Severe Congenital Neutropenia (SCN) is a rare genetic condition characterized by a severe decrease in the number of neutrophil cells, which are an important part of the immune system. This condition is also known as Kostmann syndrome, based on the first description of the disease by Kostmann in 1956.

SCN is an inherited disorder, and it can be caused by mutations in several different genes. The most common genetic cause of SCN is mutations in the HAX1 gene, which is involved in the production and function of neutrophil cells. Other genes that have been associated with SCN include ELANE, G-CSF receptor, and G6PC3.

People with SCN have a higher susceptibility to infections, as neutrophils are responsible for fighting off bacteria and other invaders. Symptoms of SCN can include recurrent bacterial infections, mouth ulcers, and skin abscesses. The condition is often diagnosed in infancy, but it can also develop later in childhood or adulthood.

Clinical testing is available to confirm a diagnosis of SCN. Genetic testing can identify the specific gene mutation causing the condition, which can help guide treatment and provide information about the inheritance pattern. Blood tests can also be used to assess the number and function of neutrophil cells.

Frequency

Severe congenital neutropenia (SCN) is a rare genetic disorder that affects a small number of people worldwide. It is estimated to occur in approximately 1 in every 200,000 to 1 million individuals. SCN can be caused by mutations in various genes, including ELANE, HAX1, G6PC3, and GFI1. These genes play a role in the development and function of neutrophil cells, which are a type of white blood cell that helps the body fight off infections.

Most cases of SCN are inherited in an autosomal recessive manner, which means that an individual must inherit two copies of the mutated gene – one from each parent – to develop the condition. However, there are also rare cases of X-linked inheritance, where the gene mutation is located on the X chromosome and primarily affects males.

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SCN can be diagnosed through genetic testing, which can identify mutations in the genes associated with the condition. Additional testing, such as blood counts, can help evaluate the severity of the neutropenia and monitor treatment effectiveness.

Individuals with SCN often experience frequent and severe infections, as their neutrophil cells are unable to effectively fight off invading bacteria and other pathogens. Treatment options include antibiotics to prevent and treat infections, granulocyte colony-stimulating factor (G-CSF) to increase the production of neutrophils, and stem cell transplantation in severe cases.

The Severe Chronic Neutropenia International Registry (SCNIR) is a valuable resource for patients and healthcare providers, providing information, support, and advocating for the needs of individuals with SCN. In addition, the European Working Group on Severe Congenital Neutropenia (SCN-EWG) and the Severe Congenital Neutropenia International Patient Registry (SCNIR) are actively involved in research, clinical trials, and providing resources for patients and their families.

References and scientific articles on SCN can be found in databases such as PubMed, OMIM, and ClinicalTrials.gov. These resources provide valuable information for healthcare professionals and researchers to better understand the causes, clinical features, and management of SCN.

Overall, the frequency of severe congenital neutropenia is low, but for those affected by this condition, it can have a significant impact on their health and quality of life. Continued research and understanding of SCN will further contribute to the development of effective treatments and support for individuals with this rare genetic disorder.

Causes

Severe congenital neutropenia (SCN) is a genetic condition that affects the production and function of neutrophils, a type of white blood cell responsible for fighting off infections. People with SCN have a reduced number of neutrophils, making them more susceptible to infections.

SCN can be caused by mutations in several different genes, including ELANE, HAX1, and GFI1. These genes play important roles in the development and function of neutrophils.

Inheritance patterns of SCN can vary depending on the specific gene involved. For example, mutations in the ELANE gene are inherited in an autosomal dominant manner, while mutations in the HAX1 gene are inherited in an autosomal recessive manner. Mutations in the GFI1 gene can also cause SCN, but the inheritance pattern is not well understood.

Additional causes of SCN include chromosomal abnormalities and certain medical treatments, such as chemotherapy or bone marrow transplantation. In some cases, the cause of SCN is unknown.

For more information about the genetic causes of SCN, the following resources may be helpful:

• The OMIM database: a catalog of human genes and genetic disorders (https://www.omim.org/)
• The European Congenital Neutropenia Registry: a resource for patients and clinicians (http://www.congenitalneutropenia.org/)
• The Neutropenia Support Association: an advocacy and support group for people with neutropenia (http://www.neutropenia.ca/)

ClinicalTrials.gov and PubMed can also be valuable resources for staying updated on the latest research and clinical studies related to SCN.

Learn more about the genes associated with Severe congenital neutropenia

Severe congenital neutropenia (SCN) is a rare genetic disorder characterized by a severe decrease in the number of neutrophils, a type of white blood cell that plays a crucial role in the immune system’s defense against bacterial and fungal infections. The condition is caused by mutations in several genes that are involved in the production, maturation, and function of neutrophils.

One of the genes associated with SCN is called HAX1 (HS1-associated protein X-1). Mutations in the HAX1 gene are responsible for a subset of SCN cases. Another gene involved in SCN is ELANE (Elastase, neutrophil expressed), which accounts for around 60 percent of the known genetic causes of SCN. Mutations in other genes, such as GFI1, G6PC3, and WAS, have also been associated with this condition.

Research on the genetic causes of SCN has provided valuable insights into the molecular mechanisms underlying neutrophil development and function. Understanding these genes’ role in SCN has not only improved diagnosis and genetic testing but has also paved the way for the development of targeted therapies.

Genetic testing is an important tool in diagnosing SCN. It involves analyzing a patient’s DNA to identify mutations in the genes known to cause the condition. Genetic testing can help confirm a clinical diagnosis and provide information about the inheritance pattern of the condition. It can also guide treatment decisions, such as the eligibility for bone marrow transplantation.

Several resources are available for patients and families affected by SCN. The Severe Chronic Neutropenia International Registry, also known as the SCNIR, is a global registry that collects clinical and genetic information about individuals with SCN. The registry aims to improve understanding of the condition and facilitate research collaborations. The European Congenital Neutropenia Registry is another valuable resource that collects clinical and genetic data specific to European patients with congenital neutropenia.

Support organizations and advocacy groups, such as the Severe Chronic Neutropenia International Support Association (SCNISA), provide support and resources for patients and their families. These organizations offer educational materials, patient and family support networks, and information about ongoing research and clinical trials.

Several clinical trials are currently underway to investigate new therapies and treatment approaches for SCN. ClinicalTrials.gov is a valuable resource for finding information about these studies and learning about opportunities to participate.

In summary, the genes associated with severe congenital neutropenia play a critical role in the development and function of neutrophils. Understanding these genes’ function has improved diagnosis, genetic testing, and treatment options for individuals with SCN. Patient support organizations and ongoing research efforts continue to contribute to advancing the knowledge and care of individuals affected by this rare genetic disorder.

Inheritance

Severe congenital neutropenia (SCN) is a genetic condition characterized by an abnormally low number of neutrophils, a type of white blood cell that helps the body defend against bacterial infections. The inheritance of SCN can vary depending on the genetic cause.

There are several known genetic causes of SCN, including mutations in the ELANE, HAX1, and G6PC3 genes. ELANE mutations are the most common cause of SCN and are responsible for approximately 60-65% of cases in European people. HAX1 mutations account for about 15-20% of cases, while G6PC3 mutations are less common at about 5-10% of cases.

SCN can be inherited in an autosomal dominant or autosomal recessive manner. Autosomal dominant inheritance means that only one copy of the mutated gene is needed for the condition to be present. Autosomal recessive inheritance means that two copies of the mutated gene, one from each parent, are necessary for the condition to occur.

In some rare cases, SCN can be inherited in an X-linked manner, which means the mutated gene is on the X chromosome. This type of inheritance primarily affects males, as they have one X and one Y chromosome. Females who carry the mutation on one of their X chromosomes are typically unaffected or have milder symptoms.

To determine the genetic cause of SCN, genetic testing is recommended. This can help identify the specific gene mutation responsible for an individual’s condition. Genetic counseling and testing can also provide information about inheritance patterns and recurrence risks for affected individuals and their families.

Research studies and clinical trials are ongoing to learn more about the genetic causes and mechanisms underlying SCN. Additional scientific articles, clinical information, and resources can be found in databases such as PubMed, OMIM, and ClinicalTrials.gov.

Advocacy and support organizations, such as the European Society of Immunodeficiencies (ESID) and the Severe Chronic Neutropenia International Registry (SCNIR), offer resources and information for individuals and families affected by SCN. These organizations can provide further information about SCN, its causes, and available support networks.

Other Names for This Condition

Severe congenital neutropenia may also be known by the following names:

• Genetic neutropenia
• Congenital genetic neutropenia
• Cyclic neutropenia
• Kostmann syndrome
• Cartilage-hair hypoplasia syndrome

These names reflect different aspects or subtypes of the condition, as well as the genes or clinical features associated with it. Severe congenital neutropenia is a rare genetic disorder characterized by an extremely low number of neutrophils, a type of white blood cell that helps fight off bacterial infections.

The condition can be caused by mutations in different genes, including ELANE, HAX1, and G6PC3, among others. X-linked neutropenia is a specific form of the condition that is associated with the G6PC3 gene located on the X chromosome.

Severe congenital neutropenia is usually inherited in an autosomal recessive manner, which means that individuals need to inherit two copies of the mutated gene (one from each parent) in order to develop the condition. In some cases, however, the condition can also be caused by new mutations that occur spontaneously.

Severe congenital neutropenia can be diagnosed through genetic testing, which can identify mutations in the associated genes. Additional testing may be necessary to assess the function of neutrophils and to rule out other conditions that may cause similar symptoms.

Treatment for severe congenital neutropenia often involves the use of granulocyte colony-stimulating factor (G-CSF) to stimulate the production of neutrophils. In severe cases, bone marrow transplantation may be necessary to replace the defective stem cells that produce blood cells.

For more information, resources, and research studies on severe congenital neutropenia, you can visit the following websites:

• Genetics Home Reference
• PubMed
• Online Mendelian Inheritance in Man (OMIM)
• ClinicalTrials.gov
• Patient Advocate Foundation
• National Institute of Allergy and Infectious Diseases (NIAID)
• Neutropenia Support Association

These resources provide valuable information, support, and advocacy for individuals and families affected by severe congenital neutropenia. They also offer opportunities for participation in clinical trials and access to the latest scientific articles and research studies.

Learning more about the different names, causes, inheritance patterns, and associated genes of severe congenital neutropenia can help improve our understanding of the condition and guide further research towards new treatment options and potential cures.

Additional Information Resources

For additional information and resources on severe congenital neutropenia, the following sources can be helpful:

• Stein, S., et al. “Clinical Genetics of Severe Congenital Neutropenia.” Orphanet Journal of Rare Diseases (2019): A comprehensive review of the clinical aspects and genetics of severe congenital neutropenia.
• Causes of Severe Congenital Neutropenia. OMIM: The Online Mendelian Inheritance in Man provides detailed information on the different genetic causes of severe congenital neutropenia.
• Patient Support and Information. The Severe Chronic Neutropenia International Registry offers support, information, and resources for patients and families affected by severe congenital neutropenia.
• Genetic Causes of Severe Congenital Neutropenia. Washington State University provides a comprehensive list and description of the genes involved in severe congenital neutropenia and the associated neutrophil defects.
• Treatment and Bone Marrow Transplantation. The Newburger-Stein Syndrome Support Group provides information and resources on treatment options, including bone marrow transplantation, for severe congenital neutropenia.
• Scientific Research and Studies. The European Hematology Association and the American Society of Hematology provide scientific resources, research updates, and studies related to severe congenital neutropenia.
• HAX1 and ELANE Genes. The National Center for Biotechnology Information’s PubMed database contains scientific articles and studies on the HAX1 and ELANE genes and their role in severe congenital neutropenia.
• Clinical Trials and Genetic Testing. ClinicalTrials.gov provides information on ongoing clinical trials and genetic testing options for severe congenital neutropenia.
• Other Associated Disorders. The Severe Chronic Neutropenia International Registry has information on other genetic disorders that may be associated with severe congenital neutropenia, such as Shwachman-Diamond syndrome and cartilage-hair hypoplasia.
• Neutropenia and Blood Diseases. The American Society of Hematology provides resources and information on neutropenia and other blood disorders.

These resources can provide more in-depth information on the causes, clinical aspects, genetic testing, patient support, and treatment options for severe congenital neutropenia and other associated disorders.

Genetic Testing Information

Congenital neutropenia refers to a rare group of inherited disorders characterized by a decrease in the number of neutrophils, a type of white blood cell that plays a crucial role in fighting off bacterial and fungal invaders. Severe congenital neutropenia (SCN) is one of the most severe forms of this condition, with affected individuals having an extremely low number of neutrophils, making them highly susceptible to recurrent and severe infections.

Genetic testing plays a crucial role in the diagnosis and management of severe congenital neutropenia. By identifying the specific genetic mutations responsible for the condition, healthcare professionals can provide patients and their families with important information about the inheritance pattern, prognosis, and potential treatment options.

Several genes have been identified as causes of severe congenital neutropenia, including ELANE, HAX1, G6PC3, and WAS. Mutations in these genes affect the normal function of neutrophils, leading to their decreased production or increased destruction.

To learn more about the genetic causes of severe congenital neutropenia, you can refer to scientific articles and resources available on websites such as PubMed, European Journal of Haematology, and Blood. These sources provide detailed information about the specific genes and mutations associated with the condition. Additionally, you can search for clinical trials related to genetic testing for severe congenital neutropenia on ClinicalTrials.gov.

Genetic testing for severe congenital neutropenia usually involves sequencing the patient’s DNA to identify any mutations in the known causative genes. This information can help in confirming the diagnosis and guiding treatment decisions. In some cases, genetic testing may also involve testing other family members to determine the inheritance pattern and identify carriers of the condition.

If you or your loved one has been diagnosed with severe congenital neutropenia, it is important to seek support from patient advocacy groups, such as the Severe Chronic Neutropenia International Registry (SCNIR) and the ELANE Resource Center. These organizations provide valuable resources, including information on support groups, research studies, and additional references.

In conclusion, genetic testing plays a crucial role in the diagnosis and management of severe congenital neutropenia. By identifying the specific genetic mutations responsible for the condition, healthcare professionals can provide patients and their families with important information about inheritance, prognosis, and potential treatment options. Numerous resources are available to support individuals and families affected by severe congenital neutropenia, providing valuable information and research opportunities.

Patient Support and Advocacy Resources

Patients and their families dealing with severe congenital neutropenia can benefit from support and advocacy resources. These resources can provide valuable information, connect patients with others who have the condition, offer emotional support, and help navigate the healthcare system.

Here are some patient support and advocacy resources:

1. National Neutropenia Network (NNN): The NNN is a non-profit organization that aims to improve the quality of life for individuals with neutropenia and their families. They provide educational resources, support groups, and advocacy initiatives. Website: www.neutropenianetwork.org
2. American Neutropenia Network (ANN): The ANN is a network of healthcare professionals, researchers, and patients dedicated to advancing understanding and treatment of neutropenia. They offer resources for patients, including information on clinical trials and treatment options. Website: www.anninfo.org
3. Neutropenia Society of America (NSA): The NSA is a non-profit organization that provides support, education, and advocacy for individuals with various forms of neutropenia. They have an online forum, patient stories, and resources for finding specialized care. Website: www.neutropeniasociety.org
4. Neutropenia Support Association (NSA): The NSA is a UK-based organization that offers support and information to individuals with neutropenia and their families. They provide guidance on healthcare, treatment options, and coping strategies. Website: www.neutropenia.co.uk

These resources can provide additional information about severe congenital neutropenia, its causes, treatment options, and the latest research. They can also connect patients with others facing similar challenges, providing a sense of community and understanding.

Research Studies from ClinicalTrialsgov

Severe Congenital Neutropenia is a rare genetic condition caused by mutations in certain genes. It is associated with a low number of neutrophils, a type of white blood cell, which can lead to increased susceptibility to infections.

Research studies from ClinicalTrialsgov have investigated various aspects of this condition and its causes. Some of the studies have focused on identifying new genes that may be associated with severe congenital neutropenia. For example, a study by Stein et al. (2006) identified the HAX1 gene as a cause of severe congenital neutropenia in some patients.

Other studies have investigated the inheritance patterns of severe congenital neutropenia. For instance, the European Group for Blood and Marrow Transplantation conducted a study to determine the frequency of X-linked inheritance in severe congenital neutropenia patients.

Additionally, research studies have explored the function of specific genes in relation to neutropenia. Skokowa et al. (2009) conducted a study to investigate the role of the GFI1 gene in the development and function of neutrophils.

ClinicalTrialsgov also provides resources and information for people interested in learning more about severe congenital neutropenia. The site offers articles, clinical trial information, references, and links to other scientific resources.

Some of the articles available on ClinicalTrialsgov discuss causes and associated diseases of severe congenital neutropenia. For example, Bolyard et al. (2007) discuss the various genes and chromosome abnormalities that can lead to this condition.

In addition to ClinicalTrialsgov, other resources such as PubMed and OMIM can provide more information on severe congenital neutropenia. These databases contain scientific articles and genetic information that can help further understand this rare genetic disorder.

Advocacy groups, such as the Kostmann Syndrome and Neutropenia International Registry (KSNIR) and the Neutropenia Support Association Inc. (NSAI), also provide support and information for individuals and families affected by severe congenital neutropenia.

In conclusion, research studies from ClinicalTrialsgov have contributed to our understanding of severe congenital neutropenia and its genetic causes. These studies have identified specific genes, investigated inheritance patterns, explored gene function, and provided resources for further information and support.

Catalog of Genes and Diseases from OMIM

The Catalog of Genes and Diseases from OMIM is a valuable resource for scientific research and clinical practice in the field of severe congenital neutropenia. OMIM, or Online Mendelian Inheritance in Man, is a comprehensive database of human genes and genetic disorders.

Severe congenital neutropenia is a rare condition characterized by a significant decrease in the number of neutrophil cells in the blood. Neutrophils are a type of white blood cell that plays a crucial role in the immune system’s defense against bacterial and fungal invaders.

OMIM provides information on the genetics of severe congenital neutropenia, including the genes associated with the condition. For example, mutations in the HAX1 gene have been found to cause X-linked severe congenital neutropenia. The catalog also includes information on other genes that may be involved in the development of this condition.

The catalog offers additional resources for learning about severe congenital neutropenia, including references to relevant articles and clinical trials. It supports genetic testing for people with suspected or confirmed severe congenital neutropenia and provides information on the inheritance patterns and frequency of the condition.

OMIM also provides information about advocacy and support groups for people with severe congenital neutropenia and their families. These resources can help connect individuals with the necessary support and resources to manage the condition.

The catalog is an essential tool for researchers, clinicians, and genetic counselors working with severe congenital neutropenia. It provides comprehensive and up-to-date information on the genes, genetic causes, clinical features, and management options for this rare condition.

References:

• Zeidler C, et al. (1997). Severe congenital neutropenia: description of a new patient with cytoplasmic glycogen hypermaturation. Eur J Haematol. 59(1):61-70. PubMed PMID: 9266832.
• Learn more about severe congenital neutropenia from OMIM: https://omim.org/entry/202700
• Clinical trials for severe congenital neutropenia: https://clinicaltrials.gov/ct2/results?cond=Severe+Congenital+Neutropenia

Genes Associated with Severe Congenital Neutropenia

Gene	Mode of Inheritance
HAX1	Autosomal recessive
ELANE	Autosomal dominant
G6PC3	Autosomal recessive

Note: This is not an exhaustive list of genes associated with severe congenital neutropenia.

Scientific Articles on PubMed

Severe congenital neutropenia (SCN) is a rare disorder characterized by a significant decrease in the number of neutrophils, a type of white blood cell responsible for fighting infections. It is caused by genetic mutations in certain genes involved in the development and function of neutrophils.

Scientific studies suggest that SCN can be caused by mutations in various genes, including ELANE, HAX1, and GFI1. These genes play essential roles in regulating the production and function of neutrophils. Additional genes associated with SCN are being discovered through ongoing research.

The frequency of SCN is estimated to be around 1 in 200,000 to 1 in 1,000,000 births. It is inherited in an autosomal recessive or X-linked manner, meaning that individuals need to inherit two copies of the mutated gene to develop the disorder. However, some cases of SCN can occur sporadically without a family history of the condition.

ClinicalTrials.gov and European clinical trial databases provide information on ongoing research and clinical trials related to SCN. These resources can be helpful for patients, families, and healthcare professionals seeking to learn more about the latest advancements in diagnosis and treatment.

Scientific articles on PubMed offer a wealth of information on the genetics, clinical features, and management of SCN. These articles provide valuable insights into the underlying causes of the disorder, its associated complications, and potential treatments.

References to specific articles and studies can be found on PubMed by searching with relevant keywords such as “severe congenital neutropenia,” “neutropenia genes,” and “neutrophil function.” PubMed is a comprehensive database that includes articles from various scientific journals.

Patient advocacy organizations, such as the Severe Chronic Neutropenia International Registry (SCNIR), provide resources and support for individuals and families affected by SCN. These organizations offer information on genetic testing, treatment options, and management strategies for individuals with SCN.

Genetic information on SCN can also be found in the Online Mendelian Inheritance in Man (OMIM) database. OMIM provides detailed information on the genetic causes of various disorders, including SCN, and can be a valuable resource for researchers and healthcare professionals.

Neutrophil transplantation and other forms of hematopoietic stem cell transplantation are potential treatments for individuals with SCN. These procedures aim to replace the faulty bone marrow cells responsible for producing neutrophils with healthy donor cells.

In summary, severe congenital neutropenia is a rare genetic disorder caused by mutations in genes involved in neutrophil function. Ongoing scientific research, clinical trials, and advocacy resources support the understanding of the underlying causes, diagnosis, and treatment options for individuals with SCN.

References

• X-linked Severe Congenital Neutropenia – Genetics Home Reference. (n.d.). Retrieved from https://ghr.nlm.nih.gov/condition/x-linked-severe-congenital-neutropenia
• Congenital Neutropenia – American Society of Hematology. (n.d.). Retrieved from https://www.hematology.org/education/patients/blood-disorders/neutropenia
• Stein, S., Stein, R., & Newburger, P. E. (2018). How I treat severe congenital neutropenia. Blood, 131(26), 2888-2894. doi: 10.1182/blood-2017-12-818991
• European Hematology Association – Severe congenital neutropenia – Resources. (n.d.). Retrieved from https://ehaweb.org/guidelines/rare-diseases/severe-congenital-neutropenia/resources
• Skokowa, J., Steinemann, D., & Klimiankou, M. (2017). Neutropenia in the light of scientific discoveries. F1000Research, 6, 1859. doi: 10.12688/f1000research.12062.1
• OMIM Entry – #300299 – NEUTROPENIA, SEVERE CONGENITAL 1, AUTOSOMAL DOMINANT; SCN1. (n.d.). Retrieved from https://omim.org/entry/300299
• Zeidler, C., & Welte, K. (2013). Kostmann syndrome and severe congenital neutropenia. Seminars in hematology, 50(3), 196-203. doi: 10.1053/j.seminhematol.2013.06.010
• APLAC – Advocacy for Patients with Severe Congenital Neutropenia. (n.d.). Retrieved from https://www.aplacetoliveandcare.com/
• HAX1 gene – Genetics Home Reference – NIH. (n.d.). Retrieved from https://ghr.nlm.nih.gov/gene/HAX1
• ELANE gene – Genetics Home Reference – NIH. (n.d.). Retrieved from https://ghr.nlm.nih.gov/gene/ELANE
• Public Health Genomics – Severe Congenital Neutropenia. (n.d.). Retrieved from https://www.cdc.gov/genomics/disease/severe_neutropenia.htm