HALD2
MCID: HYP600
MIFTS: 35

Hyperaldosteronism, Familial, Type Ii (HALD2)

Categories: Blood diseases, Cardiovascular diseases, Endocrine diseases, Genetic diseases, Nephrological diseases, Rare diseases

Aliases & Classifications for Hyperaldosteronism, Familial, Type Ii

MalaCards integrated aliases for Hyperaldosteronism, Familial, Type Ii:

Name: Hyperaldosteronism, Familial, Type Ii 58 76 30 13 6 74
Familial Hyperaldosteronism Type 2 54 60 74
Familial Hyperaldosteronism Type Ii 54 60
Familial Adrenal Adenoma 54 60
Hald2 58 76
Fh Ii 58 76
Fh-Ii 60 76
Fh2 54 60
Hyperaldosteronism Familial Type 2 77
Hyperaldosteronism, Familial, 2 76
Fhii 54

Characteristics:

Orphanet epidemiological data:

60
familial hyperaldosteronism type ii
Inheritance: Autosomal dominant; Age of onset: Adult; Age of death: elderly;

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
variable expressivity
incomplete penetrance
de novo mutation (in some patients)
favorable response to spironolactone
early onset, usually before 20 years of age


HPO:

33
hyperaldosteronism, familial, type ii:
Onset and clinical course variable expressivity incomplete penetrance


Classifications:

Orphanet: 60  
Rare endocrine diseases


External Ids:

OMIM 58 605635
MeSH 45 D006929
ICD10 via Orphanet 35 E26.0
UMLS via Orphanet 75 C1854107
Orphanet 60 ORPHA404
MedGen 43 C1854107

Summaries for Hyperaldosteronism, Familial, Type Ii

NIH Rare Diseases : 54 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 404Disease definitionFamilial hyperaldosteronism type II (FH-II) is a heritable form of primary aldosteronism (PA) characterized by hypertension of varying severity, and non glucocticoid remediable hyperaldosteronism.EpidemiologyPA 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 descriptionHypertension, 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.EtiologyThe 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 heterozygousmissense mutations of the KCNJ5 gene (11q24), encoding the G-protein-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 methodsFH-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 diagnosisFH-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 counselingFH-II is transmitted in an autosomal dominant mode with variable penetrance.Management and treatmentFH-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.PrognosisWith 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.

MalaCards based summary : Hyperaldosteronism, Familial, Type Ii, also known as familial hyperaldosteronism type 2, is related to familial hyperaldosteronism and hyperaldosteronism, familial, type iii. An important gene associated with Hyperaldosteronism, Familial, Type Ii is CLCN2 (Chloride Voltage-Gated Channel 2). The drugs Atorvastatin and Simvastatin have been mentioned in the context of this disorder. Affiliated tissues include testes, heart and adrenal gland, and related phenotypes are hypertension and abnormal circulating renin

OMIM : 58 Familial hyperaldosteronism type II is an autosomal dominant disorder characterized by hypertension due to increased aldosterone, often with hypokalemia. Patients usually present before age 20 years, although some may present in infancy. The disorder shows incomplete penetrance and variable expressivity; some patients may have normal blood pressure but have an increased aldosterone:renin ratio (ARR) on laboratory testing. Spironolactone is an effective treatment (summary by Scholl et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of familial hyperaldosteronism, see HALD1 (103900). (605635)

UniProtKB/Swiss-Prot : 76 Hyperaldosteronism, familial, 2: An autosomal dominant disorder characterized by elevated plasma aldosterone level and hypertension of varying severity even within members of the same family. Hypokalemia is observed in some patients. In HALD2, hypertension does not improve with glucocorticoid treatment.

Wikipedia : 77 Hyperaldosteronism is a medical condition wherein too much aldosterone is produced by the adrenal... more...

Related Diseases for Hyperaldosteronism, Familial, Type Ii

Diseases in the Familial Hyperaldosteronism family:

Hyperaldosteronism, Familial, Type I Hyperaldosteronism, Familial, Type Ii
Hyperaldosteronism, Familial, Type Iii Hyperaldosteronism, Familial, Type Iv

Diseases related to Hyperaldosteronism, Familial, Type Ii via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 familial hyperaldosteronism 29.0 CLCN2 FHII
2 hyperaldosteronism, familial, type iii 11.2
3 retinoblastoma 10.0

Symptoms & Phenotypes for Hyperaldosteronism, Familial, Type Ii

Human phenotypes related to Hyperaldosteronism, Familial, Type Ii:

60 33 (show all 14)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertension 60 33 obligate (100%) Obligate (100%) HP:0000822
2 abnormal circulating renin 60 33 hallmark (90%) Very frequent (99-80%) HP:0040084
3 glucocortocoid-insensitive primary hyperaldosteronism 60 33 hallmark (90%) Very frequent (99-80%) HP:0011740
4 secretory adrenocortical adenoma 60 33 frequent (33%) Frequent (79-30%) HP:0011746
5 muscle weakness 60 33 occasional (7.5%) Occasional (29-5%) HP:0001324
6 hypokalemia 60 33 very rare (1%) Occasional (29-5%) HP:0002900
7 headache 60 33 occasional (7.5%) Occasional (29-5%) HP:0002315
8 epistaxis 60 33 occasional (7.5%) Occasional (29-5%) HP:0000421
9 intracranial hemorrhage 60 33 occasional (7.5%) Occasional (29-5%) HP:0002170
10 tinnitus 60 33 occasional (7.5%) Occasional (29-5%) HP:0000360
11 nausea 60 33 occasional (7.5%) Occasional (29-5%) HP:0002018
12 adrenal hyperplasia 60 33 occasional (7.5%) Occasional (29-5%) HP:0008221
13 metabolic alkalosis 60 33 occasional (7.5%) Occasional (29-5%) HP:0200114
14 dexamethasone-suppresible primary hyperaldosteronism 60 Excluded (0%)

Symptoms via clinical synopsis from OMIM:

58
Cardiovascular Vascular:
hypertension

Laboratory Abnormalities:
hypokalemia (in some patients)
increased serum aldosterone
decreased renin
increased aldosterone:renin ratio

Clinical features from OMIM:

605635

Drugs & Therapeutics for Hyperaldosteronism, Familial, Type Ii

Drugs for Hyperaldosteronism, Familial, Type Ii (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 14)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Atorvastatin Approved Phase 3 134523-00-5 60823
2
Simvastatin Approved Phase 3 79902-63-9 54454
3
Calcium Approved, Nutraceutical Phase 3 7440-70-2 271
4 Calcium, Dietary Phase 3
5 Rosuvastatin Calcium Phase 3 147098-20-2
6 Hydroxymethylglutaryl-CoA Reductase Inhibitors Phase 3
7 Immunologic Factors Phase 3
8 Anticholesteremic Agents Phase 3
9 Antimetabolites Phase 3
10 Antibodies Phase 3
11 Antibodies, Monoclonal Phase 3
12 Hypolipidemic Agents Phase 3
13 Immunoglobulins Phase 3
14 Lipid Regulating Agents Phase 3

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Study of Alirocumab (REGN727/SAR236553) in Patients With heFH (Heterozygous Familial Hypercholesterolemia) Who Are Not Adequately Controlled With Their LMT (Lipid-Modifying Therapy) Completed NCT01709500 Phase 3 LMT (atorvastatin, simvastatin, or rosuvastatin);alirocumab;Placebo

Search NIH Clinical Center for Hyperaldosteronism, Familial, Type Ii

Genetic Tests for Hyperaldosteronism, Familial, Type Ii

Genetic tests related to Hyperaldosteronism, Familial, Type Ii:

# Genetic test Affiliating Genes
1 Hyperaldosteronism, Familial, Type Ii 30 CLCN2

Anatomical Context for Hyperaldosteronism, Familial, Type Ii

MalaCards organs/tissues related to Hyperaldosteronism, Familial, Type Ii:

42
Testes, Heart, Adrenal Gland

Publications for Hyperaldosteronism, Familial, Type Ii

Articles related to Hyperaldosteronism, Familial, Type Ii:

(show all 14)
# Title Authors Year
1
Pathogenesis of Familial Hyperaldosteronism Type II: New Concepts Involving Anion Channels. ( 30949771 )
2019
2
CLCN2 chloride channel mutations in familial hyperaldosteronism type II. ( 29403011 )
2018
3
A gain-of-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism. ( 29403012 )
2018
4
ARMC5 is not implicated in familial hyperaldosteronism type II (FH-II). ( 29022889 )
2017
5
Further study of chromosome 7p22 to identify the molecular basis of familial hyperaldosteronism type II. ( 20927129 )
2011
6
Examination of chromosome 7p22 candidate genes RBaK, PMS2 and GNA12 in familial hyperaldosteronism type II. ( 18307725 )
2008
7
Further evidence for linkage of familial hyperaldosteronism type II at chromosome 7p22 in Italian as well as Australian and South American families. ( 18622235 )
2008
8
No evidence for coding region mutations in the retinoblastoma-associated Kruppel-associated box protein gene (RBaK) causing familial hyperaldosteronism type II. ( 17121540 )
2006
9
Familial hyperaldosteronism type II is linked to the chromosome 7p22 region but also shows predicted heterogeneity. ( 16003173 )
2005
10
Genomic structure of the human gene for protein kinase A regulatory subunit R1-beta (PRKAR1B) on 7p22: no evidence for mutations in familial hyperaldosteronism type II in a large affected kindred. ( 15579186 )
2004
11
A novel genetic locus for low renin hypertension: familial hyperaldosteronism type II maps to chromosome 7 (7p22). ( 11073536 )
2000
12
Linkage analysis of familial hyperaldosteronism type II--absence of linkage to the gene encoding the angiotensin II receptor type 1. ( 9506777 )
1998
13
Familial hyperaldosteronism type II: description of a large kindred and exclusion of the aldosterone synthase (CYP11B2) gene. ( 9745430 )
1998
14
Familial hyperaldosteronism type II: five families with a new variety of primary aldosteronism. ( 1521363 )
1992

Variations for Hyperaldosteronism, Familial, Type Ii

UniProtKB/Swiss-Prot genetic disease variations for Hyperaldosteronism, Familial, Type Ii:

76
# Symbol AA change Variation ID SNP ID
1 CLCN2 p.Met22Lys VAR_081154
2 CLCN2 p.Gly24Asp VAR_081155 rs108530793
3 CLCN2 p.Tyr26Asn VAR_081156
4 CLCN2 p.Arg172Gln VAR_081157 rs129378966
5 CLCN2 p.Ser865Arg VAR_081159

ClinVar genetic disease variations for Hyperaldosteronism, Familial, Type Ii:

6 (show all 19)
# Gene Variation Type Significance SNP ID Assembly Location
1 CLCN2 NM_004366.5(CLCN2): c.704G> A (p.Arg235Gln) single nucleotide variant Uncertain significance rs71318369 GRCh37 Chromosome 3, 184075476: 184075476
2 CLCN2 NM_004366.5(CLCN2): c.704G> A (p.Arg235Gln) single nucleotide variant Uncertain significance rs71318369 GRCh38 Chromosome 3, 184357688: 184357688
3 CLCN2 NM_004366.4(CLCN2): c.71G> A (p.Gly24Asp) single nucleotide variant Pathogenic/Likely pathogenic rs1085307938 GRCh37 Chromosome 3, 184076912: 184076912
4 CLCN2 NM_004366.4(CLCN2): c.71G> A (p.Gly24Asp) single nucleotide variant Pathogenic/Likely pathogenic rs1085307938 GRCh38 Chromosome 3, 184359124: 184359124
5 CLCN2 NM_004366.5(CLCN2): c.2593A> C (p.Ser865Arg) single nucleotide variant Pathogenic rs1553853557 GRCh38 Chromosome 3, 184346710: 184346710
6 CLCN2 NM_004366.5(CLCN2): c.2593A> C (p.Ser865Arg) single nucleotide variant Pathogenic rs1553853557 GRCh37 Chromosome 3, 184064498: 184064498
7 CLCN2 NM_004366.5(CLCN2): c.1084A> T (p.Lys362del) single nucleotide variant Pathogenic rs1553856214 GRCh38 Chromosome 3, 184356994: 184356994
8 CLCN2 NM_004366.5(CLCN2): c.1084A> T (p.Lys362del) single nucleotide variant Pathogenic rs1553856214 GRCh37 Chromosome 3, 184074782: 184074782
9 CLCN2 NM_004366.5(CLCN2): c.515G> A (p.Arg172Gln) single nucleotide variant Pathogenic rs1293789661 GRCh37 Chromosome 3, 184075850: 184075850
10 CLCN2 NM_004366.5(CLCN2): c.515G> A (p.Arg172Gln) single nucleotide variant Pathogenic rs1293789661 GRCh38 Chromosome 3, 184358062: 184358062
11 CLCN2 NM_004366.5(CLCN2): c.76T> A (p.Tyr26Asn) single nucleotide variant Pathogenic rs1553857113 GRCh38 Chromosome 3, 184359119: 184359119
12 CLCN2 NM_004366.5(CLCN2): c.76T> A (p.Tyr26Asn) single nucleotide variant Pathogenic rs1553857113 GRCh37 Chromosome 3, 184076907: 184076907
13 CLCN2 NM_004366.5(CLCN2): c.65T> A (p.Met22Lys) single nucleotide variant Pathogenic rs758379595 GRCh38 Chromosome 3, 184359130: 184359130
14 CLCN2 NM_004366.5(CLCN2): c.65T> A (p.Met22Lys) single nucleotide variant Pathogenic rs758379595 GRCh37 Chromosome 3, 184076918: 184076918
15 CLCN2 CLCN2, SER865ARG undetermined variant Pathogenic
16 CLCN2 CLCN2, ARG172GLN undetermined variant Pathogenic
17 CLCN2 CLCN2, MET22LYS undetermined variant Pathogenic
18 CLCN2 CLCN2, TYR26ASN undetermined variant Pathogenic
19 CLCN2 CLCN2, LYS362DEL deletion Pathogenic

Expression for Hyperaldosteronism, Familial, Type Ii

Search GEO for disease gene expression data for Hyperaldosteronism, Familial, Type Ii.

Pathways for Hyperaldosteronism, Familial, Type Ii

GO Terms for Hyperaldosteronism, Familial, Type Ii

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