HALD2
MCID: HYP600
MIFTS: 30

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 57 72 29 13 6 70
Familial Hyperaldosteronism Type 2 20 58 70
Familial Hyperaldosteronism Type Ii 20 58
Familial Adrenal Adenoma 20 58
Hald2 57 72
Fh Ii 57 72
Fh-Ii 58 72
Fh2 20 58
Hyperaldosteronism Familial Type 2 73
Hyperaldosteronism, Familial, 2 72
Fhii 20

Characteristics:

Orphanet epidemiological data:

58
familial hyperaldosteronism type ii
Inheritance: Autosomal dominant; Age of onset: Adult; Age of death: elderly;

OMIM®:

57 (Updated 20-May-2021)
Miscellaneous:
variable expressivity
incomplete penetrance
de novo mutation (in some patients)
favorable response to spironolactone
early onset, usually before 20 years of age

Inheritance:
autosomal dominant


HPO:

31
hyperaldosteronism, familial, type ii:
Inheritance autosomal dominant inheritance
Onset and clinical course variable expressivity incomplete penetrance


Classifications:

Orphanet: 58  
Rare circulatory system diseases
Rare renal diseases
Rare endocrine diseases


External Ids:

OMIM® 57 605635
OMIM Phenotypic Series 57 PS103900
MeSH 44 D006929
ICD10 via Orphanet 33 E26.0
UMLS via Orphanet 71 C1854107
Orphanet 58 ORPHA404
MedGen 41 C1854107
UMLS 70 C1854107 C3839212

Summaries for Hyperaldosteronism, Familial, Type Ii

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. 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 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 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.

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). Related phenotypes are hypertension and glucocortocoid-insensitive primary hyperaldosteronism

OMIM® : 57 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) (Updated 20-May-2021)

UniProtKB/Swiss-Prot : 72 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 : 73 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
Rare Primary Hyperaldosteronism

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

(show all 11)
# Related Disease Score Top Affiliating Genes
1 familial hyperaldosteronism 29.0 FHII CLCN2
2 hyperaldosteronism, familial, type iii 11.1
3 conn's syndrome 10.4
4 retinoblastoma 10.2
5 adenoma 10.2
6 hyperaldosteronism, familial, type i 10.0
7 carney complex variant 10.0
8 adrenal cortical adenoma 10.0
9 aldosterone-producing adenoma 10.0
10 colorectal cancer 10.0
11 neuroblastoma 1 9.8

Graphical network of the top 20 diseases related to Hyperaldosteronism, Familial, Type Ii:



Diseases related to Hyperaldosteronism, Familial, Type Ii

Symptoms & Phenotypes for Hyperaldosteronism, Familial, Type Ii

Human phenotypes related to Hyperaldosteronism, Familial, Type Ii:

58 31 (show all 14)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertension 58 31 obligate (100%) Obligate (100%) HP:0000822
2 glucocortocoid-insensitive primary hyperaldosteronism 58 31 hallmark (90%) Very frequent (99-80%) HP:0011740
3 abnormal circulating renin 58 31 hallmark (90%) Very frequent (99-80%) HP:0040084
4 secretory adrenocortical adenoma 58 31 frequent (33%) Frequent (79-30%) HP:0011746
5 muscle weakness 58 31 occasional (7.5%) Occasional (29-5%) HP:0001324
6 hypokalemia 58 31 very rare (1%) Occasional (29-5%) HP:0002900
7 epistaxis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000421
8 intracranial hemorrhage 58 31 occasional (7.5%) Occasional (29-5%) HP:0002170
9 headache 58 31 occasional (7.5%) Occasional (29-5%) HP:0002315
10 tinnitus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000360
11 adrenal hyperplasia 58 31 occasional (7.5%) Occasional (29-5%) HP:0008221
12 nausea 58 31 occasional (7.5%) Occasional (29-5%) HP:0002018
13 metabolic alkalosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0200114
14 dexamethasone-suppresible primary hyperaldosteronism 58 Excluded (0%)

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Cardiovascular Vascular:
hypertension

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

Clinical features from OMIM®:

605635 (Updated 20-May-2021)

Drugs & Therapeutics for Hyperaldosteronism, Familial, Type Ii

Search Clinical Trials , 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 29 CLCN2

Anatomical Context for Hyperaldosteronism, Familial, Type Ii

Publications for Hyperaldosteronism, Familial, Type Ii

Articles related to Hyperaldosteronism, Familial, Type Ii:

# Title Authors PMID Year
1
CLCN2 chloride channel mutations in familial hyperaldosteronism type II. 57 6
29403011 2018
2
A gain-of-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism. 57 6
29403012 2018
3
Familial hyperaldosteronism type II: five families with a new variety of primary aldosteronism. 57 6
1521363 1992
4
A novel genetic locus for low renin hypertension: familial hyperaldosteronism type II maps to chromosome 7 (7p22). 57
11073536 2000
5
Familial hyperaldosteronism type II: description of a large kindred and exclusion of the aldosterone synthase (CYP11B2) gene. 57
9745430 1998
6
Hydrazone crosslinked hyaluronan-based hydrogels for therapeutic delivery of adipose stem cells to treat corneal defects. 61
29407158 2018

Variations for Hyperaldosteronism, Familial, Type Ii

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

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CLCN2 CLCN2, ARG172GLN Variation Pathogenic 559512 GRCh37:
GRCh38:
2 CLCN2 NM_004366.6(CLCN2):c.1084A>T (p.Lys362Ter) SNV Pathogenic 441167 rs1553856214 GRCh37: 3:184074782-184074782
GRCh38: 3:184356994-184356994
3 CLCN2 CLCN2, LYS362DEL Deletion Pathogenic 559516 GRCh37:
GRCh38:
4 CLCN2 NM_004366.6(CLCN2):c.2593A>C (p.Ser865Arg) SNV Pathogenic 441168 rs1553853557 GRCh37: 3:184064498-184064498
GRCh38: 3:184346710-184346710
5 CLCN2 NM_004366.6(CLCN2):c.65T>A (p.Met22Lys) SNV Pathogenic 441165 rs758379595 GRCh37: 3:184076918-184076918
GRCh38: 3:184359130-184359130
6 CLCN2 NM_004366.6(CLCN2):c.76T>A (p.Tyr26Asn) SNV Pathogenic 441166 rs1553857113 GRCh37: 3:184076907-184076907
GRCh38: 3:184359119-184359119
7 CLCN2 NM_004366.6(CLCN2):c.515G>A (p.Arg172Gln) SNV Pathogenic 441164 rs1293789661 GRCh37: 3:184075850-184075850
GRCh38: 3:184358062-184358062
8 CLCN2 NM_004366.6(CLCN2):c.71G>A (p.Gly24Asp) SNV Pathogenic 427066 rs1085307938 GRCh37: 3:184076912-184076912
GRCh38: 3:184359124-184359124
9 CLCN2 NM_004366.6(CLCN2):c.704G>A (p.Arg235Gln) SNV Uncertain significance 9038 rs71318369 GRCh37: 3:184075476-184075476
GRCh38: 3:184357688-184357688
10 CLCN2 NM_004366.6(CLCN2):c.1934G>A (p.Arg645Gln) SNV Uncertain significance 1028738 GRCh37: 3:184071132-184071132
GRCh38: 3:184353344-184353344

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

72
# Symbol AA change Variation ID SNP ID
1 CLCN2 p.Met22Lys VAR_081154 rs758379595
2 CLCN2 p.Gly24Asp VAR_081155 rs108530793
3 CLCN2 p.Tyr26Asn VAR_081156 rs155385711
4 CLCN2 p.Arg172Gln VAR_081157 rs129378966
5 CLCN2 p.Ser865Arg VAR_081159 rs155385355

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

Sources for Hyperaldosteronism, Familial, Type Ii

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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