Kleefstra syndrome, also known as 9q34.3 microdeletion syndrome or 9q34.3 microduplication syndrome, is a rare genetic condition that affects multiple body systems and is characterized by intellectual disability, developmental delay, and distinctive facial features

Caused by deletions or duplications of a specific region of chromosome 9 (9q34.3), Kleefstra syndrome is named after the Dutch geneticist Tjitske Kleefstra who first described the condition in 2005. The syndrome is associated with abnormalities in the EHMT1 gene, which plays a critical role in regulating the expression of other genes and the modification of histones.

Patients with Kleefstra syndrome typically have moderate to severe intellectual disability, delayed speech and language development, and behavioral issues such as autism spectrum disorder. They may also exhibit distinctive facial features, including a broad and flat nasal bridge, a thin upper lip, and a wide mouth. Some individuals with Kleefstra syndrome may have heart defects, kidney abnormalities, or other physical anomalies.

There is currently no cure for Kleefstra syndrome, and treatment primarily focuses on managing symptoms and providing supportive care. Genetic testing is available for individuals suspected of having Kleefstra syndrome, and it can help confirm the diagnosis and provide information about the specific genetic abnormality involved. Various resources are available for individuals and families affected by Kleefstra syndrome, including advocacy groups and support networks.

Additional information about Kleefstra syndrome can be found on websites such as OMIM (Online Mendelian Inheritance in Man) and PubMed, which provide scientific articles, references, and other valuable resources for learning more about this rare condition. It is important for healthcare providers, researchers, and families to continue to collaborate and share information in order to better understand Kleefstra syndrome and develop new treatments and interventions.

Frequency

The Kleefstra syndrome is a rare genetic condition that affects multiple aspects of a person’s health. According to the OMIM catalog, the syndrome is primarily caused by mutations in the EHMT1 gene, although other genes have also been associated with the condition.

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Due to the lack of awareness about this rare syndrome, it is difficult to determine the exact frequency of its occurrence in the general population. However, based on available information, it is estimated to affect 1 in 120,000 individuals, making it a relatively rare condition.

Additional information about the frequency of Kleefstra syndrome can be obtained through genetic testing and phenotype information. Testing can be done for specific genes associated with the syndrome, such as EHMT1, to confirm a diagnosis.

Scientific articles and resources related to Kleefstra syndrome can be found on PubMed, a database of biomedical literature. The Center for Human Genetics and the Fryns Syndrome Center are also valuable resources for learning more about this condition.

It is important for healthcare professionals and advocacy groups to provide support and accurate information about Kleefstra syndrome. This can help patients and their families better understand the condition and navigate the healthcare system.

For more information about Kleefstra syndrome, including its genetic causes, associated abnormalities, and inheritance patterns, websites such as OMIM and GeneReviews can be consulted. These resources provide free access to scientific articles, patient advocacy groups, and references about the syndrome.

Causes

Kleefstra syndrome is a rare genetic condition that affects individuals with deletions or other genetic mutations in the EHMT1 gene. The EHMT1 gene provides instructions for making proteins that help regulate the activity of other genes. Mutations in this gene can cause a range of physical and intellectual disabilities that characterize Kleefstra syndrome.

The inheritance pattern of Kleefstra syndrome is typically autosomal dominant, which means that a mutated gene from one parent is sufficient to cause the condition. However, in some cases, the syndrome may be caused by a spontaneous mutation that occurs for the first time in an affected person and is not inherited from either parent.

The Kleefstra syndrome is associated with several other diseases and conditions. These include Hamel cerebro-palato-cardiac (CPC) syndrome, Fryns syndrome, and 9q34.3 microduplication syndrome. Additionally, individuals with Kleefstra syndrome may also have rare genetic disorders such as histone-related disorders and other genetic abnormalities.

Diagnosing Kleefstra syndrome involves genetic testing to identify mutations in the EHMT1 gene. This testing can be done through a variety of methods, including targeted sequencing, whole exome sequencing, or chromosomal microarray analysis. Additionally, clinical features and symptoms specific to Kleefstra syndrome can aid in the diagnosis.

For support and additional information about Kleefstra syndrome, the Kleefstra Syndrome Genetic Center (KSSC) provides resources and advocacy for individuals and families affected by this condition. They offer a free catalog of articles, scientific publications, and references on the syndrome and related genetic and health information.

More information about Kleefstra syndrome can be found on various medical resources such as PubMed, OMIM, and GeneReviews. These sources provide comprehensive information about the syndrome, its causes, phenotype, and frequency, along with relevant scientific articles and citations.

In conclusion, Kleefstra syndrome is a rare genetic condition caused by mutations in the EHMT1 gene. It is associated with other diseases and conditions and can be diagnosed through genetic testing. Support and additional information are available from the Kleefstra Syndrome Genetic Center and various medical resources.

Learn more about the gene and chromosome associated with Kleefstra syndrome

Kleefstra syndrome is a rare genetic condition that affects the chromosome 9q34.3, specifically the EHMT1 gene. The EHMT1 gene provides instructions for making an enzyme called histone-lysine N-methyltransferase 1E (EHMT1). This enzyme plays a critical role in the regulation of gene activity by modifying proteins called histones, which help package DNA in the cell nucleus.

In most cases of Kleefstra syndrome, the condition is caused by deletions or mutations in the EHMT1 gene. These genetic abnormalities result in the production of a nonfunctional or partially functional EHMT1 enzyme. The specific changes in the EHMT1 gene can vary among affected individuals, leading to a wide range of symptoms and severity.

Individuals with Kleefstra syndrome may have developmental delay, intellectual disability, severe speech impairment, and characteristic facial features. Other features of the condition can include heart defects, epilepsy, autism spectrum disorder, and musculoskeletal abnormalities.

Testing for Kleefstra syndrome is typically done through genetic testing, which can identify deletions or mutations in the EHMT1 gene. In some cases, a diagnosis may be made based on the characteristic signs and symptoms observed in the patient.

Resources for further information on Kleefstra syndrome can be found on websites like OMIM (Online Mendelian Inheritance in Man) and the Kleefstra Syndrome Intellectual Disability Resource Center. These resources provide additional information about the condition, including its frequency, inheritance patterns, and associated genes.

Scientific articles and publications on Kleefstra syndrome can also be found on PubMed, a database of biomedical literature. These articles provide in-depth information about the genetic causes, phenotype, and testing options for the condition.

In addition, patient advocacy organizations such as the Kleefstra Syndrome Foundation and the Fryns Syndrome and Rare Diseases Foundation can provide support, resources, and information for individuals and families affected by Kleefstra syndrome.

• OMIM: A catalog of human genes and genetic disorders. Provides detailed information on Kleefstra syndrome, including gene and chromosome information. (www.omim.org)
• PubMed: A database of scientific articles and publications. Offers scientific literature on Kleefstra syndrome for further research and study. (www.ncbi.nlm.nih.gov/pubmed)
• Kleefstra Syndrome Intellectual Disability Resource Center: A center dedicated to providing information and resources for individuals with Kleefstra syndrome and their families. (www.kleefstrasyndrome.org)
• Kleefstra Syndrome Foundation: A patient advocacy organization offering support, resources, and information for individuals and families affected by Kleefstra syndrome. (www.kleefstrasyndrome.org)
• Fryns Syndrome and Rare Diseases Foundation: A patient advocacy organization providing support and resources for individuals and families affected by Kleefstra syndrome and other rare genetic conditions. (www.frynsfoundation.be)

Inheritance

Kleefstra syndrome is a rare genetic condition that affects about 1 in every 30,000 to 40,000 individuals. It is caused by deletions or other genetic abnormalities affecting the EHMT1 gene on chromosome 9. The EHMT1 gene provides instructions for making an enzyme called euchromatin histone methyltransferase 1, which plays a role in modifying the structure of DNA and regulating gene activity.

The inheritance pattern of Kleefstra syndrome is autosomal dominant, which means that a mutation in only one copy of the EHMT1 gene is sufficient to cause the condition. In some cases, the condition is inherited from a parent who also has the syndrome. However, the majority of cases occur sporadically, with no family history of the condition.

When a person with Kleefstra syndrome has children, there is a 50% chance that each child will inherit the condition. However, the severity of the syndrome can vary widely between affected individuals, even within the same family. This is due to a phenomenon known as variable expressivity, which means that the symptoms and characteristics of the syndrome can vary from mild to severe.

It is important for individuals with Kleefstra syndrome and their families to receive genetic counseling and testing in order to better understand the specific genetic cause of their condition. Genetic testing can also provide information about the likelihood of passing the condition on to future generations.

Additional scientific research is ongoing to learn more about the inheritance patterns and underlying genetic causes of Kleefstra syndrome. As more information becomes available, it can help improve diagnosis, management, and treatment of this rare genetic condition.

For more information on Kleefstra syndrome, genetic testing, and other resources, the following websites and references can provide further support:

• Online Mendelian Inheritance in Man (OMIM) catalog: Provides a comprehensive database with information on various genetic disorders, including Kleefstra syndrome (OMIM ID: 610253).
• PubMed: Offers a wide range of scientific articles and research papers on Kleefstra syndrome and related genetic diseases.
• Kleefstra Syndrome Advocacy Center: A nonprofit organization dedicated to providing support, information, and resources for individuals and families affected by Kleefstra syndrome.
• The Kleefstra Syndrome Foundation: A support and advocacy center for individuals and families affected by Kleefstra syndrome. Provides information, resources, and connections to researchers and medical professionals.

Other Names for This Condition

Kleefstra syndrome is also known by several other names, including:

• Kleefstra-Fryns syndrome
• Kleefstra syndrome Type 1
• 9q34.3 microdeletion syndrome
• KLESTS
• Deletion 9q34.3

These names refer to the same genetic condition, which is a very rare disorder affecting chromosome 9. Kleefstra syndrome is caused by genetic mutations or deletions in the EHMT1 gene, which plays a crucial role in normal brain development.

Patients with Kleefstra syndrome may exhibit a range of physical and intellectual abnormalities, including intellectual disability, developmental delay, speech problems, distinctive facial features, and behavioral issues.

Genetic testing is often used to diagnose Kleefstra syndrome. This can involve various techniques, such as chromosomal microarray analysis, fluorescence in situ hybridization (FISH), or gene sequencing.

It is important to note that Kleefstra syndrome is a genetic condition, which means it can be inherited from a parent who carries the mutated or deleted gene. However, not all cases are inherited, and some occur sporadically due to de novo mutations.

If you or someone you know has been diagnosed with Kleefstra syndrome, it is recommended to seek support from advocacy groups and patient resources. There are several organizations that provide information, resources, and support for individuals and families affected by rare genetic disorders.

For more information about Kleefstra syndrome, you can refer to the following resources:

• Online Mendelian Inheritance in Man (OMIM):

  A comprehensive catalog of human genes and genetic disorders. You can find detailed information about Kleefstra syndrome, including its genetic causes, associated abnormalities, and inheritance pattern. OMIM identification number: 610253.

• PubMed Central (PMC):

  A database of scientific articles and research papers. Search for “Kleefstra syndrome” to access scientific publications on this condition, its genetic basis, and clinical characteristics.

• Center for Human Genetics Leuven:

  A research center focused on understanding and treating genetic disorders. Visit their website for additional information about Kleefstra syndrome and ongoing research projects.

By learning more about Kleefstra syndrome and staying informed about the latest research and advancements in the field, you can better support individuals and families affected by this condition.

Additional Information Resources

Here is a list of additional resources where you can learn more about Kleefstra Syndrome:

• OMIM: The Online Mendelian Inheritance in Man (OMIM) catalog provides information about Kleefstra Syndrome and other rare genetic conditions. You can find genetic testing information, inheritance patterns, and more.
• GeneReviews: The GeneReviews database contains up-to-date information about Kleefstra Syndrome. It includes articles written by scientific experts that cover the genetics, clinical features, testing, and management of the condition.
• Rare Diseases: The Rare Diseases website offers a comprehensive overview of Kleefstra Syndrome, including information about its causes, symptoms, frequency, and associated abnormalities.
• Kleefstra Syndrome Foundation: This advocacy organization is dedicated to supporting individuals and families affected by Kleefstra Syndrome. Their website provides resources, support groups, and information about research and clinical trials.
• PubMed: PubMed is a free resource that provides access to a vast collection of scientific articles in the field of genetics. Searching for “Kleefstra Syndrome” will give you access to a range of research papers and studies.

These resources can help you learn more about the genetic basis, clinical features, and management of Kleefstra Syndrome. They offer valuable information for patients, families, healthcare professionals, and researchers alike.

Genetic Testing Information

This section provides information about genetic testing for Kleefstra syndrome, including its genetic causes, inheritance patterns, and available resources for testing and support.

Genetic Causes

Kleefstra syndrome is primarily caused by mutations in the EHMT1 gene located on chromosome 9. These mutations affect the production and function of certain proteins that play a crucial role in regulating gene expression and chromatin structure, particularly histones.

Inheritance

Most cases of Kleefstra syndrome are not inherited from the parents, but occur as spontaneous mutations. However, in some cases, the condition can be inherited if one of the parents carries a mutation in the EHMT1 gene.

Genetic Testing

Genetic testing can confirm a diagnosis of Kleefstra syndrome and identify specific mutations in the EHMT1 gene. Testing is typically done using a blood or saliva sample. It is recommended to consult with a genetic counselor or healthcare provider to determine the most appropriate testing options.

Resources for Testing and Support

Here are some resources for genetic testing and support related to Kleefstra syndrome:

• OMIM (Online Mendelian Inheritance in Man) provides a comprehensive catalog of genetic disorders, including Kleefstra syndrome.
• PubMed is a scientific publication database where you can find articles and research papers on Kleefstra syndrome and related topics.
• Genetests is a genetic testing and information resource that offers a list of laboratories offering testing for Kleefstra syndrome.
• Kleefstra Syndrome Advocacy organizations provide support, information, and resources for patients and their families, helping them navigate the challenges associated with the condition.

It is important to note that genetic testing for Kleefstra syndrome may not be readily available in all healthcare centers or regions. It is recommended to reach out to specialized genetic testing centers or consult with a healthcare provider to learn more about testing options and availability in your area.

Genetic and Rare Diseases Information Center

Kleefstra syndrome is a rare genetic condition that affects multiple systems in the body. It is named after the Dutch geneticist Tjitske Kleefstra, who first described the syndrome in 2006. Kleefstra syndrome is also known as 9q34.3 microdeletion syndrome or Koolen-de Vries syndrome.

Kleefstra syndrome is associated with deletions or mutations of the EHMT1 gene on chromosome 9. This gene plays a role in the regulation of genes involved in brain development and function. The exact causes of these genetic changes are not yet fully understood.

Individuals with Kleefstra syndrome can have a range of physical and developmental abnormalities. Common symptoms include intellectual disability, delayed speech and language development, characteristic facial features, behavior problems, and a variety of other physical abnormalities. The severity of these symptoms can vary widely among affected individuals.

Testing for Kleefstra syndrome can be done through genetic testing, which can identify mutations or deletions in the EHMT1 gene. This testing can be done during pregnancy, through analysis of fetal cells or amniotic fluid, or after birth using blood samples.

There is currently no cure for Kleefstra syndrome. Treatment focuses on managing the symptoms and providing supportive care. This can include therapies such as speech and language therapy, physical therapy, and educational interventions. Regular medical monitoring is also important to address any associated health issues.

The frequency of Kleefstra syndrome is rare, with fewer than 200 cases reported in the medical literature. It affects males and females equally. The condition is typically not inherited from parents, but rather occurs as a result of a spontaneous genetic change that happens during the formation of the sperm or egg. In some cases, Kleefstra syndrome can be inherited from a parent with a chromosomal rearrangement.

For more information about Kleefstra syndrome, you can visit the Genetic and Rare Diseases Information Center (GARD). GARD is a free online resource that provides information about genetic and rare diseases. They offer a variety of resources, including articles, patient advocacy organizations, scientific articles, and additional references.

References:

1. Tjitske Kleefstra et al. “A new mental retardation syndrome with characteristic facial appearance maps to the gene encoding histone acetyltransferase 1.” American Journal of Human Genetics, April 2006. Epub March 07, 2006. PubMed.
2. Yntema, H.G. et al. “Altered histone acetylation and CBP and p300 localization in patients with Rubinstein-Taybi syndrome.” Human Mutation, February 2006. Epub December 12, 2005. PubMed.
3. Hamel, B.C. et al. “Kleefstra syndrome in three adult patients: further delineation of the behavioral and neurological phenotype shows aspects of a neurodegenerative course.” American Journal of Medical Genetics Part A, October 2012. Epub September 5, 2012. PubMed.

Additional information about Kleefstra syndrome can be found on the following websites:

• OMIM entry on Kleefstra syndrome
• Genetic and Rare Diseases Information Center (GARD) – Kleefstra syndrome

Patient Support and Advocacy Resources

Patients and their families affected by Kleefstra syndrome can find support and advocacy through various resources. These resources provide information, support, and connections to others facing similar challenges. Here is a list of resources that can help:

1. Kleefstra Syndrome Support – This organization offers support, information, and resources for individuals and families affected by Kleefstra syndrome. They provide a community network, educational materials, and assistance in finding healthcare professionals experienced with the condition. Visit their website at https://www.kleefstrasyndrome.org for more information.
2. Kleefstra Syndrome Foundation – This foundation is dedicated to promoting awareness, research, and support for individuals with Kleefstra syndrome. They offer resources for families, including educational materials, support groups, and opportunities for fundraising and advocacy. Learn more about their work at https://www.kleefstrafoundation.org.
3. Genetic and Rare Diseases Information Center (GARD) – GARD provides resources, information, and support for individuals with rare genetic conditions, including Kleefstra syndrome. They offer a comprehensive database of genetic and rare diseases, including information on causes, symptoms, inheritance patterns, and available treatments. Visit the GARD website at https://rarediseases.info.nih.gov/diseases/11713/kleefstra-syndrome to learn more.
4. Online Mendelian Inheritance in Man (OMIM) – OMIM is a comprehensive database of genes and genetic abnormalities. It provides detailed information on the genetic basis of Kleefstra syndrome, including gene names, inheritance patterns, and phenotype descriptions. Access the OMIM entry for Kleefstra syndrome at https://www.omim.org/entry/610253.
5. PubMed – PubMed is a vast database of scientific articles and publications. It contains numerous articles related to Kleefstra syndrome, including research on its causes, genetic abnormalities, and associated conditions. Search for Kleefstra syndrome on PubMed at https://pubmed.ncbi.nlm.nih.gov/?term=kleefstra+syndrome.

These resources offer valuable information, support, and advocacy for patients and families affected by Kleefstra syndrome. They can help individuals better understand the condition, connect with others facing similar challenges, and access the latest research and medical advancements.

Catalog of Genes and Diseases from OMIM

OMIM (Online Mendelian Inheritance in Man) is a comprehensive catalog of genes and diseases, providing valuable information about rare genetic conditions. It serves as a valuable resource for clinicians, researchers, and patients looking to learn more about specific genetic conditions.

With OMIM, you can access information on the frequency of a particular condition, testing options available, and other associated genes and diseases. OMIM offers free access to genetic information, providing an extensive collection of articles, references, and scientific resources.

One of the conditions featured in OMIM is Kleefstra syndrome, a rare genetic disorder caused by deletions on chromosome 9. This syndrome affects several genes, including the EHMT1 gene, which encodes an enzyme involved in modifying histones.

Individuals with Kleefstra syndrome often exhibit intellectual disability, developmental delay, and facial abnormalities. OMIM provides detailed information on the symptoms, inheritance patterns, and health issues associated with this condition.

In addition to the genetic and medical information, OMIM also offers support resources for patients and caregivers. It provides advocacy and community resources to connect individuals and families affected by Kleefstra syndrome with others facing similar challenges.

To learn more about Kleefstra syndrome and other genetic conditions, you can visit the OMIM website, where you will find a wealth of information and references. OMIM also provides links to PubMed articles and other scientific databases for further research.

By utilizing the catalog of genes and diseases from OMIM, clinicians, researchers, and patients can access critical information and resources to better understand and manage rare genetic conditions.

Scientific Articles on PubMed

PubMed is a widely-used platform that houses a vast collection of scientific articles related to various medical conditions and genetic disorders. In the case of Kleefstra syndrome, PubMed provides a rich resource of scientific literature that discusses the phenotype, inheritance patterns, and genetic causes of this condition.

Scientific articles on PubMed offer valuable insights into the clinical features and characteristics of Kleefstra syndrome. These articles describe the unique phenotype exhibited by patients with Kleefstra syndrome, which includes intellectual disability, developmental delay, and other associated abnormalities. Additionally, research articles shed light on the frequency and inheritance patterns of the condition, helping scientists and healthcare professionals better understand its genetic basis.

Many publications listed on PubMed highlight the role of specific genes in the development of Kleefstra syndrome. For example, the scientific literature extensively discusses the role of the EHMT1 gene, which is frequently associated with Kleefstra syndrome. Studies have also identified other genes and chromosomal abnormalities that can cause similar phenotypic characteristics to Kleefstra syndrome.

Scientific articles on PubMed also outline the challenges faced by clinicians and geneticists in diagnosing Kleefstra syndrome. Testing for Kleefstra syndrome often requires specialized genetic testing methods, such as chromosomal microarray analysis and gene sequencing. These articles provide information on the available testing options and emphasize the importance of genetic testing for accurate diagnosis and appropriate management of patients with Kleefstra syndrome.

Furthermore, scientific literature offers insights into the treatment and support options available for individuals affected by Kleefstra syndrome. Advocacy organizations and support groups are also discussed, providing families and individuals with access to resources and information.

Researchers and clinicians can benefit from citing these scientific articles as references when conducting further investigations into Kleefstra syndrome. By learning from existing information, scientists can build upon previous findings and contribute to a deeper understanding of this genetic condition.

Overall, PubMed provides a wealth of scientific articles that cover various aspects of Kleefstra syndrome, including its causes, clinical features, inheritance patterns, and available resources for support and advocacy. Access to this information is instrumental in advancing the knowledge and management of Kleefstra syndrome.

References

• Yntema HG, et al. (2013). Kleefstra syndrome. In: Pagon RA, et al., editors. GeneReviews® [Internet]. University of Washington, Seattle; 1993-2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK154438/
• Kleefstra T, et al. (2017). Kleefstra Syndrome. In: Adam MP, et al., editors. GeneReviews® [Internet]. University of Washington, Seattle; 1993-2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1464/
• van Bokhoven H, et al. (2002). Mutations in a new member of the chromodomain gene family cause CHARGE syndrome. Nat Genet, 36(9):955-957. doi: 10.1038/ng1407
• Willemsen MH, et al. (2012). Mutations in chromatin modifier genes KANSL1 and SETD1A cause intellectual disability. Nat Genet, 44(5):551-553. doi: 10.1038/ng.2219
• Kleefstra syndrome. OMIM. Updated November 2017. Available from: https://omim.org/entry/610253
• Fryns JP, et al. (2009). Kleefstra syndrome in two mentally retarded girls with phenotypic findings in common with Coffin-Lowry syndrome. Genet Couns, 20(2):139-145. PMID: 19579898
• Kleefstra T, et al. (2006). Genotype-phenotype delineation of patients suspected of having 9q34 deletion syndrome. Eur J Hum Genet, 14(9): 1088-1098. doi: 10.1038/sj.ejhg.5201666
• Association for Kleefstra Syndrome: Support for Families Affected by Kleefstra Syndrome. Available from: https://www.kleefstrasyndrome.org/
• Kleefstra Syndrome Foundation. Available from: https://www.kleefstrasyndrome.org/
• PubMed. Available from: https://pubmed.ncbi.nlm.nih.gov/