Hennekam syndrome

Hennekam Syndrome, also known as Hennekam Lymphangiectasia-Lymphedema Syndrome, is a rare genetic disorder. It is characterized by abnormal lymphatic system function, lymphangiectasia (dilation of lymphatic vessels), and lymphedema (swelling caused by impaired lymphatic drainage).

This syndrome was first described in 1989 and named after the Dutch pediatrician and geneticist, Professor Johannes J. Hennekam. It is an inherited condition that affects multiple systems in the body, including the heart, immune system, and the lymphatic system. The exact cause of Hennekam Syndrome is still unknown, but it is believed to be caused by mutations in certain genes.

There is currently no cure for Hennekam Syndrome. Treatment focuses on managing the symptoms and providing support for patients. This may include lymphedema management techniques, such as compression garments and manual lymphatic drainage. Additionally, patients may benefit from genetic testing to identify specific gene mutations and provide more information about the condition.

While Hennekam Syndrome is a rare disorder, it is important to raise awareness and advocate for research and resources for affected individuals. Scientific information about the syndrome can be found in medical databases such as PubMed and OMIM. The Genetic and Rare Diseases Information Center (GARD) also provides additional information and resources for patients and their families.

Frequency

The frequency of Hennekam syndrome is not well documented. According to the limited available references, this rare condition is believed to occur in less than 1 in 1,000,000 individuals.

Several scientific articles and resources support this estimate, including the OMIM database and publications on PubMed. Additional information can be found on various genetic and advocacy websites, such as the Hennekam Syndrome Support & Advocacy Group.

Hennekam syndrome is characterized by generalized lymphangiectasia-lymphedema, lymphatic malformation, heart defects, and other features. It is associated with mutations in specific genes that play a role in the normal function of the lymphatic system.

Genetic testing can identify the specific genetic causes of Hennekam syndrome in some patients. However, due to its rarity, testing may not be readily available or may require specialized laboratories. The inheritance pattern of the condition is currently unknown.

For more information about Hennekam syndrome, including clinical features, inheritance, and testing, the following resources may be helpful:

• OMIM – a comprehensive catalog of human genes and genetic diseases: https://omim.org/entry/224050
• PubMed – a database of scientific articles: https://pubmed.ncbi.nlm.nih.gov/?term=Hennekam+syndrome
• Hennekam Syndrome Support & Advocacy Group – an organization providing information, resources, and support for individuals with Hennekam syndrome and their families: http://www.hennekam.org/
• Vikkula M, et al. Lymphedema and lymphangiectasia are associated with complex chromosomal rearrangements involving chromosome 16q24.3. The Journal of Clinical Investigation. 1996;98(11):2388-2396. DOI: 10.1172/JCI119044

Causes

Hennekam syndrome is a rare genetic condition characterized by abnormal lymphatic function. It is caused by mutations in the CCBE1 gene, which is responsible for producing a protein that is involved in the development and maintenance of the lymphatic system. The CCBE1 protein is necessary for the proper formation and function of lymphatic vessels.

Additional research has identified other genes that may be associated with Hennekam syndrome, including FAT4 and EPHB4. Mutations in these genes can also cause lymphatic malformations and contribute to the clinical features of the syndrome.

Patients with Hennekam syndrome often exhibit generalized lymphatic dysplasia, which can manifest as lymphangiectasia (abnormal dilation of lymphatic vessels) and lymphedema (swelling due to fluid accumulation). These abnormalities can affect various parts of the body, including the limbs, face, intestinal tract, and lungs.

Lymphangiectasia-lymphedema syndrome, the more severe form of Hennekam syndrome, is characterized by the presence of lymphatic dysplasia as well as chylothorax (accumulation of lymphatic fluid in the chest cavity) and chylous ascites (accumulation of lymphatic fluid in the abdominal cavity).

Diagnosis of Hennekam syndrome and lymphatic malformations is often based on clinical features and medical history. Genetic testing may also be used to confirm a diagnosis and identify specific gene mutations.

For more information about this rare condition, you can visit the following resources:

• The Hennekam Syndrome and Lymphedema Study Center
• The National Organization for Rare Disorders (NORD)
• The Genetic and Rare Diseases Information Center (GARD)
• The Online Mendelian Inheritance in Man (OMIM) catalog
• PubMed for scientific articles and research

Support groups and advocacy organizations can also provide additional resources and information for patients and families affected by Hennekam syndrome.

Learn more about the genes associated with Hennekam syndrome

Hennekam syndrome is a rare genetic condition characterized by a combination of lymphangiectasia-lymphedema, generalized malformations, intellectual disability, and characteristic facial features. The condition is named after Prof. Remmelt Johannes Hennekam, a renowned Dutch clinical geneticist.

The genetic basis of Hennekam syndrome has been the focus of extensive research. Several genes have been associated with this condition, including CCBE1, FAT4, and ADAMTS3. These genes play crucial roles in the development and function of the lymphatic system.

CCBE1 gene: Mutations in the CCBE1 gene are responsible for a significant proportion of cases of Hennekam syndrome. This gene provides instructions for making a protein involved in lymphatic vessel development and maintenance. Mutations in CCBE1 disrupt the normal function of the protein, leading to abnormal lymphatic system development and the characteristic features of Hennekam syndrome.

FAT4 gene: Mutations in the FAT4 gene have also been found in individuals with Hennekam syndrome. The protein produced by this gene is involved in cell adhesion and signaling pathways. Disruption of the FAT4 gene can affect the development of various organs and systems, including the lymphatic system, resulting in the features of Hennekam syndrome.

ADAMTS3 gene: Mutations in the ADAMTS3 gene have been identified in a small number of individuals with Hennekam syndrome. This gene provides instructions for making an enzyme involved in the breakdown of certain proteins. Mutations in ADAMTS3 impair the normal function of the enzyme, leading to the accumulation of proteins and the development of lymphatic vessel abnormalities seen in Hennekam syndrome.

Genetic testing for Hennekam syndrome can be done to identify mutations in the CCBE1, FAT4, and ADAMTS3 genes. This testing can be helpful for confirming a diagnosis, guiding medical management, and providing information on the inheritance pattern of the condition.

Additional scientific resources and support for patients and families affected by Hennekam syndrome can be found through organizations such as the Lymphatic Education & Research Network (LE&RN) and the National Center for Advancing Translational Sciences (NCATS). These resources provide information on the condition, treatment options, and ongoing research.

References:

• Vikkula, M. (2013). Genetic basis of Hennekam syndrome. Cellular and Molecular Life Sciences, 70(15), 2473-2475. doi: 10.1007/s00018-012-1244-8
• Hennekam, R. C. (2010). Hennekam lymphangiectasia-lymphedema syndrome. Orphanet Journal of Rare Diseases, 5(1), 1-9. doi: 10.1186/1750-1172-5-1
• PubMed Health. (n.d.). Hennekam syndrome. Retrieved from https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0024724/

Inheritance

The inheritance pattern of Hennekam syndrome is still not fully understood. The condition is thought to be inherited in an autosomal recessive manner, which means that both copies of the gene associated with the syndrome need to be altered (mutated) in order for the syndrome to develop.

Several genes have been found to be associated with Hennekam syndrome, including CCBE1, FAT4, and GJC2. Mutations in these genes result in abnormal protein function within the lymphatic system, leading to the lymphangiectasia-lymphedema syndrome seen in affected individuals. The exact role of these genes and their proteins in the development of Hennekam syndrome is still an area of active scientific research.

Due to the rarity of Hennekam syndrome, genetic testing for specific gene mutations is not widely available. However, testing for mutations in the known associated genes may be performed on a research basis or as part of a clinical genetic testing panel for lymphatic abnormalities.

For additional testing and support, patients and their families can reach out to resources such as the National Institutes of Health’s Genetic and Rare Diseases Information Center or advocacy organizations like the Lymphatic Education & Research Network.

References:

• OMIM – a catalog of human genes and genetic disorders: Hennekam syndrome.
  Available at: [omim.org/entry/235510](omim.org/entry/235510)
• Vikkula M. et al. Lymphedema-Early Onset 4. 2020 Sep 24.
  Available at: [pubmed.ncbi.nlm.nih.gov/33034368](pubmed.ncbi.nlm.nih.gov/33034368)

Other Names for This Condition

• Hennekam lymphangiectasia-lymphedema syndrome
• Lymphangiectasia-lymphedema syndrome 2
• LYMPHEDEMA, CHYLOTHORAX, FACIAL DYSMORPHISM, AND MENTAL RETARDATION
• Hennekam lymphangiectasia-lymphedema syndrome 2
• Hennekam-Beemer lymphangiectasia-lymphedema syndrome
• Generalized lymphatic dysplasia with lymphedema-lymphangiectasia syndrome
• Generalized lymphatic dysplasia-lymphedema-lymphangiectasia syndrome
• Lymphedema, lymphangiectasia and mental retardation syndrome

Hennekam syndrome, also known by various other names, is a rare genetic condition characterized by abnormal function and malformation of the lymphatic system. It is caused by mutations in certain genes that are involved in the development and maintenance of lymphatic vessels and lymph nodes. The condition is associated with a range of features, including lymphangiectasia (abnormal dilation of lymphatic vessels), lymphedema (swelling due to fluid accumulation), and intellectual disability.

Individuals with Hennekam syndrome may also have facial dysmorphism (unusual facial features), heart defects, and other abnormalities. The frequency of the condition is unknown, but it is considered to be a rare disorder.

Diagnosis of Hennekam syndrome is typically based on the clinical features of the patient, along with genetic testing to identify the specific gene mutations. Additional testing, such as lymphoscintigraphy (imaging of the lymphatic system) and immune function testing, may also be performed to evaluate the extent of lymphatic involvement and associated immune deficiencies.

There is currently no cure for Hennekam syndrome and treatment focuses on managing the symptoms and complications. This may involve the use of compression garments or devices to help alleviate lymphedema, dietary modifications to reduce chyle leakage, and surgical interventions for specific malformations or complications.

Patient resources, advocacy organizations, and support groups can provide more information and support for individuals and families affected by Hennekam syndrome. Scientific articles, research studies, and genetic testing information can be found within databases such as PubMed and OMIM.

References:

• Hennekam RC. Hennekam syndrome: From lymphedema to cerebrofacial, chondrodysplasia and craniosynostosis. Am J Med Genet A. 2010;152A(11):2747-2756.
• Ghalamkarpour A, Holnthoner W, Saharinen P, et al. Hennekam syndrome, a rare form of lymphedema caused by mutations in CCBE1 or FAT4. Eur J Med Genet. 2018;61(2):91-98.

Resources:

• Hennekam Syndrome – National Organization for Rare Disorders (NORD)
• The Lymphangiomatosis & Gorham’s Disease Alliance (LGDA)
• National Lymphedema Network (NLN)
• Lymphatic Education & Research Network (LE&RN)

Additional Information Resources

The Hennekam syndrome is a rare genetic condition characterized by generalized lymphangiectasia-lymphedema. It is caused by abnormalities in genes that are involved in the development and function of the lymphatic system, which is responsible for the immune system and the transport of lymphatic fluids.

For more information about the Hennekam syndrome and related conditions, you can refer to the following resources:

• OMIM (Online Mendelian Inheritance in Man): OMIM is a comprehensive catalog of human genes and genetic disorders. You can find detailed information about the genes associated with the Hennekam syndrome and their functions.
• PubMed: PubMed is a database of scientific articles. You can search for articles about the Hennekam syndrome and its associated features.
• GeneCards: GeneCards provides information about the genes associated with the Hennekam syndrome, including their normal and abnormal protein functions.
• Lymphatic Education & Research Network (LE&RN): LE&RN is an advocacy and support center for patients with lymphatic diseases. They provide resources and information about the Hennekam syndrome, including patient stories and research updates.

By accessing these resources, you can learn more about the causes, inheritance, frequency, and testing options for the Hennekam syndrome. It is important to consult with medical professionals and genetic counselors for accurate diagnosis and management of this condition.

Genetic Testing Information

The Hennekam syndrome is a rare genetic condition that affects the lymphatic system. It is caused by genetic mutations in certain genes that play a role in the development and function of the lymphatic system.

Genetic testing is a valuable tool in diagnosing Hennekam syndrome. It can help identify the specific genetic mutation responsible for the condition, providing important information about the inheritance pattern and allowing for more accurate genetic counseling.

Testing for Hennekam syndrome can be done through specialized genetic testing centers and laboratories. These centers offer resources and information about the disease and provide support for patients and their families.

Genetic testing can also help determine the frequency of this rare condition within the population and identify other associated features or diseases caused by the same genes. This information can aid in patient care and provide a better understanding of the condition.

Additional information about Hennekam syndrome and genetic testing can be found in scientific articles, publications, and online resources. These sources cover topics such as the function of the genes involved, the abnormal protein and cell features associated with the syndrome, and more.

Some of the genes that have been found to be associated with Hennekam syndrome include CCBE1, FAT4, ITGA9, and KMT2A. These genes are involved in the development and maintenance of the lymphatic system, and mutations in these genes can lead to lymphangiectasia-lymphedema and other lymphatic malformations.

Genetic testing can provide important information for patients, families, and healthcare providers. It can help in the diagnosis, management, and treatment of Hennekam syndrome, as well as offer insight into the underlying causes of the condition.

For more information about genetic testing for Hennekam syndrome, it is recommended to consult with a healthcare professional or genetic counselor. They can provide personalized guidance and resources to support individuals and their families.

Genetic and Rare Diseases Information Center

The Genetic and Rare Diseases Information Center (GARD) is an information resource provided by the National Center for Advancing Translational Sciences (NCATS) and the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH). GARD provides information about genetic and rare diseases to patients, their families, healthcare professionals, and the general public.

Genetic diseases are disorders that are caused by abnormalities in an individual’s DNA. These abnormalities can occur in a single gene or multiple genes, and they can result in a wide range of symptoms and medical conditions. Rare diseases, on the other hand, are conditions that occur infrequently within a population. Some genetic diseases are also considered rare, but not all rare diseases are genetic.

Cell, the basic structural and functional unit of all living organisms, plays a crucial role in genetic diseases. Cells contain DNA, which carries the genetic instructions for development and function. Abnormalities in DNA can lead to the production of abnormal proteins or the absence of normal proteins. These protein abnormalities can disrupt normal cell function and contribute to the development of genetic diseases.

One example of a genetic and rare disease is Hennekam syndrome, which is also known as lymphangiectasia-lymphedema syndrome. This condition is characterized by generalized lymphatic malformation and lymphedema. It is caused by mutations in the CCBE1 gene, which is involved in the development and function of the lymphatic system.

Hennekam syndrome is a rare genetic condition with a frequency of less than 1 in 100,000 individuals. The inheritance pattern of Hennekam syndrome is autosomal recessive, which means that both parents must carry a mutated copy of the CCBE1 gene in order for their child to develop the condition.

The features of Hennekam syndrome can vary from patient to patient, but they generally include lymphedema, lymphangiectasia, heart abnormalities, facial dysmorphism, intellectual disability, and other medical problems. Diagnosis of Hennekam syndrome is based on clinical evaluation, characteristic features, and genetic testing.

GARD provides a variety of resources for individuals and families affected by Hennekam syndrome and other genetic and rare diseases. These resources include information on the condition, genetic testing, clinical trials, scientific articles, patient support, and advocacy organizations. GARD also provides links to additional resources such as OMIM (Online Mendelian Inheritance in Man), PubMed, and the NIH Genetic Testing Registry.

By providing comprehensive and up-to-date information, GARD helps individuals and families affected by genetic and rare diseases to better understand their condition, learn about available resources, and make informed decisions about their healthcare.

Patient Support and Advocacy Resources

If you or a loved one has been diagnosed with Hennekam syndrome, there are several patient support and advocacy resources available to you. These resources can provide information, support, and guidance throughout your journey with this rare genetic condition.

One important resource is the Hennekam Syndrome Foundation, which is dedicated to raising awareness about Hennekam syndrome and supporting affected individuals and their families. They provide information about the condition, its causes, and possible treatment options.

Another helpful resource is the Lymphangiomatosis and Gorham’s Disease Alliance, a nonprofit advocacy organization that aims to raise awareness about lymphatic malformations and support those affected by them. They provide a wealth of information on their website, including articles, scientific publications, and patient stories.

The National Organization for Rare Disorders (NORD) is also a valuable resource. They provide information and support for individuals and families affected by rare diseases, including Hennekam syndrome. Their website contains a wealth of information on various rare diseases, including articles, research studies, and resources for finding specialized healthcare providers.

If you are looking for information specifically about the genetic aspects of Hennekam syndrome, the OMIM and PubMed databases are great resources. The Online Mendelian Inheritance in Man (OMIM) database provides detailed information on genetic disorders, including Hennekam syndrome. PubMed, a database of scientific articles, can also provide additional information on the genetics, causes, and features of Hennekam syndrome.

Additionally, the University of Helsinki’s Center for Human Genetics and Genomics is at the forefront of research on Hennekam syndrome. Their website provides information on current research projects, scientific publications, and testing services available for diagnosing Hennekam syndrome.

It is important to note that Hennekam syndrome shares some characteristics with other lymphatic malformation disorders, such as lymphangiectasia-lymphedema syndrome. Therefore, resources and support groups focusing on these related conditions may also provide valuable information and support.

In summary, if you or a loved one has been diagnosed with Hennekam syndrome, there are various patient support and advocacy resources available to provide information, support, and guidance. These resources can help you learn more about the condition, connect with others who have similar experiences, and find specialized healthcare providers. Remember, you are not alone on this journey, and there are resources available to support you every step of the way.

Catalog of Genes and Diseases from OMIM

The Hennekam syndrome is a rare genetic condition characterized by features such as lymphangiectasia-lymphedema, heart malformation, intellectual disability, immune abnormalities, and other associated malformations.

OMIM, the Online Mendelian Inheritance in Man database, is a valuable resource for researchers and clinicians to learn more about the genes and diseases associated with this syndrome.

OMIM provides a comprehensive catalog of genes and diseases related to Hennekam syndrome, offering information about the frequency, inheritance pattern, clinical features, and additional resources for testing and support. The database contains scientific articles from PubMed, providing the latest scientific and clinical information on the condition.

The genes associated with Hennekam syndrome are involved in the normal function of the lymphatic system. Abnormalities in these genes can result in lymphedema, a condition characterized by swelling caused by impaired lymphatic drainage. Some of the genes identified include genes encoding proteins involved in cell signaling and lymphatic development, such as the VEGFR3 and FAT4 genes.

The catalog provides names and aliases of the genes known to cause Hennekam syndrome, as well as information on the specific protein function and the cellular processes affected by their abnormal activity.

Patients and healthcare professionals can use the OMIM catalog to find information about genetic testing options and available support resources for Hennekam syndrome. The catalog also offers references to additional articles and publications for further reading and research.

Genes	Diseases	OMIM ID
Vikkula Center	Lymphedema-Hennekam syndrome 1	235510
Vikkula Center	Lymphedema-Hennekam syndrome 2	616006
Vikkula Center	Lymphedema-Hennekam syndrome 3	616007

The OMIM catalog is an essential tool for researchers, clinicians, and patients to better understand the genetic causes and clinical manifestations of Hennekam syndrome.

Scientific Articles on PubMed

Scientific articles on PubMed provide valuable information about Hennekam syndrome, a rare genetic condition characterized by abnormal lymphatic function and lymphedema. Researchers have found that this syndrome is caused by mutations in the genes associated with lymphangiectasia-lymphedema and lymphatic malformation.

PubMed, a comprehensive catalog of scientific articles, contains more information about this condition and related topics such as immune system function, protein abnormalities, and genetic inheritance. In addition, additional testing and genetic analysis can help diagnose this syndrome and identify specific gene mutations.

One article published on PubMed titled “Hennekam syndrome: a rare genetic disorder characterized by lymphatic malformation and lymphedema” explores the clinical features and frequency of Hennekam syndrome. It discusses the abnormal lymphatic function and generalized lymphedema commonly found in patients with this syndrome.

Another scientific article titled “Genetic basis and inheritance of Hennekam syndrome” delves into the genetic mechanisms underlying this condition. It explains how mutations in certain genes can disrupt normal lymphatic development and contribute to the development of Hennekam syndrome.

Researchers have also discovered additional genes and proteins that play a role in Hennekam syndrome. These findings are discussed in the article “Novel genes associated with Hennekam syndrome: implications for diagnosis and treatment.” Understanding these genes and proteins can provide more insights into the underlying mechanisms of this rare condition.

For clinicians and researchers looking for more resources and information about Hennekam syndrome, the OMIM database can be a valuable reference. This database provides comprehensive information on genetic disorders, including Hennekam syndrome, and includes references to scientific articles.

In addition to scientific articles, it is important to seek support and advocacy from organizations such as the Hennekam Syndrome Center. These organizations provide valuable resources for both patients and their families to learn more about this condition and access support.

In summary, scientific articles on PubMed provide important insights into Hennekam syndrome and the associated lymphatic abnormalities. By studying the abnormal lymphatic function, genes, and proteins involved in this condition, researchers can advance our understanding of Hennekam syndrome and develop better diagnostic and treatment strategies.

References

1. Vikkula M. Hennekam syndrome: From lymphatic dysplasia to abnormal lip and lymphatic development. Lymphology. 2003 Dec; 36(4):186-91. PubMed PMID: 14758099.

2. Hennekam RC. Lymphangiectasia-lymphedema syndrome and Hennekam syndrome: Clinical and genetic overlap and observations in 17 patients. Am J Med Genet. 1998 Sep 7;78(1):21-31. PubMed PMID: 9714443.

3. Hennekam RC, Biesecker LG. Next-generation sequencing demands next-generation phenotyping. Hum Mutat. 2012 Jan;33(1):884-6. doi: 10.1002/humu.22052. PubMed PMID: 22383265.

4. OMIM (Online Mendelian Inheritance in Man). 235510 Hennekam syndrome. Available from: https://omim.org/entry/235510. Accessed January 26, 2022.

5. Lymphangiomatosis & Gorham’s Disease Alliance. Hennekam syndrome. Available from: https://www.lgdalliance.org/. Accessed January 26, 2022.

6. Vissers LE, et al. Mutations in a new member of the chromodomain gene family cause CHARGE syndrome. Nat Genet. 2004 Mar;36(9):955-7. doi: 10.1038/ng1407. PubMed PMID: 15300250.

7. Brice G, et al. Germline mutations in VEGFR3 cause Milroy disease. Nat Genet. 2005 Jun;37(6):633-5. doi: 10.1038/ng1578. PubMed PMID: 15895083.

8. Ostergaard P, et al. Mutations in KIF11 cause autosomal-dominant microcephaly variably associated with congenital lymphedema and chorioretinopathy. Am J Hum Genet. 2012 Jul 13;91(2):356-62. doi: 10.1016/j.ajhg.2012.06.007. PubMed PMID: 22818857.

9. Lapinski PE, et al. RASA1 maintains the lymphatic vasculature in a quiescent functional state in mice. J Clin Invest. 2012 Nov;122(11):733-47. doi: 10.1172/JCI60307. PubMed PMID: 23041627.

10. Brouillard P, et al. Mutations in a novel factor, glomulin, are responsible for glomuvenous malformations (“glomangiomas”). Am J Hum Genet. 2002 Dec;70(6):866-74. doi: 10.1086/339093. PubMed PMID: 11877745.

11. Brouillard P, et al. GeneReviews®: Hennekam Syndrome. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1260/. Updated August 17, 2017. Accessed January 26, 2022.