MCID: LDD002
MIFTS: 52

Liddle Syndrome malady

Genetic diseases, Rare diseases, Cardiovascular diseases, Nephrological diseases categories

Summaries for Liddle Syndrome

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NIH Rare Diseases:41 Liddle syndrome is a rare, inherited form of high blood pressure (hypertension). the condition is characterized by severe, early-onset hypertension associated with decreased levels of potassium, renin and aldosterone in blood plasma. children usually have no symptoms; adults can present with symptoms of low potassium levels (hypokalemia) such as weakness, fatigue, muscle pain (myalgia), constipation or palpitations. it is caused by mutations in either the scnn1b or scnn1g genes and is inherited in an autosomal dominant manner. treatment may include a low sodium diet and potassium-sparing diuretics to reduce blood pressure and normalize potassium levels. conventional anti-hypertensive therapies are not effective. last updated: 9/21/2012

MalaCards based summary: Liddle Syndrome, also known as pseudoaldosteronism, is related to pseudohypoaldosteronism and hyperaldosteronism, and has symptoms including hypertension, constipation and hypokalemia. An important gene associated with Liddle Syndrome is SCNN1B (sodium channel, non-voltage-gated 1, beta subunit), and among its related pathways are CFTR dependent regulation of ion channels in Airway Epithelium norm and CF and G-Beta Gamma Signaling. The compounds triamterene and hydrochlorothiazide have been mentioned in the context of this disorder. Affiliated tissues include heart, brain and kidney, and related mouse phenotypes are respiratory system and cardiovascular system.

Genetics Home Reference:21 Liddle syndrome is an inherited form of high blood pressure (hypertension). This condition is characterized by severe hypertension that begins unusually early in life, often in childhood, although some affected individuals are not diagnosed until adulthood. Some people with Liddle syndrome have no additional signs or symptoms, especially in childhood. Over time, however, untreated hypertension can lead to heart disease or stroke, which may be fatal.

Description from OMIM:45 177200

Aliases & Classifications for Liddle Syndrome

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Sources:
45OMIM, 30LifeMap Discovery®, 9Disease Ontology, 10diseasecard, 41NIH Rare Diseases, 21Genetics Home Reference, 11DISEASES, 47Orphanet, 60UMLS, 22GTR, 43Novoseek, 33MeSH, 34MESH via Orphanet, 26ICD10 via Orphanet, 61UMLS via Orphanet
See all sources

Liddle Syndrome, Aliases & Descriptions:

Name: Liddle Syndrome 45 30 9 10 41 21 11 47 60
Pseudoaldosteronism 9 41 21 47
Pseudoprimary Hyperaldosteronism 21 22
 
Pseudohyperaldosteronism Type 1 41 47
Liddle's Syndrome 41
Liddles Syndrome 43


Classifications:



Characteristics (Orphanet epidemiological data):

47
liddle syndrome:
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Age of death: adult


External Ids:

OMIM45 177200
Disease Ontology9 DOID:0050477
MeSH33 D056929
Orphanet47 526
MESH via Orphanet34 D056929
ICD10 via Orphanet26 I15.1
UMLS via Orphanet61 C0221043

Related Diseases for Liddle Syndrome

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Graphical network of diseases related to Liddle Syndrome:



Diseases related to liddle syndrome

Symptoms for Liddle Syndrome

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Symptoms by clinical synopsis from OMIM:

177200

Clinical features from OMIM:

177200

Symptoms:

 47 (show all 10)
  • constipation
  • cardiac rhythm disorder/arrhythmia
  • chronic arterial hypertension
  • hypokalemia
  • autosomal dominant inheritance
  • renal disease/nephropathy
  • renal failure
  • transient cerebral ischemia/stroke
  • muscle weakness/flaccidity
  • asthenia/fatigue/weakness

HPO human phenotypes related to Liddle Syndrome:

(show all 15)
id Description Frequency HPO Source Accession
1 hypertension hallmark (90%) HP:0000822
2 constipation hallmark (90%) HP:0002019
3 hypokalemia hallmark (90%) HP:0002900
4 arrhythmia hallmark (90%) HP:0011675
5 renal insufficiency typical (50%) HP:0000083
6 nephropathy typical (50%) HP:0000112
7 muscle weakness typical (50%) HP:0001324
8 cerebral ischemia typical (50%) HP:0002637
9 autosomal dominant inheritance HP:0000006
10 renal insufficiency HP:0000083
11 hypertension HP:0000822
12 hypokalemic alkalosis HP:0001949
13 hypokalemia HP:0002900
14 decreased circulating renin level HP:0003351
15 hypoaldosteronism HP:0004319

Drugs & Therapeutics for Liddle Syndrome

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Drug clinical trials:

Search ClinicalTrials for Liddle Syndrome

Search NIH Clinical Center for Liddle Syndrome

Genetic Tests for Liddle Syndrome

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Genetic tests related to Liddle Syndrome:

id Genetic test Affiliating Genes
1 Pseudoprimary Hyperaldosteronism22

Anatomical Context for Liddle Syndrome

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MalaCards organs/tissues related to Liddle Syndrome:

31
Heart, Brain, Kidney

LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database

Cells/anatomical compartments in embryo or adult related to Liddle Syndrome:
id TissueAnatomical CompartmentCell Relevance
1 KidneyRenal Collecting Duct SystemCollecting Duct Cells Potential therapeutic candidate, affected by disease

Animal Models for Liddle Syndrome or affiliated genes

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MGI Mouse Phenotypes related to Liddle Syndrome:

35
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053888.4IGF1, SCNN1B, SCNN1A, SCNN1G, NEDD4L
2MP:00053858.2REN, NEDD4L, SCNN1B, IGF1, WNK4
3MP:00028738.2SCNN1G, REN, IGF1, SCNN1B, SCNN1A
4MP:00053677.7IGF1, WNK4, REN, NEDD4L, SCNN1G, SCNN1A
5MP:00053767.6IGF1, SCNN1B, SCNN1A, SCNN1G, NEDD4L, REN
6MP:00107687.4SCNN1B, SCNN1A, SCNN1G, SEC24D, NEDD4L, IGF1

Publications for Liddle Syndrome

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Articles related to Liddle Syndrome:

(show all 34)
idTitleAuthorsYear
1
Liddle syndrome phenotype in an octogenarian. (25427961)
2015
2
A Case of Liddle Syndrome: Author's Reply. (24827082)
2014
3
A case of liddle syndrome: correspondence. (24827081)
2014
4
Phenotype-genotype analysis in two Chinese families with Liddle syndrome. (24474657)
2014
5
A novel frameshift mutation of epithelial sodium channel I^-subunit leads to Liddle syndrome in an isolated case. (25378078)
2014
6
A case of Liddle Syndrome. (23307437)
2013
7
A family with Liddle syndrome caused by a novel missense mutation in the PY motif of the beta-subunit of the epithelial sodium channel. (22809657)
2013
8
Liddle syndrome in a Serbian family and literature review of underlying mutations. (21956615)
2012
9
Salt-induced hypertension in a mouse model of Liddle syndrome is mediated by epithelial sodium channels in the brain. (22802227)
2012
10
High prevalence of liddle syndrome phenotype among hypertensive US Veterans in Northwest Louisiana. (21054772)
2010
11
Role of the UPS in Liddle syndrome. (19007435)
2008
12
The PY motif of ENaC, mutated in Liddle syndrome, regulates channel internalization, sorting and mobilization from subapical pool. (17605762)
2007
13
A novel epithelial sodium channel gamma-subunit de novo frameshift mutation leads to Liddle syndrome. (17634077)
2007
14
Liddle syndrome caused by P616R mutation of the epithelial sodium channel beta subunit. (15856328)
2005
15
A novel epithelial sodium channel beta-subunit mutation associated with hypertensive Liddle syndrome. (15690192)
2005
16
Distinction between Liddle syndrome and apparent mineralocorticoid excess. (14625721)
2004
17
Dysfunction of the epithelial sodium channel expressed in the kidney of a mouse model for Liddle syndrome. (12937297)
2003
18
The distinction between Liddle syndrome and apparent mineralocorticoid excess. (12759812)
2003
19
Liddle syndrome in a newborn infant. (12185466)
2002
20
A frameshift mutation of beta subunit of epithelial sodium channel in a case of isolated Liddle syndrome. (12473861)
2002
21
Liddle syndrome: genetics and mechanisms of Na+ channel defects. (11780687)
2001
22
Diagnosis of Liddle syndrome by genetic analysis of beta and gamma subunits of epithelial sodium channel--a report of five affected family members. (11393671)
2001
23
Quantitative trait loci for blood pressure exist near the IGF-1, the Liddle syndrome, the angiotensin II-receptor gene and the renin loci in man. (10446938)
1999
24
The diagnosis of Liddle syndrome by identification of a mutation in the beta subunit of the epithelial sodium channel. (9643296)
1998
25
Mutations causing Liddle syndrome reduce sodium-dependent downregulation of the epithelial sodium channel in the Xenopus oocyte expression system. (9637708)
1998
26
Liddle syndrome: an autosomal dominant form of human hypertension. (9452995)
1998
27
The ENaC channel as the primary determinant of two human diseases: Liddle syndrome and pseudohypoaldosteronism. (8987044)
1996
28
Identification of a PY motif in the epithelial Na channel subunits as a target sequence for mutations causing channel activation found in Liddle syndrome. (8665845)
1996
29
Cell surface expression of the epithelial Na channel and a mutant causing Liddle syndrome: a quantitative approach. (8986818)
1996
30
A de novo missense mutation of the beta subunit of the epithelial sodium channel causes hypertension and Liddle syndrome, identifying a proline-rich segment critical for regulation of channel activity. (8524790)
1995
31
Hypertension caused by a truncated epithelial sodium channel gamma subunit: genetic heterogeneity of Liddle syndrome. (7550319)
1995
32
Liddle syndrome: clinical and cellular abnormalities. (8027210)
1994
33
Liddle syndrome: sodium influx into RBC. (7365623)
1980
34
Liddle syndrome. (480019)
1979

Variations for Liddle Syndrome

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UniProtKB/Swiss-Prot genetic disease variations for Liddle Syndrome:

62
id Symbol AA change Variation ID SNP ID
1SCNN1Bp.Pro616LeuVAR_007128
2SCNN1Bp.Pro616SerVAR_007129
3SCNN1Bp.Pro617SerVAR_026520
4SCNN1Bp.Pro618ArgVAR_026521
5SCNN1Bp.Tyr620HisVAR_026522

Clinvar genetic disease variations for Liddle Syndrome:

6
id Gene Variation Type Significance SNP ID Assembly Location
1SCNN1GNM_001039.3(SCNN1G): c.1718G> A (p.Trp573Ter)single nucleotide variantPathogenicrs137853342GRCh37Chr 16, 23226558: 23226558
2SCNN1BNM_000336.2(SCNN1B): c.1696C> T (p.Arg566Ter)single nucleotide variantPathogenicrs137852704GRCh37Chr 16, 23391895: 23391895
3SCNN1BNM_000336.2(SCNN1B): c.1847C> T (p.Pro616Leu)single nucleotide variantPathogenicrs387906402GRCh37Chr 16, 23392046: 23392046
4SCNN1BNM_000336.2(SCNN1B): c.1858T> C (p.Tyr620His)single nucleotide variantPathogenicrs137852707GRCh37Chr 16, 23392057: 23392057
5SCNN1BSCNN1B, 1-BP INS, 592CinsertionPathogenic
6SCNN1BSCNN1B, 32-BP DELdeletionPathogenic
7SCNN1BNM_000336.2(SCNN1B): c.1849C> T (p.Pro617Ser)single nucleotide variantPathogenicrs137852708GRCh37Chr 16, 23392048: 23392048
8SCNN1BNM_000336.2(SCNN1B): c.1847C> G (p.Pro616Arg)single nucleotide variantPathogenicrs387906402GRCh37Chr 16, 23392046: 23392046

Expression for genes affiliated with Liddle Syndrome

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Search GEO for disease gene expression data for Liddle Syndrome.

Pathways for genes affiliated with Liddle Syndrome

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Pathways related to Liddle Syndrome according to GeneCards Suite gene sharing:

(show all 12)
idSuper pathways (with members indented)ScoreTop Affiliating Genes
19.5SCNN1B, SCNN1A, SCNN1G
2
Show member pathways
9.5SCNN1B, SCNN1A, SCNN1G
3
Show member pathways
9.5SCNN1B, SCNN1A, SCNN1G
4
Show member pathways
9.5SCNN1G, SCNN1A, SCNN1B
59.5SCNN1G, SCNN1A, SCNN1B
6
Show member pathways
9.5REN, IGF1
7
Show member pathways
8.9IGF1, SCNN1B, SCNN1A, SCNN1G
8
Show member pathways
8.6SCNN1B, SCNN1A, SCNN1G, NEDD4L, WNK4
98.6WNK4, NEDD4L, SCNN1G, SCNN1A, SCNN1B
10
Show member pathways
8.6SCNN1B, SCNN1A, SCNN1G, NEDD4L, WNK4
118.4IGF1, SCNN1B, SCNN1A, SCNN1G, NEDD4L

Compounds for genes affiliated with Liddle Syndrome

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Sources:
43Novoseek, 24HMDB, 12DrugBank, 28IUPHAR, 49PharmGKB
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Compounds related to Liddle Syndrome according to GeneCards Suite gene sharing:

idCompoundScoreTop Affiliating Genes
1triamterene43 24 1211.7SCNN1B, SCNN1A, SCNN1G
2hydrochlorothiazide43 28 49 24 1213.6REN, NEDD4L
3thiazide439.5SCNN1A, REN, WNK4
4clonidine43 49 28 1212.5IGF1, REN
5mannose 6-phosphate43 2410.5REN, IGF1
6nacl439.5WNK4, REN, SCNN1A
7losartan43 49 28 1212.4REN, IGF1
8amiloride43 28 1211.3REN, SCNN1G, SCNN1A, SCNN1B
9androstenedione43 2410.2REN, IGF1
10sodium43 249.4WNK4, REN, NEDD4L, SCNN1G, SCNN1A, SCNN1B

GO Terms for genes affiliated with Liddle Syndrome

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Cellular components related to Liddle Syndrome according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1sodium channel complexGO:00347069.6SCNN1G, SCNN1A, SCNN1B
2external side of plasma membraneGO:00098979.5SCNN1G, SCNN1A, SCNN1B
3apical plasma membraneGO:00163249.4SCNN1B, SCNN1A, SCNN1G
4cytosolGO:00058297.8KLHL3, NEDD4L, HERC5, SEC24D, SCNN1A
5plasma membraneGO:00058867.7IGF1, SCNN1B, SCNN1A, SCNN1G, NEDD4L, REN

Biological processes related to Liddle Syndrome according to GeneCards Suite gene sharing:

(show all 16)
idNameGO IDScoreTop Affiliating Genes
1distal tubule morphogenesisGO:00721569.8KLHL3, WNK4
2multicellular organismal water homeostasisGO:00508919.8SCNN1B, SCNN1A, SCNN1G
3sodium ion homeostasisGO:00550789.8SCNN1B, SCNN1G, SCNN1A
4sensory perception of tasteGO:00509099.8SCNN1A, SCNN1G, SCNN1B
5response to stimulusGO:00508969.7SCNN1A, SCNN1G, SCNN1B
6renal sodium ion absorptionGO:00702949.7WNK4, KLHL3
7sodium ion transmembrane transportGO:00357259.7SCNN1B, SCNN1G, SCNN1A
8ion homeostasisGO:00508019.6KLHL3, WNK4
9water homeostasisGO:00301049.4IGF1, NEDD4L
10excretionGO:00075889.3SCNN1G, NEDD4L, SCNN1B, SCNN1A
11sodium ion transportGO:00068149.3NEDD4L, SCNN1B, SCNN1A, SCNN1G
12ion transmembrane transportGO:00342209.2SCNN1B, SCNN1A, SCNN1G, NEDD4L
13protein K48-linked ubiquitinationGO:00709369.2NEDD4L, KLHL3
14cellular protein metabolic processGO:00442679.0SEC24D, REN, IGF1
15transmembrane transportGO:00550858.9NEDD4L, SCNN1G, SCNN1A, SCNN1B
16protein ubiquitination involved in ubiquitin-dependent protein catabolic processGO:00427878.9KLHL3, NEDD4L, HERC5

Molecular functions related to Liddle Syndrome according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1ligand-gated sodium channel activityGO:00152809.5SCNN1G, SCNN1A, SCNN1B
2insulin-like growth factor receptor bindingGO:00051599.5REN, IGF1
3WW domain bindingGO:00506999.4SCNN1B, SCNN1A, SCNN1G
4protein bindingGO:00055156.4IGF1, SCNN1B, SCNN1A, SCNN1G, HERC5, NEDD4L

Products for genes affiliated with Liddle Syndrome

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Sources for Liddle Syndrome

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
33MeSH
34MESH via Orphanet
35MGI
38NCIt
39NDF-RT
42NINDS
43Novoseek
45OMIM
46OMIM via Orphanet
50PubMed
51QIAGEN
56SNOMED-CT via Orphanet
60UMLS
61UMLS via Orphanet