FH
MCID: FML156
MIFTS: 41

Familial Hyperaldosteronism (FH)

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

Aliases & Classifications for Familial Hyperaldosteronism

MalaCards integrated aliases for Familial Hyperaldosteronism:

Name: Familial Hyperaldosteronism 25 59 29 6 72
Fh 25 59
Familial Primary Aldosteronism 25
Hyperaldosteronism, Familial 25
Hereditary Aldosteronism 25

Characteristics:

Orphanet epidemiological data:

59
familial hyperaldosteronism
Inheritance: Autosomal dominant; Age of onset: All ages;

Classifications:

Orphanet: 59  
Rare endocrine diseases


External Ids:

ICD10 via Orphanet 34 E26.0
UMLS via Orphanet 73 C3713420
Orphanet 59 ORPHA235936
UMLS 72 C3713420

Summaries for Familial Hyperaldosteronism

Genetics Home Reference : 25 Familial hyperaldosteronism is a group of inherited conditions in which the adrenal glands, which are small glands located on top of each kidney, produce too much of the hormone aldosterone. Aldosterone helps control the amount of salt retained by the kidneys. Excess aldosterone causes the kidneys to retain more salt than normal, which in turn increases the body's fluid levels and blood pressure. People with familial hyperaldosteronism may develop severe high blood pressure (hypertension), often early in life. Without treatment, hypertension increases the risk of strokes, heart attacks, and kidney failure. Familial hyperaldosteronism is categorized into three types, distinguished by their clinical features and genetic causes. In familial hyperaldosteronism type I, hypertension generally appears in childhood to early adulthood and can range from mild to severe. This type can be treated with steroid medications called glucocorticoids, so it is also known as glucocorticoid-remediable aldosteronism (GRA). In familial hyperaldosteronism type II, hypertension usually appears in early to middle adulthood and does not improve with glucocorticoid treatment. In most individuals with familial hyperaldosteronism type III, the adrenal glands are enlarged up to six times their normal size. These affected individuals have severe hypertension that starts in childhood. The hypertension is difficult to treat and often results in damage to organs such as the heart and kidneys. Rarely, individuals with type III have milder symptoms with treatable hypertension and no adrenal gland enlargement. There are other forms of hyperaldosteronism that are not familial. These conditions are caused by various problems in the adrenal glands or kidneys. In some cases, a cause for the increase in aldosterone levels cannot be found.

MalaCards based summary : Familial Hyperaldosteronism, also known as fh, is related to hyperaldosteronism, familial, type i and hyperaldosteronism, familial, type ii. An important gene associated with Familial Hyperaldosteronism is KCNJ5 (Potassium Inwardly Rectifying Channel Subfamily J Member 5), and among its related pathways/superpathways are Aldosterone synthesis and secretion and superpathway of steroid hormone biosynthesis. Affiliated tissues include heart, kidney and adrenal gland, and related phenotypes are cardiovascular system and endocrine/exocrine gland

Related Diseases for Familial Hyperaldosteronism

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 Familial Hyperaldosteronism via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 179)
# Related Disease Score Top Affiliating Genes
1 hyperaldosteronism, familial, type i 34.2 CYP11B2 CYP11B1
2 hyperaldosteronism, familial, type ii 33.8 FHII CLCN2
3 cell type benign neoplasm 31.7 MEN1 KCNJ5 CYP11B2
4 hypertension, essential 31.1 MEN1 CYP11B2 CYP11B1 AGTR1
5 conn's syndrome 31.0 MEN1 KCNJ5 CYP11B2 CYP11B1 CACNA1H AGTR1
6 aldosterone-producing adenoma 30.9 KCNJ5 CYP11B2
7 adenoma 30.3 MEN1 KCNJ5 CYP11B2
8 adrenal adenoma 29.5 MEN1 KCNJ5 CYP11B2 CYP11B1
9 fumarase deficiency 12.3
10 hereditary leiomyomatosis and renal cell cancer 12.3
11 renal cell carcinoma, nonpapillary 12.1
12 leiomyoma, uterine 12.1
13 hyperaldosteronism, familial, type iii 12.1
14 floating-harbor syndrome 12.0
15 renal cell carcinoma, papillary, 1 11.9
16 hypercholesterolemia, familial, 1 11.9
17 familial hypercholesterolemia 11.8
18 inherited cancer-predisposing syndrome 11.8
19 leiomyomatosis 11.8
20 leiomyoma 11.7
21 leiomyosarcoma 11.7
22 kidney cancer 11.7
23 paraganglioma 11.7
24 myoma 11.7
25 pheochromocytoma 11.6
26 leiomyoma cutis 11.6
27 hyperaldosteronism, familial, type iv 11.6
28 fumarate hydratase deficiency 11.5
29 hereditary paraganglioma-pheochromocytoma syndromes 11.4
30 encephalopathy 11.3
31 hypercholesterolemia, familial, 4 11.3
32 asperger syndrome 11.3
33 cutaneous leiomyosarcoma 11.3
34 birt-hogg-dube syndrome 11.2
35 deafness, autosomal dominant 69 11.2
36 carrion's disease 11.2
37 reproductive organ benign neoplasm 11.2
38 uterine benign neoplasm 11.2
39 peritoneal benign neoplasm 11.2
40 gastric leiomyoma 11.2
41 xanthogranulomatous pyelonephritis 11.2
42 dermis tumor 11.2
43 cystic kidney disease 11.2
44 skin benign neoplasm 11.2
45 mucinous ovarian cystadenoma 11.2
46 ovarian cystadenoma 11.2
47 hereditary renal cell carcinoma 11.2
48 dartoic leiomyoma 11.2
49 diffuse peritoneal leiomyomatosis 11.2
50 familial renal papillary carcinoma 11.2

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



Diseases related to Familial Hyperaldosteronism

Symptoms & Phenotypes for Familial Hyperaldosteronism

MGI Mouse Phenotypes related to Familial Hyperaldosteronism:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.56 AGTR1 CACNA1H CLCN2 CYP11B1 CYP11B2 GNA12
2 endocrine/exocrine gland MP:0005379 9.17 ARMC5 CLCN2 CYP11B1 CYP11B2 GNA12 MEN1

Drugs & Therapeutics for Familial Hyperaldosteronism

Search Clinical Trials , NIH Clinical Center for Familial Hyperaldosteronism

Genetic Tests for Familial Hyperaldosteronism

Genetic tests related to Familial Hyperaldosteronism:

# Genetic test Affiliating Genes
1 Familial Hyperaldosteronism 29

Anatomical Context for Familial Hyperaldosteronism

MalaCards organs/tissues related to Familial Hyperaldosteronism:

41
Heart, Kidney, Adrenal Gland, Testes, Endothelial

Publications for Familial Hyperaldosteronism

Articles related to Familial Hyperaldosteronism:

(show top 50) (show all 128)
# Title Authors PMID Year
1
Molecular mechanisms in primary aldosteronism 38
31397984 2019
2
Adrenalectomy completely cured hypertension in familial hyperaldosteronism type I patients with somatic KCNJ5 mutation. 38
31287546 2019
3
Primary aldosteronism associated with a germline variant in CACNA1H. 38
31126930 2019
4
Pathogenesis of Familial Hyperaldosteronism Type II: New Concepts Involving Anion Channels. 38
30949771 2019
5
Familial hyperaldosteronism type III a novel case and review of literature. 38
30569443 2019
6
Inherited Forms of Primary Hyperaldosteronism: New Genes, New Phenotypes and Proposition of A New Classification. 38
30199917 2019
7
Genetic aspects of primary hyperaldosteronism. 38
29938936 2018
8
Saga of Familial Hyperaldosteronism: Yet a New Channel. 38
29735637 2018
9
Overview of aldosterone-related genetic syndromes and recent advances. 38
29432258 2018
10
Comparative Genomics and Transcriptome Profiling in Primary Aldosteronism. 38
29642543 2018
11
CLCN2 chloride channel mutations in familial hyperaldosteronism type II. 38
29403011 2018
12
GENETICS IN ENDOCRINOLOGY: The expanding genetic horizon of primary aldosteronism. 38
29348113 2018
13
DIAGNOSIS OF ENDOCRINE DISEASE: 18-Oxocortisol and 18-hydroxycortisol: is there clinical utility of these steroids? 38
28904009 2018
14
Familial hyperaldosteronism type III. 38
28447626 2017
15
Unanswered Questions in the Genetic Basis of Primary Aldosteronism. 38
29065434 2017
16
ARMC5 is not implicated in familial hyperaldosteronism type II (FH-II). 38
29022889 2017
17
Genetic disorders in primary aldosteronism-familial and somatic. 38
27013018 2017
18
Disordered zonal and cellular CYP11B2 enzyme expression in familial hyperaldosteronism type 3. 38
27793677 2017
19
Functional characterization of two novel germline mutations of the KCNJ5 gene in hypertensive patients without primary aldosteronism but with ACTH-dependent aldosterone hypersecretion. 38
27293068 2016
20
Evaluation of a Recently Established Test for Familial Hyperaldosteronism Type 1. 38
27923252 2016
21
CACNA1H Mutations Are Associated With Different Forms of Primary Aldosteronism. 38
27729216 2016
22
A Novel Phenotype of Familial Hyperaldosteronism Type III: Concurrence of Aldosteronism and Cushing's Syndrome. 38
27403928 2016
23
Genetics of primary hyperaldosteronism. 38
27485459 2016
24
Prospective validation of an automated chemiluminescence-based assay of renin and aldosterone for the work-up of arterial hypertension. 38
26824982 2016
25
SFE/SFHTA/AFCE consensus on primary aldosteronism, part 4: Subtype diagnosis. 38
27036860 2016
26
SFE/SFHTA/AFCE consensus on primary aldosteronism, part 5: Genetic diagnosis of primary aldosteronism. 38
27315758 2016
27
Mutated KCNJ5 activates the acute and chronic regulatory steps in aldosterone production. 38
27099398 2016
28
Recent Developments in Primary Aldosteronism. 38
27219889 2016
29
Hyperplasia in glands with hormone excess. 38
26407873 2016
30
An Update on Familial Hyperaldosteronism. 38
26445452 2015
31
Bilateral Idiopathic Adrenal Hyperplasia: Genetics and Beyond. 38
26610199 2015
32
The molecular basis of primary aldosteronism: from chimeric gene to channelopathy. 38
25555247 2015
33
Genetics of primary aldosteronism. 38
25667376 2015
34
An update on novel mechanisms of primary aldosteronism. 38
25424518 2015
35
Pregnancy normalized familial hyperaldosteronism type I: a novel role for progesterone? 38
24943290 2015
36
A case of severe hyperaldosteronism caused by a de novo mutation affecting a critical salt bridge Kir3.4 residue. 38
25322277 2015
37
Understanding primary aldosteronism: impact of next generation sequencing and expression profiling. 38
25240470 2015
38
Channelopathies. 38
24578711 2014
39
Discordant genotype-phenotype correlation in familial hyperaldosteronism type III with KCNJ5 gene mutation: a patient report and review of the literature. 38
24819081 2014
40
Minireview: potassium channels and aldosterone dysregulation: is primary aldosteronism a potassium channelopathy? 38
24248457 2014
41
Genetics of primary aldosteronism. 38
24943299 2014
42
Overview of the genetic determinants of primary aldosteronism. 38
24817817 2014
43
Gene mutations that promote adrenal aldosterone production, sodium retention, and hypertension. 38
24399884 2013
44
a Novel Y152C KCNJ5 mutation responsible for familial hyperaldosteronism type III. 38
24037882 2013
45
[Primary hyperaldosteronism by unilateral adrenal hyperplasia: a report of two cases]. 38
24276190 2013
46
Different effects of progesterone and estradiol on chimeric and wild type aldosterone synthase in vitro. 38
23938178 2013
47
Genetics of mineralocorticoid excess: an update for clinicians. 38
23610123 2013
48
The renaissance of primary aldosteronism: what has it taught us? 38
23402683 2013
49
Role of KCNJ5 in familial and sporadic primary aldosteronism. 38
23229280 2013
50
Genetic variations in the KCNJ5 gene in primary aldosteronism patients from Xinjiang, China. 38
23382865 2013

Variations for Familial Hyperaldosteronism

ClinVar genetic disease variations for Familial Hyperaldosteronism:

6 (show top 50) (show all 98)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 KCNJ5 NM_000890.5(KCNJ5): c.1159G> C (p.Gly387Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs199830292 11:128786525-128786525 11:128916630-128916630
2 KCNJ5 NM_000890.5(KCNJ5): c.591G> A (p.Ala197=) single nucleotide variant Conflicting interpretations of pathogenicity rs750048771 11:128781759-128781759 11:128911864-128911864
3 KCNJ5 NM_000890.5(KCNJ5): c.-333_-332CA[24] short repeat Uncertain significance rs113761140 11:128761334-128761337 11:128891439-128891442
4 KCNJ5 NM_000890.5(KCNJ5): c.-293_-288del deletion Uncertain significance rs886047997 11:128761334-128761339 11:128891439-128891444
5 KCNJ5 NM_000890.5(KCNJ5): c.-291_-290GA[3] short repeat Uncertain significance rs886048000 11:128761335-128761336 11:128891440-128891441
6 KCNJ5 NM_000890.5(KCNJ5): c.-287G> C single nucleotide variant Uncertain significance rs868130049 11:128761340-128761340 11:128891445-128891445
7 KCNJ5 NM_000890.5(KCNJ5): c.-284_-283insAAGAGA insertion Uncertain significance rs886048005 11:128761343-128761344 11:128891448-128891449
8 KCNJ5 NM_000890.5(KCNJ5): c.-289_-288GA[20] short repeat Uncertain significance rs71057905 11:128761366-128761371 11:128891471-128891476
9 KCNJ5 NM_000890.5(KCNJ5): c.-289_-288GA[18] short repeat Uncertain significance rs71057905 11:128761370-128761371 11:128891475-128891476
10 KCNJ5 NM_000890.5(KCNJ5): c.-289_-288GA[19] short repeat Uncertain significance rs71057905 11:128761368-128761371 11:128891473-128891476
11 KCNJ5 NM_000890.5(KCNJ5): c.-258_-255del deletion Uncertain significance rs886048008 11:128761369-128761372 11:128891474-128891477
12 KCNJ5 NM_000890.5(KCNJ5): c.*861_*865GTTTT[8] short repeat Uncertain significance rs36205004 11:128787527-128787531 11:128917632-128917636
13 KCNJ5 NM_000890.5(KCNJ5): c.*103G> C single nucleotide variant Uncertain significance rs886048012 11:128786729-128786729 11:128916834-128916834
14 KCNJ5 NM_000890.5(KCNJ5): c.*200C> A single nucleotide variant Uncertain significance rs756204980 11:128786826-128786826 11:128916931-128916931
15 KCNJ5 NM_000890.5(KCNJ5): c.*228G> T single nucleotide variant Uncertain significance rs886048013 11:128786854-128786854 11:128916959-128916959
16 KCNJ5 NM_000890.5(KCNJ5): c.*667C> T single nucleotide variant Uncertain significance rs886048014 11:128787293-128787293 11:128917398-128917398
17 KCNJ5 NM_000890.5(KCNJ5): c.*747A> G single nucleotide variant Uncertain significance rs886048015 11:128787373-128787373 11:128917478-128917478
18 KCNJ5 NM_000890.5(KCNJ5): c.-303_-291delinsGAGAG indel Uncertain significance rs886047988 11:128761324-128761336 11:128891429-128891441
19 KCNJ5 NM_000890.5(KCNJ5) indel Uncertain significance rs886047988 11:128761324-128761336 11:128891429-128891441
20 KCNJ5 NM_000890.5(KCNJ5): c.-301_-291delinsG indel Uncertain significance rs886047990 11:128761326-128761336 11:128891431-128891441
21 KCNJ5 NM_000890.5(KCNJ5): c.-301_-291delinsGAGAGAGAGAGAGAG indel Uncertain significance rs886047990 11:128761326-128761336 11:128891431-128891441
22 KCNJ5 NM_000890.5(KCNJ5): c.-295_-294GA[3] short repeat Uncertain significance rs886047994 11:128761331-128761332 11:128891436-128891437
23 KCNJ5 NM_000890.5(KCNJ5): c.-295_-291delinsGAGAGAGAGAGAG indel Uncertain significance rs886047995 11:128761332-128761336 11:128891437-128891441
24 KCNJ5 NM_000890.5(KCNJ5): c.-295_-291delinsGAGAGAGAGAGAGAGAGAG indel Uncertain significance rs886047995 11:128761332-128761336 11:128891437-128891441
25 KCNJ5 NM_000890.5(KCNJ5): c.-293C> G single nucleotide variant Uncertain significance rs376640553 11:128761334-128761334 11:128891439-128891439
26 KCNJ5 NM_000890.5(KCNJ5): c.-293_-291delinsGAGAGAGAGAGAGAGAG indel Uncertain significance rs886047998 11:128761334-128761336 11:128891439-128891441
27 KCNJ5 NM_000890.5(KCNJ5): c.-303_-291delinsGAG indel Uncertain significance rs886047988 11:128761324-128761336 11:128891429-128891441
28 KCNJ5 NM_000890.5(KCNJ5): c.-295C> G single nucleotide variant Uncertain significance rs372328307 11:128761332-128761332 11:128891437-128891437
29 KCNJ5 NM_000890.5(KCNJ5): c.-295_-291delinsGAGAGAGAGAG indel Uncertain significance rs886047995 11:128761332-128761336 11:128891437-128891441
30 KCNJ5 NM_000890.5(KCNJ5): c.-294_-293insGAGA insertion Uncertain significance rs886047996 11:128761333-128761334 11:128891438-128891439
31 KCNJ5 NM_000890.5(KCNJ5): c.-293_-291delinsGAGAGAGAGAGAGAGAGAG indel Uncertain significance rs886047998 11:128761334-128761336 11:128891439-128891441
32 KCNJ5 NM_000890.5(KCNJ5): c.*1024A> G single nucleotide variant Uncertain significance rs886048018 11:128787650-128787650 11:128917755-128917755
33 KCNJ5 NM_000890.5(KCNJ5): c.*1151C> T single nucleotide variant Uncertain significance rs886048019 11:128787777-128787777 11:128917882-128917882
34 KCNJ5 NM_000890.5(KCNJ5): c.968T> C (p.Met323Thr) single nucleotide variant Uncertain significance rs886048011 11:128786334-128786334 11:128916439-128916439
35 KCNJ5 NM_000890.5(KCNJ5): c.-293_-291delinsGAGAGAGAGAGAG indel Uncertain significance rs886047998 11:128761334-128761336 11:128891439-128891441
36 KCNJ5 NM_000890.5(KCNJ5): c.-297_-291delinsGAGAGAGAGAGAGAGAG indel Uncertain significance rs886047993 11:128761330-128761336 11:128891435-128891441
37 KCNJ5 NM_000890.5(KCNJ5): c.-297_-291delinsGAGAGAGAGAGAGAG indel Uncertain significance rs886047993 11:128761330-128761336 11:128891435-128891441
38 KCNJ5 NM_000890.5(KCNJ5): c.-299_-291delinsGAGAG indel Uncertain significance rs886047992 11:128761328-128761336 11:128891433-128891441
39 KCNJ5 NM_000890.5(KCNJ5): c.-305_-291delinsGAGAG indel Uncertain significance rs886047987 11:128761322-128761336 11:128891427-128891441
40 KCNJ5 NM_000890.5(KCNJ5): c.*1323del deletion Uncertain significance rs886048020 11:128787949-128787949 11:128918054-128918054
41 KCNJ5 NM_000890.5(KCNJ5): c.*978T> G single nucleotide variant Uncertain significance rs886048017 11:128787604-128787604 11:128917709-128917709
42 KCNJ5 NM_000890.5(KCNJ5): c.*936C> G single nucleotide variant Uncertain significance rs77525858 11:128787562-128787562 11:128917667-128917667
43 KCNJ5 NM_000890.5(KCNJ5): c.800G> A (p.Arg267His) single nucleotide variant Uncertain significance rs886048010 11:128781968-128781968 11:128912073-128912073
44 KCNJ5 NM_000890.5(KCNJ5): c.-253G> T single nucleotide variant Uncertain significance rs886048009 11:128761374-128761374 11:128891479-128891479
45 KCNJ5 NM_000890.5(KCNJ5): c.-285G> C single nucleotide variant Uncertain significance rs886048006 11:128761342-128761342 11:128891447-128891447
46 KCNJ5 NM_000890.5(KCNJ5): c.-291delinsGAGAGAGAG indel Uncertain significance rs886048003 11:128761336-128761336 11:128891441-128891441
47 KCNJ5 NM_000890.5(KCNJ5): c.-291_-286del deletion Uncertain significance rs886048002 11:128761336-128761341 11:128891441-128891446
48 KCNJ5 NM_000890.5(KCNJ5): c.-291_-288del deletion Uncertain significance rs886048001 11:128761336-128761339 11:128891441-128891444
49 KCNJ5 NM_000890.5(KCNJ5): c.-272A> G single nucleotide variant Uncertain significance rs886048007 11:128761355-128761355 11:128891460-128891460
50 KCNJ5 NM_000890.5(KCNJ5): c.-289G> C single nucleotide variant Uncertain significance rs60658163 11:128761338-128761338 11:128891443-128891443

Expression for Familial Hyperaldosteronism

Search GEO for disease gene expression data for Familial Hyperaldosteronism.

Pathways for Familial Hyperaldosteronism

Pathways related to Familial Hyperaldosteronism according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.79 KCNJ5 CYP11B2 CYP11B1 CACNA1H AGTR1
2
Show member pathways
10.28 CYP11B2 CYP11B1

GO Terms for Familial Hyperaldosteronism

Biological processes related to Familial Hyperaldosteronism according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 regulation of ion transmembrane transport GO:0034765 9.61 KCNJ5 CLCN2 CACNA1H
2 cellular response to hormone stimulus GO:0032870 9.5 CYP11B2 CYP11B1 CACNA1H
3 sterol metabolic process GO:0016125 9.46 CYP11B2 CYP11B1
4 cellular response to peptide hormone stimulus GO:0071375 9.43 MEN1 CYP11B2 CYP11B1
5 C21-steroid hormone biosynthetic process GO:0006700 9.4 CYP11B2 CYP11B1
6 glucocorticoid biosynthetic process GO:0006704 9.37 CYP11B2 CYP11B1
7 cellular response to potassium ion GO:0035865 9.33 CYP11B2 CYP11B1 CACNA1H
8 cortisol biosynthetic process GO:0034651 9.13 CYP11B2 CYP11B1 CACNA1H
9 aldosterone biosynthetic process GO:0032342 8.8 CYP11B2 CYP11B1 CACNA1H

Molecular functions related to Familial Hyperaldosteronism according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 steroid 11-beta-monooxygenase activity GO:0004507 8.96 CYP11B2 CYP11B1
2 corticosterone 18-monooxygenase activity GO:0047783 8.62 CYP11B2 CYP11B1

Sources for Familial Hyperaldosteronism

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
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50 NCIt
51 NDF-RT
54 NINDS
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57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
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73 UMLS via Orphanet
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