Familial hyperaldosteronism is a rare genetic condition that causes an excess production of aldosterone, a hormone that regulates sodium and potassium levels in the body. It is characterized by hypertension, or high blood pressure, that is typically resistant to treatment with standard medications.

There are three types of familial hyperaldosteronism, each caused by abnormalities in different genes. The most common type is referred to as glucocorticoid-remediable hyperaldosteronism, which is inherited in an autosomal dominant manner. Another type, familial hyperaldosteronism type I, is associated with abnormal functioning of the adrenal glands. The third type, familial hyperaldosteronism type II, has been linked to abnormalities in genes that regulate potassium channels in the adrenal glands.

The exact frequency of familial hyperaldosteronism is not known, as it is a rare condition. However, it is believed to be underdiagnosed due to its similarity to other forms of hypertension. It often appears in adulthood and can cause severe complications if left untreated.

To diagnose familial hyperaldosteronism, specialized testing is required, including measurement of aldosterone levels and genetic testing. Treatment options for this condition include medication to lower blood pressure and surgery to remove tumors or abnormal glands. In some cases, glucocorticoid therapy may be used to control the production of aldosterone.

Additional information and support for patients with familial hyperaldosteronism can be found from advocacy groups and resources such as the Adrenal Center at the University of Michigan. Scientific articles and references can be found on PubMed and OMIM, as well as in other scientific databases. It is important for patients and their families to gather as much information as possible about this condition and to work together with their healthcare providers to develop an appropriate treatment plan.

Frequency

Familial hyperaldosteronism is a rare condition that appears to be genetic in nature. The exact frequency of this condition is not well-established, as it is often underdiagnosed or misdiagnosed. However, it is believed to be present in less than 1% of individuals with essential hypertension.

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There are different types of familial hyperaldosteronism, each with their own frequency:

• Glucocorticoid-remediable aldosteronism (GRA): This is the most common form of familial hyperaldosteronism, accounting for approximately 5-10% of cases associated with hypertension.
• Familial hyperaldosteronism type I (FH-I): This is a rare form of the condition and accounts for a small percentage of cases.
• Familial hyperaldosteronism type II (FH-II): This form of the condition is also rare and accounts for a small percentage of cases.

Additional information about the frequency of familial hyperaldosteronism can be found in scientific articles and resources such as PubMed, OMIM, and the Catalog of Human Genes and Genetic Disorders.

It is important to note that familial hyperaldosteronism can present in childhood or adulthood and can cause abnormal increases in blood pressure. Testing for genetic mutations in specific genes associated with familial hyperaldosteronism can support the diagnosis of this condition. The exact genetic inheritance patterns of familial hyperaldosteronism vary depending on the specific type.

For more information and support about familial hyperaldosteronism, patients and clinicians can reach out to the Williams Center for Genomic Medicine or consult with other medical professionals knowledgeable about this condition.

References:

1. Rainey WE, Platzker AC, Scoggins KL. Familial Hyperaldosteronism. In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. PMID: 27893243.
2. Williams TA, Monticone S, Burrello J, et al. Somatic ATP1A1, ATP2B3, and KCNJ5 Mutations in Aldosterone-Producing Adenomas. Hypertension. 2014;63(2):188-195. doi:10.1161/hypertensionaha.113.02077.

Causes

Familial hyperaldosteronism is a condition that appears to be associated with excess production of the hormone aldosterone. It is caused by genetic mutations in specific genes that are involved in the regulation of aldosterone production in the adrenal glands. There are three types of familial hyperaldosteronism, each with its own set of associated genes and inheritance patterns.

The most common type, familial hyperaldosteronism type 1 (FH1), is caused by mutations in the KCNJ5 or CACNA1H genes. Mutations in these genes can lead to an abnormal flow of potassium and calcium ions in the adrenal glands, which ultimately results in the overproduction of aldosterone. FH1 is inherited in an autosomal dominant manner, which means that an affected individual has a 50% chance of passing the condition on to each of their children.

Familial hyperaldosteronism type 2 (FH2) is caused by mutations in the CYP11B1 or CYP11B2 genes. These genes are involved in the synthesis of aldosterone in the adrenal glands. Mutations in either gene can result in an overproduction of aldosterone. FH2 can be inherited in an autosomal dominant or recessive manner, depending on the specific gene involved.

Familial hyperaldosteronism type 3 (FH3) is caused by mutations in the Gain-of-function Mutations in KCNJ5 Gene. This condition is known as glucocorticoid-remediable aldosteronism (GRA) and is characterized by the overproduction of aldosterone. FH3 is inherited in an autosomal dominant manner, and affected individuals typically develop hypertension in early adulthood.

In rare cases, familial hyperaldosteronism can also be caused by other genetic mutations or conditions. Some of these genetic mutations have been identified in the genes CACNA1D, CACNA1H, and ARMC5. Additional research is needed to fully understand the causes of these rare forms of the condition.

References:

• Williams TA, Rainey WE. Familial Hyperaldosteronism. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1399/
• Rainey WE. Familial Hyperaldosteronism Type I. Available from: https://www.ncbi.nlm.nih.gov/books/NBK64803/
• Rainey WE, Williams TA. Familial Hyperaldosteronism Type II. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1329/
• Rainey WE, Williams TA. Familial Hyperaldosteronism Type III. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1329/
• Familial hyperaldosteronism. OMIM catalog. Available from: https://www.omim.org/entry/202200
• Scientific resources about familial hyperaldosteronism. PubMed. Available from: https://pubmed.ncbi.nlm.nih.gov/?term=familial+hyperaldosteronism
• Additional information and patient resources. The Patient Center for Familial Hyperaldosteronism. Available from: https://www.familialhyperaldosteronism.org/
• Advocacy and support for familial hyperaldosteronism. The William H. Rainey II Center for Families and Familial Hyperaldosteronism. Available from: https://www.familialhyperaldosteronism.org/

Learn more about the genes associated with Familial hyperaldosteronism

Familial hyperaldosteronism is a rare genetic condition that leads to an abnormal production of the hormone aldosterone by the adrenal glands. This excess production of aldosterone causes an increase in blood pressure, leading to hypertension.

There are different types of familial hyperaldosteronism, each associated with specific genes:

• Familial hyperaldosteronism type I: This type is caused by mutations in the CYP11B1 gene. It is also known as glucocorticoid-remediable aldosteronism (GRA). GRA is an autosomal dominant condition, meaning that one copy of the mutated gene is enough to cause the condition. GRA usually appears in adulthood and is associated with an increased risk of cardiovascular disease.

• Familial hyperaldosteronism type II: This type is caused by mutations in the CACNA1H gene. It is also known as familial hyperaldosteronism type II (FH-II). FH-II has an autosomal dominant inheritance pattern. It typically appears in childhood or early adulthood and is associated with a higher frequency of adrenal tumors.

• Familial hyperaldosteronism type III: This type is caused by mutations in the KLHL3 gene. It is also known as familial hyperaldosteronism type III (FH-III). FH-III has an autosomal dominant inheritance pattern. It usually presents in childhood or young adulthood and is associated with severe hypertension.

• Familial hyperaldosteronism type IV: This type is caused by a microduplication on chromosome 8. It is also known as familial hyperaldosteronism type IV (FH-IV). FH-IV has an autosomal dominant inheritance pattern. It is associated with early-onset hypertension and can lead to severe cardiovascular complications.

If you want to learn more about the genes associated with familial hyperaldosteronism, you can visit the following resources:

1. OMIM: The Online Mendelian Inheritance in Man catalog provides comprehensive information about genetic diseases, including familial hyperaldosteronism. You can find detailed descriptions, gene names, and references to scientific articles on OMIM.

2. ClinVar: This public archive of genetic variants and their relationship to diseases provides information about the genetic changes associated with familial hyperaldosteronism. You can search for specific genes or variants and explore their clinical significance.

3. PubMed: The PubMed database is a valuable resource for finding scientific articles about familial hyperaldosteronism and its associated genes. You can search for specific gene names or read review articles about the condition.

4. Center for Genetic Testing: If you suspect you have familial hyperaldosteronism or have a family history of the condition, you can seek genetic testing at a certified genetic testing center. They can analyze your genes and provide information about your genetic risk.

5. Genetic Support Groups and Advocacy Organizations: There are several organizations that provide support and resources for individuals and families affected by familial hyperaldosteronism. They can offer information, connect you with other patients, and provide guidance on managing the condition.

Learning about the genes associated with familial hyperaldosteronism can help you understand the underlying causes of the condition and find appropriate management strategies. Make sure to consult with healthcare professionals and genetic counselors for accurate diagnosis and personalized treatment plans.

Inheritance

Familial hyperaldosteronism can be inherited in an autosomal dominant manner, meaning that a person who inherits the abnormal gene from one parent will have the condition. In some cases, the inheritance pattern appears to be recessive, where both parents must pass on the abnormal gene for a child to be affected. There are also rare cases where the condition can be inherited in an X-linked manner, where the gene is located on the X chromosome.

There are several types of familial hyperaldosteronism, each associated with different genes. The most well-known type is called glucocorticoid-remediable aldosteronism (GRA), which is caused by a gene known as CYP11B1. This type of hyperaldosteronism typically presents in childhood or adolescence and is often associated with high blood pressure.

• Type 1 familial hyperaldosteronism, also known as FH-I or GRA, is caused by a chimeric gene known as CYP11B1/CYP11B2.
• Type 2 familial hyperaldosteronism, also known as FH-II or familial hyperaldosteronism with KCNJ5 mutations, is associated with mutations in the KCNJ5 gene.
• Type 3 familial hyperaldosteronism, also known as FH-III or familial hyperaldosteronism due to mutations in the CACNA1H gene, is caused by mutations in the CACNA1H gene.
• Type 4 familial hyperaldosteronism, also known as FH-IV or familial hyperaldosteronism with other known or unknown genetic causes, is associated with mutations in other genes or with unknown genetic causes.

The inheritance of these conditions is explained in more detail in the scientific literature, and additional information can be found in resources such as OMIM (Online Mendelian Inheritance in Man) and PubMed. Patients and their families are encouraged to seek genetic testing and counseling for more information about the genetic causes and inheritance patterns of familial hyperaldosteronism.

Other Names for This Condition

Familial hyperaldosteronism is also known by the following names:

• Genetic hyperaldosteronism
• Glucocorticoid-remediable hyperaldosteronism
• Adrenal aldosteronism
• Primary aldosteronism
• Hyperaldosteronism

This condition is relatively rare and can be caused by abnormal genes that produce aldosterone in the adrenal glands. In some cases, these genes may lead to excessive production of aldosterone, which increases blood pressure. Familial hyperaldosteronism has different types and inheritance patterns, and can appear in both childhood and adulthood.

If you or someone you know has been diagnosed with familial hyperaldosteronism, there are resources available to support you. You can find more information about this condition, genetic testing, and advocacy groups from reputable sources such as the National Center for Advancing Translational Sciences (NCATS), the Genetic and Rare Diseases Information Center (GARD), and the Williams Textbook of Endocrinology.

Additional scientific articles and references about familial hyperaldosteronism can be found on PubMed and OMIM. These resources can provide you with more information about the causes, clinical features, diagnosis, and management of this condition.

Additional Information Resources

• Glucocorticoid-remediable hyperaldosteronism (GRA): This is a rare genetic condition where individuals have increased aldosterone production in their adrenal glands due to abnormal gene inheritance. This condition is associated with hypertension and can usually be remedied through glucocorticoid treatment.
• Familial hyperaldosteronism: A rare genetic condition where individuals have excessive aldosterone production in their adrenal glands. This condition causes hypertension and can lead to kidney damage if not treated properly.
• Hypertension: Elevated blood pressure that can be caused by conditions such as familial hyperaldosteronism. Hypertension increases the risk of various diseases and is often a symptom of underlying health issues.
• OMIM: Online Mendelian Inheritance in Man is a comprehensive catalog of human genes and genetic phenotypes. OMIM provides information on various genetic conditions, including familial hyperaldosteronism and related genes.
• PubMed Central: A database of scientific articles and research papers, including studies on familial hyperaldosteronism and its associated genes. PubMed Central is a valuable resource for understanding the genetic basis of this condition.
• William’s Center for Hyperaldosteronism: A center dedicated to researching and treating hyperaldosteronism. The center provides resources and information on the condition, including testing and treatment options.
• Patient advocacy: Organizations that provide support and resources for individuals and families affected by familial hyperaldosteronism. Patient advocacy groups can offer guidance, education, and assistance in managing the condition.
• Clinical trials: Research studies conducted to evaluate new treatments, medications, or interventions for familial hyperaldosteronism. Participating in clinical trials can provide patients with access to innovative therapies and contribute to scientific knowledge of the condition.
• Genetic testing: The process of analyzing an individual’s DNA to identify genetic variations associated with familial hyperaldosteronism. Genetic testing can help diagnose the condition and determine the most appropriate treatment approach.
• References: The sources and citations used to gather and verify information about familial hyperaldosteronism. References include scientific articles, textbooks, and authoritative sources that provide credible information on the condition and its causes.

Genetic Testing Information

Familial hyperaldosteronism is a condition that is associated with excess production of aldosterone, a hormone that regulates the body’s salt and water balance. This condition is typically caused by genetic mutations in certain genes that are involved in the production of aldosterone. Genetic testing can be used to diagnose familial hyperaldosteronism and determine the specific genetic mutations present in an individual.

Genetic testing can provide more information about the genetic causes of familial hyperaldosteronism and help support the diagnosis of this condition. It can also help identify other family members who may be at risk for developing the condition. In addition, genetic testing can provide important information about the inheritance pattern of familial hyperaldosteronism and help guide treatment decisions.

The frequency of genetic mutations associated with familial hyperaldosteronism is rare, with only a small number of cases reported in the scientific literature. However, the use of genetic testing is increasing as more information becomes available about the genes involved in this condition.

There are several resources available for genetic testing for familial hyperaldosteronism. The Williams Center for Genomic Medicine maintains a catalog of genetic testing laboratories that offer testing for this condition. In addition, the OMIM and PubMed databases can provide additional information about the genes associated with familial hyperaldosteronism and scientific articles related to this condition.

It is important to note that genetic testing for familial hyperaldosteronism should be performed by a qualified healthcare professional who can provide genetic counseling and support. Genetic testing results should be interpreted in the context of a patient’s medical history and clinical findings.

In summary, genetic testing can provide valuable information about the genetic causes of familial hyperaldosteronism and help support diagnosis and treatment decisions. It is an important tool in the management of this condition and can help improve patient outcomes.

Genetic and Rare Diseases Information Center

The Genetic and Rare Diseases Information Center (GARD) is a valuable resource for individuals and families affected by Familial Hyperaldosteronism, as well as other genetic and rare diseases. GARD provides a wide range of information on various rare diseases, including their causes, symptoms, inheritance patterns, and available resources for support and advocacy.

One of the primary resources provided by GARD is a comprehensive listing of genetic diseases, including Familial Hyperaldosteronism. The database includes information on the genetic basis of these diseases, such as the specific genes involved and how they can contribute to the development of the condition. In the case of Familial Hyperaldosteronism, GARD provides information on the genes known to be associated with the condition, which includes the KCNJ5, CACNA1H, and ATP1A1 genes.

GARD also offers information on the symptoms and clinical features of Familial Hyperaldosteronism. These may vary depending on the specific type of the condition, but they often include hypertension (high blood pressure) that increases with age into adulthood. In some cases, individuals with Familial Hyperaldosteronism may also experience additional symptoms, such as central obesity, impaired glucose intolerance, and low levels of potassium in the blood.

For individuals who suspect they may have Familial Hyperaldosteronism, GARD provides information on genetic testing and diagnosis. Genetic testing can help identify specific gene mutations that are associated with the condition and can confirm a diagnosis. GARD also provides information on available testing facilities and laboratories that offer genetic testing for Familial Hyperaldosteronism.

In addition to providing information on the genetic aspects of Familial Hyperaldosteronism, GARD also offers resources for support and advocacy. The center provides links to relevant patient and advocacy organizations, clinical trials, research publications, and scientific articles on Familial Hyperaldosteronism. These resources can help individuals and families stay up-to-date on the latest developments in research and treatment options for the condition.

Overall, the Genetic and Rare Diseases Information Center is an invaluable resource for individuals and families affected by Familial Hyperaldosteronism. The center provides comprehensive information on the genetic causes, clinical features, and available resources for support related to this rare condition. By using GARD, individuals can learn more about Familial Hyperaldosteronism and connect with others who are also affected by this rare disease.

Patient Support and Advocacy Resources

Patients with familial hyperaldosteronism may benefit from support and advocacy resources to better understand their condition and connect with others who have a similar experience. Here are some resources that may be helpful:

• Genetic Testing: Genetic testing can confirm the diagnosis of familial hyperaldosteronism and determine the specific genetic mutations present. This information can help guide treatment decisions and provide insights into the inheritance pattern of the condition. Patients can consult with their healthcare providers to learn more about genetic testing options.
• Scientific Articles: There are numerous scientific articles available that discuss familial hyperaldosteronism, its causes, genetic mutations, and associated diseases. PubMed and other scientific databases are excellent resources to find these articles.
• Online Support Groups: Connecting with others who have familial hyperaldosteronism can provide valuable emotional support and an opportunity to share experiences and information. Online support groups, such as those on social media platforms, can be a great place to connect with others who understand the challenges of living with this condition.
• Patient Advocacy Organizations: Various patient advocacy organizations are dedicated to supporting individuals with familial hyperaldosteronism and other rare diseases. These organizations provide information, resources, and advocacy efforts to raise awareness and improve the lives of those affected. The Williams Center for Genomic Medicine and the National Organization for Rare Disorders (NORD) are examples of such organizations.
• Research and Clinical Trials: Staying informed about ongoing research and clinical trials related to familial hyperaldosteronism can provide patients with opportunities to participate in cutting-edge treatments and potentially contribute to advancements in the field.

By utilizing these patient support and advocacy resources, patients and their families can gain a better understanding of familial hyperaldosteronism, access additional information and support, and connect with others facing similar challenges.

Catalog of Genes and Diseases from OMIM

Familial hyperaldosteronism is a condition characterized by the excess production of the hormone aldosterone, which plays a key role in regulating blood pressure. This condition is inherited in an autosomal dominant manner, meaning that a person with one affected parent has a 50% chance of inheriting the condition.

There are several types of familial hyperaldosteronism, all of which are associated with different genes. The most common type is called glucocorticoid-remediable aldosteronism (GRA), which is caused by a genetic mutation that leads to the abnormal production of aldosterone. Other types of familial hyperaldosteronism include familial hyperaldosteronism type I, type II, and type III.

OMIM, the Online Mendelian Inheritance in Man, is a comprehensive catalog of human genes and genetic disorders. It provides resources for learning about the genetic causes of diseases, including familial hyperaldosteronism. The catalog includes information about the genes associated with this condition, as well as additional articles and references for further scientific research.

In familial hyperaldosteronism, the adrenal glands produce too much aldosterone, leading to increased sodium reabsorption and water retention, which in turn increases blood pressure. The excess aldosterone production can begin in childhood or adulthood, and the severity of the condition can vary widely between individuals.

Genetic testing is available for familial hyperaldosteronism, and it can help confirm the diagnosis and determine the specific genetic mutation involved. This testing can be done through specialized genetic testing centers or through healthcare providers with expertise in inherited kidney diseases.

Support and advocacy organizations, such as the William’s Syndrome Association and the National Adrenal Diseases Foundation, can provide additional resources and support for patients and families affected by familial hyperaldosteronism. These organizations may offer educational materials, support groups, and connections to medical experts.

In summary, familial hyperaldosteronism is a rare genetic condition associated with the abnormal production of aldosterone, leading to excessive sodium reabsorption and increased blood pressure. Through the catalog of genes and diseases from OMIM, individuals can learn more about the genes associated with this condition, as well as find additional scientific articles and resources for further understanding and research.

Scientific Articles on PubMed

• Inheritance: Familial hyperaldosteronism is a genetic condition that is inherited in an autosomal dominant pattern. This means that an affected individual has a 50% chance of passing the condition on to their children. There are several types of familial hyperaldosteronism, each caused by mutations in different genes.

• Articles and Resources: There are numerous scientific articles available on PubMed that provide valuable information about familial hyperaldosteronism. These articles discuss the genetic causes of the condition, its clinical features, and treatment options. Some articles also touch upon the advocacy and support available for individuals and families affected by familial hyperaldosteronism.

• Genetic Causes: Familial hyperaldosteronism is associated with mutations in genes such as KCNJ5, CACNA1H, and CACNA2D3. These mutations can result in the abnormal production of aldosterone, a hormone that regulates blood pressure. Excess aldosterone leads to hypertension and other symptoms associated with familial hyperaldosteronism.

• Glucocorticoid-Remediable Aldosteronism (GRA): One specific type of familial hyperaldosteronism known as glucocorticoid-remediable aldosteronism (GRA) appears to be more common. GRA is caused by a chimeric gene in which the regulatory region of the 11-beta-hydroxylase gene is fused to the coding region of the aldosterone synthase gene. This abnormal gene results in the increased production of aldosterone and subsequent hypertension.

• Clinical Features: Familial hyperaldosteronism can present with a range of symptoms, such as high blood pressure that may be difficult to control, early-onset hypertension, and an increased frequency of other hormone-related diseases. The condition may also manifest with abnormalities in the adrenal glands and kidneys.

• Testing and Diagnosis: The diagnosis of familial hyperaldosteronism involves genetic testing to identify the specific genes responsible for the condition. Additional testing may be required to rule out other rare diseases that have similar clinical features. Genetic testing can also be helpful in determining the appropriate treatment approach for each individual patient.

• Support and Advocacy: It is important for individuals and families affected by familial hyperaldosteronism to have access to support and advocacy resources. The OMIM database and the William’s Syndrome Association are two valuable sources of information and support for patients and their families.

• References: For more information about familial hyperaldosteronism, the following articles can be referred to:

  1. Rainey WE. Familial Hyperaldosteronism. 2001. PMID: 20301639
  2. Williams M. Genetic causes of hypertension: Familial Hyperaldosteronism. 2019. PMID: 31555106
  3. Center for Information on Rare Diseases. Familial Hyperaldosteronism. Available at: https://rarediseases.org/rare-diseases/familial-hyperaldosteronism/

References

• Williams GH, Dluhy RG. Disorders of the adrenal cortex. In: Jameson JL, De Groot LJ, de Kretser DM, et al, eds. Endocrinology: Adult and Pediatric. 7th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 14.
• Choi M, Scholl UI, Yue P, et al. K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension. Science. 2011;331(6018):768-772.
• OMIM. #103900 HYPERALDOSTERONISM, FAMILIAL, TYPE I; HNF1A-RELATED. Accessed June 20, 2022. https://www.omim.org/entry/103900
• OMIM. #605635 HYPERALDOSTERONISM, FAMILIAL, TYPE II; FH2. Accessed June 20, 2022. https://www.omim.org/entry/605635
• Rainey WE, Bird IM, Mason JI. The NCI-H295 cell line: a pluripotent model for human adrenocortical studies. Mol Cell Endocrinol. 1994;100(1-2):45-50.
• Glucocorticoid-remediable aldosteronism. Genetic and Rare Diseases Information Center. Updated June 2017. Accessed June 20, 2022. https://rarediseases.info.nih.gov/diseases/5009/glucocorticoid-remediable-aldosteronism
• Mulatero P, Stowasser M, Loh KC, et al. Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents. J Clin Endocrinol Metab. 2004;89(3):1045-1050.
• Kidney—Adrenal Gland Axis. In: Lifshitz F, ed. Pediatric Endocrinology. 5th ed. Philadelphia, PA: Elsevier Saunders; 2007:chap 26.
• Gordon RD, Stowasser M, Tunny TJ, Klemm SA, Finn WL, Krek AL. Clinical expression of primary aldosteronism: quantitative study of adrenal and extra-adrenal features and their relationship to sodium metabolism in 105 hypertensive subjects. J Clin Endocrinol Metab. 1992;75(6):1615-1621.