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Disease Profile

Familial hyperaldosteronism type 2

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-5 / 10 000

33,100 - 165,500

US Estimated

1-5 / 10 000

51,350 - 256,750

Europe Estimated

Age of onset

Adult

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ICD-10

E26.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Familial hyperaldosteronism type II; Familial adrenal adenoma; FH2;

Categories

Congenital and Genetic Diseases; Endocrine Diseases; Rare Cancers

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
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Orpha Number: 404

Definition
Familial hyperaldosteronism type II (FH-II) is a heritable form of primary aldosteronism (PA) characterized by hypertension of varying severity, and non glucocticoid remediable hyperaldosteronism.

Epidemiology
PA is the most common form of secondary hypertension and is found in 10% of cases. However, familial forms are rare and represent 5% of adult PA cases. FH-II is considered the most common form of familial hyperaldosteronism and it is estimated at around 4% of all PA cases.

Clinical description
Hypertension, of varying severity even within members of the same family, is noted in most patients and occurs during adulthood. FH-II may present either as an aldosterone-producing adenoma (APA; see this term), bilateral adrenal hyperaldosteronism (BAH), or both. Fatigue, and muscle weakness are reported. Complications due to hypertension, chronic increase of aldosterone secretion accompanied with sodium retention and hypokalemia (found in approximately 25% of patients) may occur. In addition, patients with PA are at increased risk of cardiovascular events, such as coronary artery disease, stroke, non-fatal myocardial infarction, atrial fibrillation and heart failure.

Etiology
The exact etiopathogenetic mechanism is unknown. Linkage analysis has shown an association with the chromosomal region 7p22 but no causal gene has been found to date. Specific heterozygous missense mutations of the KCNJ5 gene (11q24), encoding the Gprotein-activated inward rectifier potassium channel GIRK-4 (p.G151E, p.Y152C) and causing FH type III (see this term), have been identified in some rare cases of families with a mild form of FH-III but that resembles FH-II.

Diagnostic methods
FH-II is diagnosed when PA is found in two or more family members by biochemical testing (aldosterone/ plasma renin activity (PRA) ratio testing, fludrocortisone or saline aldosterone suppression testing), and when diagnosis of familial hyperaldosteronism type I (FH-I; see this term) is excluded by hybrid gene testing. Patients show a non-specific variable aldosterone response to upright posture and AngII infusion. Adrenal venous sampling and imaging techniques (computed tomography, magnetic resonance imaging) allow to distinguish lateralized (APA, unilateral adrenal hyperplasia) from bilateral forms of the disease.

Differential diagnosis
FH-II is clinically and biochemically indistinguishable from sporadic PA. Differential diagnosis also includes the other forms of FH (FH-I and FH-III; see these terms).

Genetic counseling
FH-II is transmitted in an autosomal dominant mode with variable penetrance.

Management and treatment
FH-II does not respond to glucocorticoid treatment. Adrenalectomy is performed in case of APA, and medical therapy with aldosterone antagonists in case of BAH. In case of severe and/or resistant hypertension, additional antihypertensive medication is required.

Prognosis
With treatment prognosis is good. The cardiovascular morbidity of FH-II patients is increased compared to patients with essential hypertension.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
100% of people have these symptoms
Hypertension
0000822
80%-99% of people have these symptoms
Abnormal circulating renin
Abnormal plasma renin
0040084
Glucocortocoid-insensitive primary hyperaldosteronism
0011740
30%-79% of people have these symptoms
Secretory adrenocortical adenoma
0011746
5%-29% of people have these symptoms
Adrenal hyperplasia
Enlarged adrenal glands
0008221
Epistaxis
Bloody nose
Frequent nosebleeds
Nose bleed
Nose bleeding
Nosebleed

[ more ]

0000421
Headache
Headaches
0002315
Hypokalemia
Low blood potassium levels
0002900
Intracranial hemorrhage
Bleeding within the skull
0002170
Metabolic alkalosis
0200114
Muscle weakness
Muscular weakness
0001324
Nausea
0002018
Tinnitus
Ringing in ears
Ringing in the ears

[ more ]

0000360
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Incomplete penetrance
0003829
Variable expressivity
0003828

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Learn more

    These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

    In-Depth Information

    • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
    • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
    • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.