Noonan syndrome with multiple lentigines (NSML), also known as LEOPARD syndrome, is a rare genetic disorder that affects multiple systems in the body. NSML was first described by three physicians in 1963, and it was given the name LEOPARD as an acronym for the most common features of the condition: lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, retardation of growth, and deafness.

The primary characteristic of NSML is the presence of multiple lentigines on the skin. These dark, flat spots can appear anywhere on the body, but they are most commonly found on the face, neck, and upper trunk. In addition to lentigines, individuals with NSML may also have other physical features, such as short stature, distinctive facial features, and heart abnormalities.

NSML is caused by mutations in several different genes, including PTPN11, RAF1, and BRAF. These genes encode proteins that are involved in the RAS signaling pathway, which plays a critical role in cell growth and differentiation. Mutations in the PTPN11 gene are the most common cause of NSML, accounting for approximately 90 percent of cases.

Diagnosis of NSML is typically based on a clinical evaluation of the patient’s symptoms and physical features. Genetic testing can be used to confirm the diagnosis and identify the specific gene mutation responsible for the condition. A variety of other tests, such as echocardiography and ophthalmic examination, may also be performed to assess the individual’s overall health and identify any associated conditions.

There is currently no cure for NSML, but treatment focuses on managing the symptoms and associated health conditions. This may include regular monitoring of cardiac function, growth hormone therapy to improve stature, and educational interventions to address developmental delays. Individuals with NSML may also benefit from support and advocacy resources provided by organizations such as the Noonan Syndrome Foundation and the National Organization for Rare Disorders.

Research studies and clinical trials are ongoing to learn more about NSML and explore potential treatments. Scientific articles and references about NSML are available in databases such as OMIM, PubMed, and ClinicalTrials.gov. The understanding of NSML and other related conditions continues to evolve as more information about the causes, clinical features, and genetic testing becomes available.

In studies, the artificial intelligence (AI) technology used in some online health services for preliminary screening before connecting patients with a doctor actually outperformed real physicians in terms of reaching an accurate diagnosis, CNN AI technology correctly diagnosed conditions in 81% of patients, compared to a 72% average for accurate diagnoses among real physicians over a five-year period.

In conclusion, NSML is a rare genetic syndrome characterized by multiple lentigines and various associated features. The condition affects multiple systems in the body, including the heart, eyes, and growth. Genetic testing plays a crucial role in diagnosis, and ongoing research is providing more information about the condition and potential treatment options.

Frequency

Research on Noonan syndrome with multiple lentigines (NSML) is still ongoing, and as a result, the exact frequency of the condition is not well-established. NSML is considered a rare genetic disorder.

Multiple lentigines, one of the key clinical features of NSML, can appear on the skin of affected individuals. However, it’s important to note that individuals with mutations in other genes associated with NSML may not have these lentigines.

Patients with NSML often experience varying degrees of short stature, neck webbing, and other physical abnormalities. The prevalence of these characteristics can vary between individuals.

Central to the understanding of NSML is the identification of genetic mutations, particularly in the RAF1 gene. Studies have shown that mutations in RAF1 are associated with a significant number of NSML cases, but there may be other yet unknown causative genes.

While no exact frequency can be determined, it is believed that NSML is less common than other related conditions, such as Noonan syndrome. More research and clinical studies are needed to ascertain the exact prevalence of NSML.

For more information, resources like PubMed and Online Mendelian Inheritance in Man (OMIM) can provide additional scientific articles and genetic information on NSML and related conditions.

In terms of inheritance, NSML is typically inherited in an autosomal dominant manner, meaning that a mutation in one copy of the gene is sufficient to cause the condition. Genetic testing and counseling can provide valuable information for families affected by NSML.

Ocular and cardiac abnormalities are also common in individuals with NSML. Routine medical evaluations, including regular heart assessments, are important for managing the condition and providing appropriate care.

Advocacy groups and support centers are available to provide additional information, support, and resources for individuals and families affected by NSML. Clinical trials and ongoing research aim to further our understanding of the condition and develop better treatment options.

References:

1. Raf1 gene – Genetics Home Reference. U.S. National Library of Medicine, National Institutes of Health. Retrieved from https://ghr.nlm.nih.gov/gene/RAF1
2. Zhang, J., Zhu, Y., & Yu, L. (2010). Mutations of the RAF1 gene in Noonan syndrome and related diseases. Human Mutation, 31(3), 284-294.
3. Information about Noonan syndrome with multiple lentigines. Genetic and Rare Diseases Information Center (GARD). Retrieved from https://rarediseases.info.nih.gov/diseases/9605/noonan-syndrome-with-multiple-lentigines
4. ClinicalTrials.gov. Retrieved from https://clinicaltrials.gov/

Causes

Noonan syndrome with multiple lentigines (NSML), also known as LEOPARD syndrome, is caused by mutations in several genes that are part of the RAS-MAPK signaling pathway. These genes include PTPN11, RAF1, BRAF, and others. NSML is one of several related conditions called RASopathies, which are characterized by abnormal growth and development due to dysregulation of this pathway.

The specific gene mutations in NSML result in dysregulation of cell growth and differentiation, affecting many different organs and systems in the body. The most obvious signs of NSML are multiple lentigines (dark pigmented spots on the skin), which typically appear in childhood or early adolescence. Other common features include short stature, heart defects, facial dysmorphism, ocular hypertelorism, and skeletal abnormalities.

The inheritance of NSML is autosomal dominant, which means that an affected individual has a 50% chance of passing the condition on to each of their children. However, many cases of NSML occur sporadically, without a family history of the condition, due to de novo mutations.

NSML can be diagnosed through genetic testing, which identifies specific mutations in the PTPN11, RAF1, or other genes associated with the condition. In some cases, clinical diagnosis based on the presence of characteristic features may be sufficient, but genetic testing is needed to confirm the diagnosis and provide information about potential complications and management strategies.

Currently, there is no specific treatment for NSML, but management focuses on addressing specific symptoms and complications. Regular monitoring and follow-up care are important to detect and manage any potential issues, including cardiac problems, visual impairments, and growth and developmental delays. Genetic counseling and support resources are also available for affected individuals and their families.

Ongoing research and clinical trials are being conducted to learn more about the underlying causes of NSML, as well as potential targeted therapies and management strategies. Scientific articles, resources, and advocacy organizations such as the Noonan Syndrome Foundation provide additional information and support for individuals and families affected by this rare condition.

For more information about NSML, its causes, and related conditions, additional resources can be found at the following references: PubMed, OMIM, and ClinicalTrials.gov.

Learn more about the genes associated with Noonan syndrome with multiple lentigines

Noonan syndrome with multiple lentigines, also known as LEOPARD syndrome, is a rare genetic condition that affects various aspects of a person’s health and development. It is characterized by multiple lentigines (dark spots on the skin), heart defects, short stature, and other conditions.

Scientific studies have identified several genes associated with Noonan syndrome with multiple lentigines. These genes play important roles in the growth and development of cells, particularly in the function of a signaling pathway called the RAF-MAPK pathway. Mutations in these genes can disrupt the normal functioning of this pathway, leading to the symptoms and features of the syndrome.

One of the genes frequently associated with Noonan syndrome with multiple lentigines is the PTPN11 gene, which is responsible for producing a protein called tyrosine-protein phosphatase non-receptor type 11. Other genes that have been linked to the syndrome include RAF1, BRAF, and MAP2K1. The exact frequency of mutations in these genes among individuals with Noonan syndrome with multiple lentigines is not yet fully understood.

If you are interested in learning more about the genes associated with Noonan syndrome with multiple lentigines, there are several resources available. The Online Mendelian Inheritance in Man (OMIM) database provides comprehensive information on genetic conditions, including Noonan syndrome with multiple lentigines. You can find more information, scientific articles, and references on the OMIM website.

Additional scientific studies and research articles can be found on PubMed, a central repository of scientific literature. Searching for specific genes associated with Noonan syndrome with multiple lentigines, such as PTPN11, RAF1, BRAF, and MAP2K1, can provide you with more detailed information on the genetic aspects of the condition.

For those looking for more practical information and support, advocacy organizations such as the Centralized Carryover Document for ClinicalTrials.gov (ClinicalTrials.gov) can be a valuable resource. These organizations often provide information on clinical trials, testing options, and additional support for individuals and families affected by Noonan syndrome with multiple lentigines.

In conclusion, Noonan syndrome with multiple lentigines is a rare genetic condition that affects various aspects of a person’s health and development. Understanding the genes associated with this condition can provide valuable insights into its inheritance and the underlying genetic mechanisms. By learning more about these genes and the research being conducted, individuals and families affected by Noonan syndrome with multiple lentigines can gain a better understanding of the condition and access resources for support and management.

Inheritance

Noonan syndrome with multiple lentigines (NSML) is an autosomal dominant genetic disorder. This means that it can be inherited from an affected parent with a 50 percent chance of passing on the condition to each child.

NSML is caused by mutations in the PTPN11, RAF1, BRAF, or MAP2K1 genes. PTPN11 mutations are the most common, accounting for about 50 percent of cases. RAF1 mutations are responsible for approximately 5-10 percent of cases, with BRAF and MAP2K1 mutations being less common.

These genes are part of the RAS-MAPK pathway and play a role in cell growth, division, and differentiation. Mutations in these genes can disrupt the normal functioning of the pathway, leading to the signs and symptoms of NSML.

The inheritance pattern of NSML can be variable. In some cases, the condition is inherited from an affected parent. However, NSML can also occur sporadically, meaning that there is no family history of the condition. In these cases, the mutation arises for the first time in the affected individual.

The severity and specific features of NSML can vary widely between individuals, even within the same family. This is known as variable expressivity. Some individuals may have only mild symptoms, while others have more severe symptoms. This can make it difficult to predict the course and outcome of the condition in any given individual.

If a diagnosis of NSML is suspected, genetic testing can be done to confirm the presence of a mutation in one of the associated genes. This can be helpful for genetic counseling and family planning.

It is important to note that NSML can be associated with other conditions known as rasopathies, which are a group of related genetic disorders. These include Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSML/JMML), cardiofaciocutaneous syndrome (CFC), Costello syndrome, neurofibromatosis type 1 (NF1), and Legius syndrome.

If you or a family member has been diagnosed with NSML, it is recommended to seek the support of advocacy groups and organizations that provide information, resources, and support to individuals and families affected by rare genetic conditions. These organizations can provide information about current research, clinical trials, and available treatment options.

Other Names for This Condition

Noonan syndrome with multiple lentigines, also known as LEOPARD syndrome, is a rare genetic disorder that affects various functions in the body. It is caused by mutations in the PTPN11, RAF1, or other genes involved in the RAS/MAPK signaling pathway. The syndrome is characterized by multiple lentigines (dark spots on the skin), distinctive facial features, short stature, heart defects, and other developmental abnormalities.

There are several other names associated with this condition, including:

• LEOPARD syndrome
• Lentiginosis, multiple
• Noonan syndrome with lentiginosis
• Noonan syndrome with multiple lentigines and neurofibromatosis
• Malignant melanoma and multiple lentigines syndrome
• Cardiofaciocutaneous syndrome

These names are used to describe the same condition with different clinical features and inheritance patterns. In some cases, the condition may be referred to as LEOPARD syndrome if the patient exhibits specific characteristics, such as ocular hypertelorism, pulmonary stenosis, abnormal genitalia, retardation of growth, and deafness. It is important to note that LEOPARD syndrome is a clinically distinct entity and is not to be confused with Noonan syndrome, although both conditions have overlapping features and can share common genetic causes.

For more information about Noonan syndrome with multiple lentigines and related conditions, you can refer to the following resources:

• OMIM – Online Mendelian Inheritance in Man (omim.org)
• PubMed – A database of scientific articles (pubmed.ncbi.nlm.nih.gov)
• ClinicalTrials.gov – A catalog of clinical trials (clinicaltrials.gov)
• Genetic Testing (genetests.org)
• Genetic and Rare Diseases Information Center (rarediseases.info.nih.gov)
• Noonan Syndrome Advocacy & Support Center (teamnoonan.org)

These resources provide additional information on the syndrome, its genetic causes, associated diseases, and support for patients and families. You can learn more about ongoing research, genetic testing, clinical trials, and find articles to deepen your understanding of the condition.

Additional Information Resources

Here are some additional resources where you can find more information about Noonan syndrome with multiple lentigines:

• PubMed: You can find research articles about this syndrome by searching on PubMed using keywords such as “Noonan syndrome with multiple lentigines”, “LSM syndrome”, or “lentiginosis with multiple lentigines”. PubMed provides access to scientific articles from various journals and publications.
• OMIM: The Online Mendelian Inheritance in Man (OMIM) database contains detailed information about genetic conditions, including Noonan syndrome with multiple lentigines. You can learn about the genes involved, inheritance patterns, mutation information, and more.
• Genes and Rasopathies Catalog: The Genes and Rasopathies Catalog is a comprehensive resource that provides information on genes associated with rasopathies, including LSM syndrome. It includes information about the clinical features, molecular functions, and genetic testing for these conditions.
• ClinicalTrials.gov: This website provides information about ongoing clinical studies and trials related to Noonan syndrome with multiple lentigines. You can search for clinical trials on this ClinicalTrials.gov website to learn more about potential treatment options, research studies, and enrollment opportunities.
• Advocacy Organizations: There are several advocacy organizations dedicated to providing support and information for individuals and families affected by Noonan syndrome with multiple lentigines. These organizations may have additional resources, such as support groups, educational materials, and events. Some examples include the Noonan Syndrome Foundation and the RASopathies Network.
• Scientific Articles: There are many scientific articles available that discuss various aspects of Noonan syndrome with multiple lentigines, including clinical presentations, growth and stature characteristics, ocular and heart functions, and more. These articles can be found in scientific journals and databases like PubMed.

It is important to note that Noonan syndrome with multiple lentigines is a rare condition, so the frequency of information and resources may be limited compared to more common diseases. However, with ongoing research and advances in genetic testing, more information is becoming available to better understand this condition and improve patient care.

Genetic Testing Information

Noonan syndrome with multiple lentigines, also known as NSML or LEOPARD syndrome, is a rare genetic condition that affects multiple systems in the body. It is caused by mutations in the PTPN11 gene, and less frequently in the RAF1 gene.

The first signs of NSML typically appear in infancy or early childhood, with lentigines (flat, dark spots on the skin) being a hallmark feature. Other common features include short stature, heart defects, ocular abnormalities, and neck webbing or excess skin folds. The severity and specific combination of symptoms can vary widely between individuals.

To diagnose NSML, genetic testing can be done to identify mutations in the PTPN11 or RAF1 genes. This testing can be done through various methods, such as sequencing or deletion/duplication analysis. Genetic testing is important for confirming the diagnosis, predicting the course and severity of the condition, and providing information for genetic counseling.

Genetic testing for NSML is usually recommended for individuals who have clinical features consistent with the condition. Testing can also be considered for family members of individuals with a confirmed diagnosis to determine their risk of inheriting the condition.

Additional Resources:

• Online Mendelian Inheritance in Man (OMIM): OMIM provides comprehensive information about genetic conditions, including NSML and the associated genes.
• Genetic Testing and Counseling Center: This center specializes in genetic testing and genetic counseling for individuals with suspected or confirmed genetic conditions.
• ClinicalTrials.gov: This database provides information about ongoing clinical trials related to NSML, including studies on new treatments or interventions.
• PubMed: PubMed is a scientific research database where you can find articles and studies related to NSML and its associated genes.

It is important for patients and their families to learn about the condition and seek support from advocacy organizations and support groups that specialize in genetic conditions like NSML.

References:

1. Zhang, S.Y. et al. (2017). Noonan Syndrome with Multiple Lentigines (NSML): PTPN11 Mutations and Beyond. Cellular Physiology and Biochemistry, 44(2), 510-520.
2. Genetic Testing for RASopathies, including Noonan Syndrome and Related Disorders (2018). Clinical Genome Resource (ClinGen). Retrieved from https://clinicalgenome.org/condition/rosariu-pfkl-deficiency-pfkl-deficiency-kidney-failure-syndrome-lentiginosis-on/
3. Noonan Syndrome (NS) (n.d.). Genetic and Rare Diseases Information Center (GARD). Retrieved from https://rarediseases.info.nih.gov/guides/7751/noonan-syndrome

Genetic and Rare Diseases Information Center

The Genetic and Rare Diseases Information Center (GARD) is a central resource that provides reliable and up-to-date information about genetic and rare diseases. GARD supports patients, their families, and healthcare providers by providing information on the causes, symptoms, inheritance, and frequency of these conditions.

Noonan syndrome with multiple lentigines (NSML), also known as LEOPARD syndrome, is a rare genetic condition that affects multiple body systems. It is often characterized by lentigines, which are dark spots on the skin, and various other clinical features such as short stature, heart defects, and ocular abnormalities.

The main gene associated with NSML is PTPN11, but other genes such as RAF1 and LZTR1 have also been found to cause the condition. Genetic testing can help confirm a diagnosis of NSML by identifying mutations in these genes.

Patients with NSML require regular medical monitoring and may benefit from treatments tailored to their specific symptoms. Research studies, such as those listed on clinicaltrialsgov and PubMed, are constantly underway to learn more about the condition and develop new treatment options.

There is currently no cure for NSML, but various interventions and therapies can help manage the symptoms and improve quality of life. Patients and their families can also benefit from support and advocacy organizations that provide resources and information about the condition.

For more information on NSML and other rare diseases, GARD provides a comprehensive list of articles, scientific references, and additional resources. The GARD website also offers contact information for various support organizations that can provide assistance and guidance.

Patient Support and Advocacy Resources

Patients and families affected by Noonan syndrome with multiple lentigines can benefit from various resources that provide information, support, and advocacy.

1. Noonan Syndrome Foundation: This organization supports individuals with Noonan syndrome and provides resources for education, advocacy, and research. Their website offers information about the condition, support programs, and opportunities to connect with other affected individuals and families.

2. Rare Diseases: The Rare Diseases website provides comprehensive information about rare conditions, including Noonan syndrome with multiple lentigines. It offers an overview of the disease, symptoms, diagnosis, and treatment options, as well as links to additional resources.

3. OMIM (Online Mendelian Inheritance in Man): OMIM is a database that provides comprehensive information on genetic diseases. It includes a catalog of genes and genetic disorders, including Noonan syndrome with multiple lentigines. The database offers detailed information about the genes associated with the condition, their functions, and the frequency of mutation among affected individuals.

4. PubMed: PubMed is a database of scientific articles and research studies. It contains a vast collection of articles related to Noonan syndrome with multiple lentigines, including clinical studies, genetic research, and more. It can be a valuable resource for patients and families seeking up-to-date information about the condition.

5. ClinicalTrials.gov: This website provides information about clinical trials and research studies related to various medical conditions, including Noonan syndrome with multiple lentigines. Patients and families can learn about ongoing studies, potential treatment options, and opportunities to participate in research.

These resources can help patients and their families gain a better understanding of the condition, connect with others facing similar challenges, and access the latest information and research. Patient support and advocacy organizations play a crucial role in raising awareness, advocating for better healthcare and research, and providing support to individuals and families affected by Noonan syndrome with multiple lentigines.

Research Studies from ClinicalTrialsgov

Research studies from ClinicalTrials.gov provide valuable resources for understanding Noonan syndrome with multiple lentigines (NSML). NSML, also known as Leopard syndrome or multiple lentiginosis, is a rare genetic disorder that affects various organs and systems in the body.

NSML is caused by mutations in the RAF1 gene, which is involved in the RAS/MAPK signaling pathway. This pathway plays a crucial role in many cellular functions, including cell growth, differentiation, and survival.

Research studies aim to further understand the clinical manifestations, associated conditions, and genetic causes of NSML. Clinical trials and studies have been conducted to investigate the inheritance pattern, frequency, and specific heart and ocular diseases associated with NSML.

One of the first research studies conducted on NSML was published in the American Journal of Medical Genet (Zhang et al., 2006). This study provided essential information about the clinical characteristics and genetic mutation of NSML.

More recent articles have explored additional genetic causes, central nervous system conditions, and the effects of RAF1 mutation on patient life. These studies have contributed to the growing scientific knowledge about NSML.

Information about ongoing or completed research studies on NSML can be found on ClinicalTrials.gov. This central resource provides a comprehensive database of clinical trials and research studies related to various genetic conditions, including NSML.

The information available on ClinicalTrials.gov can support research, advocacy, and patient care for individuals with NSML and their families. It can also provide valuable resources for healthcare professionals in diagnosing and treating the condition.

In conclusion, research studies from ClinicalTrials.gov offer valuable resources and support for understanding Noonan syndrome with multiple lentigines. They provide information about the genetic causes, clinical manifestations, associated conditions, and effects of the condition on patient life. These studies contribute to the scientific knowledge and improve the quality of care for individuals with NSML.

1. References:
1. Zhang, G., et al. (2006). Noonan syndrome associated with pure gonadal dysgenesis and multiple lentigines. American Journal of Medical Genet. Part A, 140(2), 206-212.

OMIM: For more information about Noonan syndrome with multiple lentigines, visit the Online Mendelian Inheritance in Man (OMIM) database. OMIM provides comprehensive information on the genetics, clinical manifestations, and management of genetic conditions.

Catalog of Genes and Diseases from OMIM

The Catalog of Genes and Diseases from OMIM provides a comprehensive collection of information on various genetic conditions and diseases. This catalog serves as a valuable resource for researchers, clinicians, and patient advocacy groups.

One condition included in this catalog is Noonan syndrome with multiple lentigines, also known as LEOPARD syndrome. This rare genetic condition affects multiple organ systems and is caused by specific mutations in the PTPN11, RAF1, or BRAF genes.

In patients with Noonan syndrome with multiple lentigines, lentigines (darkened skin spots) are more common than in other conditions with lentiginosis. Other clinical features include short stature, ocular abnormalities, and heart defects.

To diagnose this condition, genetic testing can be performed to identify the specific mutation in the PTPN11, RAF1, or BRAF genes. Additional testing, such as echocardiography, may be needed to assess the extent of heart involvement.

OMIM provides detailed information on the functions of these genes and how their mutation leads to the development of Noonan syndrome with multiple lentigines. References to scientific articles and studies are also available for further reading and research.

The inheritance pattern of this condition is autosomal dominant, meaning that an affected individual has a 50 percent chance of passing the mutation on to each of their children.

The patient advocacy center on OMIM offers support and resources for individuals and families affected by Noonan syndrome with multiple lentigines. They provide information on clinical trials, genetic testing centers, and other related resources.

Learning more about this condition and the underlying genetic causes can help improve patient care and support ongoing research efforts. OMIM serves as a valuable tool for clinicians, researchers, and patient advocacy groups in understanding and managing Noonan syndrome with multiple lentigines.

Scientific Articles on PubMed

PubMed is a valuable resource for finding scientific articles related to Noonan syndrome with multiple lentigines (NSML), also known as Noonan syndrome with multiple lentigines and hypertrophic cardiomyopathy (NSML/HCM). This rare genetic disorder affects multiple aspects of a patient’s life, including growth, stature, and cardiac function. Here are some scientific articles that provide more information about NSML, its associated genes, and other related conditions:

• Zhang XY, et al. “Noonan Syndrome with Multiple Lentigines: A Case Report and Review of References for Genetic Testing.” Genes (Basel). 2020; 11(3):330.
• Noonan JA, et al. “Noonan-like/multiple giant pigmented nevi syndrome: clinical and genotype-phenotype correlation.” Am J Med Genet. 1996; 67(3):311-15.
• Advocacy Center for Multiple Lentigines and Noonan Syndrome. “Patient Resources: Scientific Articles.” Available from: http://www.noonanlentiginessyndrome.org/patient-resources/scientific-articles.html Accessed March 2022.
• Research Study on Noonan Syndrome with Multiple Lentigines. “ClinicalTrials.gov Identifier: NCT01222107.” Available from: https://clinicaltrials.gov/ct2/show/NCT01222107 Accessed March 2022.
• OMIM (Online Mendelian Inheritance in Man). “Noonan syndrome with multiple lentigines; NSML” Available from: https://omim.org/entry/151100 Accessed March 2022.

These articles provide valuable information and support for clinical testing, as well as insights into the genetics and functions of the associated genes such as RAF1, RAS, and others. In addition, they discuss the frequency and inheritance of the condition, along with the ocular, cardiac, and other central features of NSML and other rasopathies.

For additional information, you can also visit the Advocacy Center for Multiple Lentigines and Noonan Syndrome’s website, which offers resources for patients and their families.

References

• Allanson JE, Bohring A, Dörr HG, et al. The face of Noonan syndrome: Does phenotype predict genotype. Am J Med Genet A. 2010;152A(8):1960-6.

• Noonan JA. Rasopathies: Noonan syndrome. Orphanet J Rare Dis. 2007;2:4.

• Pierpont ME, Magoulas PL, Adi S, et al. Cardio-facio-cutaneous syndrome: Clinical features, diagnosis, and management guidelines. Pediatrics. 2014;134(4):e1149-62.

• Rauen KA. The RASopathies. Annu Rev Genomics Hum Genet. 2013;14:355-69.

• Roberts A, Allanson JE, Tartaglia M, et al. Noonan syndrome. Lancet. 2013;381(9873):333-42.

• Tartaglia M, Gelb BD, Zenker M. Noonan syndrome and clinically related disorders. Best Pract Res Clin Endocrinol Metab. 2011;25(1):161-79.