MCID: LDD002
MIFTS: 54

Liddle Syndrome malady

Genetic diseases, Rare diseases, Cardiovascular diseases, Nephrological diseases categories
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Summaries for Liddle Syndrome

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NIH Rare Diseases:42 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 hypertension and pseudohypoaldosteronism, and has symptoms including constipation, cardiac rhythm disorder/arrhythmia and chronic arterial hypertension. 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:46 177200

Aliases & Classifications for Liddle Syndrome

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Sources:
30LifeMap Discovery®, 8Disease Ontology, 9diseasecard, 42NIH Rare Diseases, 21Genetics Home Reference, 46OMIM, 10DISEASES, 48Orphanet, 62UMLS, 44Novoseek, 34MeSH, 35MESH via Orphanet, 26ICD10 via Orphanet, 63UMLS via Orphanet
See all sources

Liddle Syndrome, Aliases & Descriptions:

Name: Liddle Syndrome 30 8 9 42 21 46 10 48 62
Pseudoaldosteronism 8 42 21 48 62
Pseudoprimary Hyperaldosteronism 21 62
 
Pseudohyperaldosteronism Type 1 48
Liddle's Syndrome 42
Liddles Syndrome 44


Classifications:



Characteristics (Orphanet epidemiological data):

48
liddle syndrome:
Inheritance: Autosomal dominant; Prevalence: <1/1000000; Age of onset: Childhood; Age of death: Adult


External Ids:

Disease Ontology8 DOID:0050477
OMIM46 177200
MeSH34 D056929
MESH via Orphanet35 D056929
ICD10 via Orphanet26 I15.1
UMLS via Orphanet63 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:

48 (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:

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Search NIH Clinical Center for Liddle Syndrome

Genetic Tests for Liddle Syndrome

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Anatomical Context for Liddle Syndrome

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MalaCards organs/tissues related to Liddle Syndrome:

32
Heart, Brain, Kidney

LifeMap Discovery
The database of embryonic development, stem cell research and regenerative medicine

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:

36
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 33)
idTitleAuthorsYear
1
A Case of Liddle Syndrome: Author's Reply. (24827082)
2014
2
A case of liddle syndrome: correspondence. (24827081)
2014
3
Phenotype-genotype analysis in two Chinese families with Liddle syndrome. (24474657)
2014
4
A novel frameshift mutation of epithelial sodium channel I^-subunit leads to Liddle syndrome in an isolated case. (25378078)
2014
5
A case of Liddle Syndrome. (23307437)
2013
6
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
7
Liddle syndrome in a Serbian family and literature review of underlying mutations. (21956615)
2012
8
Salt-induced hypertension in a mouse model of Liddle syndrome is mediated by epithelial sodium channels in the brain. (22802227)
2012
9
High prevalence of liddle syndrome phenotype among hypertensive US Veterans in Northwest Louisiana. (21054772)
2010
10
Role of the UPS in Liddle syndrome. (19007435)
2008
11
The PY motif of ENaC, mutated in Liddle syndrome, regulates channel internalization, sorting and mobilization from subapical pool. (17605762)
2007
12
A novel epithelial sodium channel gamma-subunit de novo frameshift mutation leads to Liddle syndrome. (17634077)
2007
13
Liddle syndrome caused by P616R mutation of the epithelial sodium channel beta subunit. (15856328)
2005
14
A novel epithelial sodium channel beta-subunit mutation associated with hypertensive Liddle syndrome. (15690192)
2005
15
Distinction between Liddle syndrome and apparent mineralocorticoid excess. (14625721)
2004
16
Dysfunction of the epithelial sodium channel expressed in the kidney of a mouse model for Liddle syndrome. (12937297)
2003
17
The distinction between Liddle syndrome and apparent mineralocorticoid excess. (12759812)
2003
18
Liddle syndrome in a newborn infant. (12185466)
2002
19
A frameshift mutation of beta subunit of epithelial sodium channel in a case of isolated Liddle syndrome. (12473861)
2002
20
Liddle syndrome: genetics and mechanisms of Na+ channel defects. (11780687)
2001
21
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
22
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
23
The diagnosis of Liddle syndrome by identification of a mutation in the beta subunit of the epithelial sodium channel. (9643296)
1998
24
Mutations causing Liddle syndrome reduce sodium-dependent downregulation of the epithelial sodium channel in the Xenopus oocyte expression system. (9637708)
1998
25
Liddle syndrome: an autosomal dominant form of human hypertension. (9452995)
1998
26
The ENaC channel as the primary determinant of two human diseases: Liddle syndrome and pseudohypoaldosteronism. (8987044)
1996
27
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
28
Cell surface expression of the epithelial Na channel and a mutant causing Liddle syndrome: a quantitative approach. (8986818)
1996
29
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
30
Hypertension caused by a truncated epithelial sodium channel gamma subunit: genetic heterogeneity of Liddle syndrome. (7550319)
1995
31
Liddle syndrome: clinical and cellular abnormalities. (8027210)
1994
32
Liddle syndrome: sodium influx into RBC. (7365623)
1980
33
Liddle syndrome. (480019)
1979

Variations for Liddle Syndrome

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

64
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 Name 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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Expression patterns in normal tissues for genes affiliated with Liddle Syndrome

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/GeneDecks:

(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
5
Show member pathways
9.5SCNN1G, SCNN1A, SCNN1B
69.5SCNN1G, SCNN1A, SCNN1B
7
Show member pathways
9.5REN, IGF1
8
Show member pathways
8.9IGF1, SCNN1B, SCNN1A, SCNN1G
9
Show member pathways
8.6SCNN1B, SCNN1A, SCNN1G, NEDD4L, WNK4
108.6WNK4, NEDD4L, SCNN1G, SCNN1A, SCNN1B
11
Show member pathways
8.6SCNN1B, SCNN1A, SCNN1G, NEDD4L, WNK4
128.4IGF1, SCNN1B, SCNN1A, SCNN1G, NEDD4L

Compounds for genes affiliated with Liddle Syndrome

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Sources:
44Novoseek, 24HMDB, 11DrugBank, 28IUPHAR, 50PharmGKB
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Compounds related to Liddle Syndrome according to GeneCards/GeneDecks:

idCompoundScoreTop Affiliating Genes
1triamterene44 24 1111.7SCNN1A, SCNN1G, SCNN1B
2hydrochlorothiazide44 28 50 24 1113.6NEDD4L, REN
3thiazide449.5WNK4, REN, SCNN1A
4clonidine44 50 28 1112.5IGF1, REN
5mannose 6-phosphate44 2410.5IGF1, REN
6nacl449.5WNK4, SCNN1A, REN
7losartan44 50 28 1112.4IGF1, REN
8amiloride44 28 1111.3SCNN1B, SCNN1A, SCNN1G, REN
9androstenedione44 2410.2IGF1, REN
10sodium44 249.4SCNN1B, SCNN1A, SCNN1G, NEDD4L, REN, WNK4

GO Terms for genes affiliated with Liddle Syndrome

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Cellular components related to Liddle Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1sodium channel complexGO:0347069.6SCNN1G, SCNN1A, SCNN1B
2external side of plasma membraneGO:0098979.5SCNN1G, SCNN1A, SCNN1B
3apical plasma membraneGO:0163249.4SCNN1B, SCNN1A, SCNN1G
4cytosolGO:0058297.8KLHL3, NEDD4L, HERC5, SEC24D, SCNN1A
5plasma membraneGO:0058867.7IGF1, SCNN1B, SCNN1A, SCNN1G, NEDD4L, REN

Biological processes related to Liddle Syndrome according to GeneCards/GeneDecks:

(show all 16)
idNameGO IDScoreTop Affiliating Genes
1distal tubule morphogenesisGO:0721569.8KLHL3, WNK4
2multicellular organismal water homeostasisGO:0508919.8SCNN1B, SCNN1A, SCNN1G
3sodium ion homeostasisGO:0550789.8SCNN1B, SCNN1A, SCNN1G
4sensory perception of tasteGO:0509099.8SCNN1G, SCNN1A, SCNN1B
5renal sodium ion absorptionGO:0702949.7WNK4, KLHL3
6response to stimulusGO:0508969.7SCNN1B, SCNN1A, SCNN1G
7ion homeostasisGO:0508019.7WNK4, KLHL3
8sodium ion transmembrane transportGO:0357259.7SCNN1B, SCNN1A, SCNN1G
9water homeostasisGO:0301049.3IGF1, NEDD4L
10excretionGO:0075889.3NEDD4L, SCNN1G, SCNN1A, SCNN1B
11sodium ion transportGO:0068149.3NEDD4L, SCNN1G, SCNN1A, SCNN1B
12ion transmembrane transportGO:0342209.2SCNN1B, SCNN1A, SCNN1G, NEDD4L
13protein K48-linked ubiquitinationGO:0709369.2KLHL3, NEDD4L
14cellular protein metabolic processGO:0442679.0REN, SEC24D, IGF1
15transmembrane transportGO:0550858.9SCNN1B, SCNN1A, SCNN1G, NEDD4L
16protein ubiquitination involved in ubiquitin-dependent protein catabolic processGO:0427878.9KLHL3, NEDD4L, HERC5

Molecular functions related to Liddle Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1ligand-gated sodium channel activityGO:0152809.5SCNN1G, SCNN1A, SCNN1B
2insulin-like growth factor receptor bindingGO:0051599.5REN, IGF1
3WW domain bindingGO:0506999.4SCNN1B, SCNN1A, SCNN1G
4protein bindingGO:0055156.4IGF1, 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
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet