provides both day to day support for patients and their families, as well as more long term education, research, and advocacy for the syndrome. (fdna.health)
Support groups and genetic counselors worldwide are offering crucial and critical services for families, and the public, as they advocate for the needs of rare disease patients. (fdna.health)
[ 14 ] To date, 2 patients with LEOPARD syndrome and myelomonocytic or acute lymphoblastic leukemias have been reported. (medscape.com)
Importantly, however, not all patients with LEOPARD syndrome demonstrate linkage to 12q24.1. (medscape.com)
The neighbor cell effect could be frustrating efforts to treat leukemias in patients with Noonan syndrome and a related condition, juvenile myelomonocytic leukemia (JMML). (emoryhealthsciblog.com)
Given the variety of complications that NS causes to patients, this syndrome should undergo further analysis by the scientific community, since there are few studies about it. (sbni2023.com.br)
Missense mutations in SH2D1A identified in patients with X-linked lymphoproliferative disease differentially affect the expression and function of SAP. (lu.se)
Rapid detection of intracellular SH2D1A protein in cytotoxic lymphocytes from patients with X-linked lymphoproliferative disease and their family members. (lu.se)
[ 3 ] In Western countries, the financial burden on patients ranges from $300 to $1,300 per patient year, increasing with more severe disease. (medscape.com)
more than half of all expenditures are attributed to the 10-20% of patients with the most severe disease. (medscape.com)
Although early reports described IE exclusively in children whose hearts were structurally abnormal because of congenital heart disease or acquired rheumatic heart disease, this infection has more recently been reported in diverse groups of patients. (cdc.gov)

This includes turner syndrome, down syndrome, and achondroplasia. (avtoradio.tj)
Turner syndrome is when having too many, too few, or disrupted chromosomes results in health. (avtoradio.tj)
Turner syndrome is a very rare chromosomal disorder that affects a person's sex chromosomes. (fastlyheal.com)
Turner syndrome is caused by missing or extra pieces of DNA on a person's sex chromosomes. (fastlyheal.com)
Turner syndrome is often an inherited disorder. (fastlyheal.com)

Abnormal features of Noonan syndrome at the age of 3 months: Note the eyebrow slant and left-side eyelid dropping. (handwiki.org)
Abnormal features of Noonan syndrome at the age of 3 months: Note the low-set, posteriorly rotated, and abnormally formed ear. (handwiki.org)
A genetic disorder that causes abnormal development of many parts and systems of the body. (hopkinsmedicine.org)
Males with Klinefelter's syndrome have an extra X chromosome, which causes abnormal development of the testicles. (ubbcluj.ro)
Achondroplasia (a condition that causes abnormal growth of cartilage resulting in dwarfism) · down syndrome · noonan syndrome (a. (avtoradio.tj)

For many congenital heart diseases, such as Noonan Syndrome, the link between the genetic changes (mutations) and the heart malformations have not yet been fully understood. (mbexc.de)

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)
Consequently, LEOPARD syndrome [LS] and Noonan syndrome have traditionally been thought to be allelic variants with the same disease etiology. (scienceblog.com)
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)
LEOPARD syndrome is a complex dysmorphogenetic disorder of variable penetrance and expressivity. (medscape.com)

The development of the ears and auditory system may be affected in people with Noonan's syndrome. (wikipedia.org)
Noonan's syndrome. (hopkinsmedicine.org)
It's a side effect of Noonan's syndrome, making everyday tasks, like walking and sitting, difficult. (theasianparent.com)

Rett syndrome is a neuro-developmental disorder that affects about one in every 10,000 girls worldwide. (fastlyheal.com)

Hypertrophic cardiomyopathy (HCM) is defined by the presence of increased ventricular wall thickness or mass in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality. (nih.gov)
It is a very rare syndrome characterised by short ribs, various gastrointestinal, cranial structural abnormality, post-axial polydactyly, cystic renal disease, heart and laterality disorder, ambiguous genitalia. (pediatriconcall.com)
A genetic disorder is caused by an abnormality in an individual's genome. (fastlyheal.com)

His lab uses human iPSCs, cardiac directed differentiation, genome editing (CRISPR), multi-omics, 3D organoids and engineered heart tissues as developmental and disease models. (armi.org.au)
Noonan syndrome-14 (NS14) is a recessive developmental disorder within the RASopathy clinical spectrum. (nih.gov)
Down syndrome is the most common genetic disorder , and it can lead to a variety of health and developmental problems. (fastlyheal.com)

The birth prevalence of Noonan syndrome (NS) is estimated between 1:1000 to 1:2500. (orpha.net)
Cherubism is currently listed in Orphanet as a rare disease of unknown prevalence due to its wide clinical spectrum, with approximately 300 cases reported in various ethnic groups worldwide. (sajr.org.za)
CDC has updated the interim guidance for U.S. health care providers caring for pregnant women with possible Zika virus exposure in response to 1) declining prevalence of Zika virus disease in the World Health Organization's Region of the Americas (Americas) and 2) emerging evidence indicating prolonged detection of Zika virus immunoglobulin M (IgM) antibodies. (cdc.gov)
As the prevalence of Zika virus disease declines, the likelihood of false-positive test results increases. (cdc.gov)

Therefore it is thought that dysregulation of this pathway during development is responsible for many of the clinical features of this syndrome [6] . (bionity.com)

Stessman, H.A., Bernier, R. & Eichler, E.E. A genotype-first approach to defining the subtypes of a complex disease. (nature.com)

The pathophysiology of Noonan syndrome is not fully understood but is associated with mutations in genes that are part of the RAS/RAF/MEK/ERK signal transduction pathway, an important regulator of cell growth. (medscape.com)

Pyloric stenosis and cardiac valve disease may respond to surgery. (arizona.edu)
The genetic mutations that alter the signaling pathways involved in cardiac development have been implicated in approximately 30 percent of the defects associated with congenital heart diseases," explains the study's senior author Maria Kontaridis, PhD, a scientist in the Division of Cardiovascular Medicine at BIDMC and Assistant Professor of Medicine at Harvard Medical School. (scienceblog.com)
Our cardiothoracic surgical team has extensive expertise in congenital heart disease and adult cardiac surgery with an experience that spans three decades. (yale.edu)
Dr. Badheka's primary research interest to examine, analyze and evaluate outcomes data for various critical diseases including uncommon cardiac conditions. (societyforpediatricresearch.org)

The condition was named after American pediatric cardiologist Jacqueline Noonan, who described her first case in 1963. (wikipedia.org)
Introduction Noonan syndrome, named eponymously for the pediatric cardiologist who ﬁrst described it, is an autosomal dominant disorder (Gelb and Tartaglia, 2006). (bartleby.com)
[2] The condition was first described in 1883 and was named after American pediatric cardiologist Jacqueline Noonan, who described further cases in 1963. (handwiki.org)

umg/ mbexc) Congenital heart diseases are the most common organ defects. (mbexc.de)
The mission of the HGF is to achieve better health outcomes for heart diseases and related chronic health conditions in our communities and enhance the quality of life through health education, care support, and connection to community resources. (globalgenes.org)

Molecular genetic testing, however, can aid in confirmation. (medscape.com)
Researchers at the Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) has been developing targeted NGS assays to further clinical research into Noonan syndrome. (thermofisher.com)
Using the heart muscle cells obtained in this way, the molecular and functional features of the disease could be investigated in greater detail. (mbexc.de)
The cause of the overactivation of the RAS-MAP kinase signaling pathway, the pathological enlargement of the cells and the changes in the excitation-contraction coupling of the heart could be explained and a molecular signature of the disease could be constructed. (mbexc.de)
Additionally, it provides us with a unique opportunity to access large patient cohorts, which is especially challenging for rare diseases but essential for achieving the project's clinical objectives," states Prof. Anna Fejtova, Professor of Molecular Psychiatry at the Universitätsklinikum Erlangen and scientific coordinator of EURAS. (euras-project.eu)

[ 6 ] Juvenile myelomonocytic leukemia and myeloproliferative disorder have also been associated with Noonan syndrome. (medscape.com)
The clinical spectrum of NS may differ slightly between causative genes, and some forms have been described as ''Noonan like'' (NS-like disorder with juvenile myelomonocytic leukemia and NS-like disorder with loose anagen hair). (orpha.net)
Newly diagnosed with Noonan syndrome-like disorder with juvenile myelomonocytic leukemia? (globalgenes.org)

The Y chromosome contains the genetic material with the codes that determine the male gender, and related masculine characteristics and development. (ubbcluj.ro)
If a person has physical characteristics associated with a genetic disorder, they may be diagnosed with the disorder. (fastlyheal.com)

A genetic disorder characterized by the growth of numerous cysts filled with fluid in the kidneys. (hopkinsmedicine.org)
Because of the role MEK plays in signaling heart growth, Gregor Andelfinger believes studies with a larger number of participants are now required to evaluate long-term side effects, optimal dosing and optimal treatment windows as well as investigate this treatment for other types of heart disease. (noonan.no)
Growth disorders noonan syndrome - a rare genetic disorder that affects about 1 in 1,000-2,500 children, both boys and girls. (avtoradio.tj)
X-linked lymphoproliferative disease associated with hypogammaglobulinemia and growth-hormone deficiency. (lu.se)

Noonan syndrome is a type of RASopathy, the underlying mechanism for which involves attenuation of the RAS/MAPK cell signaling pathway. (wikipedia.org)

Infants with Noonan syndrome can be difficult to recognize by facial appearance alone. (medscape.com)
Researchers at FDNA, a digital-health company in Boston, Massachusetts, first trained the artificial intelligence (AI) system to distinguish Cornelia de Lange syndrome and Angelman syndrome - two conditions with distinct facial features - from other similar conditions. (thebrighterside.news)
Charles Schwartz, a geneticist at the Greenwood Genetic Center in Greenwood, South Carolina, distributed facial pictures of ten children with "fairly recognizable" syndromes and asked attendees to come up with the correct diagnoses. (thebrighterside.news)

Enzyme replacement therapy with galsulfase (Naglazyme®) is beneficial in alleviating some of the manifestations of this disease. (arizona.edu)
Specifically, Dr. Akchurin focuses on the role of iron metabolism alterations in hematologic and non-hematologic manifestations and complications of chronic kidney disease in children, including effects of iron in kidney fibrosis. (societyforpediatricresearch.org)

Eventually, FDNA wants to develop this technology to help other companies filter, prioritize and interpret genetic variants of unknown significance during DNA analysis. (thebrighterside.news)
Whole exome sequencing (WES), involves sequencing of coding exons comprising approximately 2% of the whole human genome, which are estimated to contain approximately 85% of pathogenic variants associated with monogenic disease [ 6 ]. (biomedcentral.com)

Mental retardation can be seen in approximately 25% of individuals affected by Noonan syndrome. (igenomix.net)

The findings described in this report suggest that a life-threatening form of heart disease affecting young infants might be treatable, which, if true, would be unprecedented and so meaningful for the families whose lives this devastating problem touches,» commented Dr. Bruce Gelb, director of the Mindich Child Health and Development Institute at the Icahn School of Medicine at Mount Sinai, in New York City. (noonan.no)
Data findings show that 'gain of function' genetic changes that happen to increase this protein's expression were enough to cause leukemia-related changes in cells. (health-innovations.org)
The group state that these findings provide a toe-hold in efforts to design specific treatments for this form of the disease. (health-innovations.org)

[3] [10] The remaining 30-40% of cases are not linked to a syndrome, with AVCD observed without other major defects. (wikipedia.org)
Among birth defects, congenital heart disease is the leading cause of infant mortality. (msdmanuals.com)

In this work, we chose eight experimentally demonstrated damaged PTMs to elucidate their association to human diseases including inherited diseases and cancers (somatic diseases). (hindawi.com)

Noonan Syndrome (NS) is a rare genetic syndrome typically evident at birth and often linked to early-onset severe heart disease. (noonan.no)
Noonan syndrome is genetic disorder so rare that only one in 1,000 - 5,000 children has it, and three-year-old Ellie Madigan is part of that tiny fraction of children. (theasianparent.com)
Our RARE Concierge Services Guides are available to assist you by providing information, resources and connections as you navigate your rare disease journey. (globalgenes.org)
Provide information, support and advocacy to families caring for a child with an undiagnosed or rare genetic condition. (globalgenes.org)
Lack of access to the right information about the possible genetic syndrome or rare disease the family faces. (fdna.health)
A professional will enrich one's understanding of certain rare genetic syndromes including Aarskog-Scott syndrome and others. (fdna.health)
Wildervanck syndrome (also known as cervico-oculo-acoustic dysplasia) is a very rare disease, characterized by the typical triad of cervical vertebral fusion or Klippel-Feil anomaly, Duane syndrome (paresis of the sixth cranial nerve), and hearing loss. (bvsalud.org)
Infective endocarditis (IE) is a rare but potentially life-threatening disease in children and has an incidence of 0.8-3.3 cases/1,000 pediatric hospital admissions ( 1 ). (cdc.gov)

It affects 1 in 1,000-2,500 live births with no sex predominance, and is the most common syndromal cause of congenital heart disease, except for Down's syndrome (Zaras, et al. (bartleby.com)
An arterial disease, cause unknown, that most often affects the medium and large arteries of young to middle-aged women. (hopkinsmedicine.org)

Some of the characteristic features of Noonan syndrome include a large head with excess skin on the back of the neck, low hairline at the nape of the neck, high hairline at the front of the head, triangular face shape, broad forehead, and a short, webbed neck. (wikipedia.org)

An expert in Noonan syndrome, Dr. Gelb has studied the genetic origins of this disease to understand its pathogenesis. (mssm.edu)
The ability to induce human induced pluripotent stem cells (hiPSCs) from terminally differentiated cells such as skin fibroblasts provides an opportunity to study disease pathogenesis, which has not been possible in the past with JMML. (health-innovations.org)
2007) provides an opportunity to study disease pathogenesis. (eprf.ca)

Testosterone deficiency syndrome. (clevelandclinic.org)

Noonan syndrome is the second most common syndromic cause of congenital heart disease. (wikipedia.org)
Clinical follow-up for NAA15 , KMT5B , and ASH1L highlighted new syndromic and nonsyndromic forms of disease. (nature.com)

The incidence of Noonan syndrome is estimated to be 1 case per 1000 to 1 case per 2500 live births. (medscape.com)

Noonan and related syndromes result from mutations in several genes that encode proteins that cells use to signal from the outer membrane to the nucleus. (mssm.edu)

like Noonan syndrome, all of these cancers are associated with RAS signaling pathway mutations. (medscape.com)
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)

Noonan Syndrome is a genetic disorder which a means it can be passed through parents to their children. (bartleby.com)
[8] 45% of children with Down syndrome have congenital heart disease. (wikipedia.org)
The laboratory performs diagnostic and interventional catheterization procedures in children and adults with congenital heart disease across the age spectrum. (yale.edu)
Her research focuses on the linkage and integration of large datasets and the application of econometric modeling to identify modifiable drivers of outcomes, value, and health inequities for children with congenital heart disease. (societyforpediatricresearch.org)
They also offer support for specific educational strategies to help Williams syndrome children in school. (fdna.health)
Children with noonan syndrome. (avtoradio.tj)
Children with Noonan syndrome are estimated to have a risk of developing leukemia or other cancers that is eight times higher than their peers. (emoryhealthsciblog.com)
Data from the Prevention of Allergy: Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle (PARSIFAL) Study and the Multidisciplinary Study to Identify the Genetic and Environmental Causes of Asthma in the European Community Advanced (GABRIELA) reinforce the concept of the hygiene hypothesis. (medscape.com)

Noonan Syndrome is a genetic disorder, it prevents normal development in different parts of the body (Mayo, 2016). (bartleby.com)

al-Gazali LI, Sztriha L, Dawodu A, Varady E, Bakir M, Khdir A, Johansen J. Complex consanguinity associated with short rib-polydactyly syndrome III and congenital infection-like syndrome: a diagnostic problem in dysmorphic syndromes. (pediatriconcall.com)

Anatomy1

Diseases18

Chemicals and Drugs5

Analytical, Diagnostic and Therapeutic Techniques and Equipment2

Phenomena and Processes4

Individuals with Noonan syndrome6

RASopathies18

Phenotype8

Short stature13

Costello5

Disorders30

Multiple lentigines11

Gene22

Diagnosis12

Known as Noonan syndrome1

People with Noonan syndrome2

Lentigines2

Symptoms10

PTPN1114

Mutation6

Abnormalities7

Cardiofaciocutaneous syndrome6

Autosomal dominant condition1

Skeletal2

Patients30

Turner5

Abnormal5

Malformations1

LEOPARD4

Noonan's3

Rett1

Abnormality3

Developmental3

Prevalence4

Clinical features1

Genotype1

Mutations in genes1

Cardiac4

Pediatric cardiologist3

Heart diseases2

Molecular5

Juvenile myelomon3

Characteristics2

Growth4

RASopathy1

Facial3

Manifestations2

Variants2

Mental retardation1

Findings3

Defects2

Somatic1

Rare8

Affects2

Characteristic1

Pathogenesis3

Deficiency1

Syndromic2

Live births1

Several genes1

Pathway2

Children8

20161

Dysmorphic1