MCID: LDD002
MIFTS: 52

Liddle Syndrome malady

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

Summaries for Liddle Syndrome

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22Genetics Home Reference, 44NIH Rare Diseases, 48OMIM, 34MalaCards
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NIH Rare Diseases:44 Liddle syndromeĀ 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: Liddle Syndrome, also known as pseudoaldosteronism, is related to hypertension and pseudohypoaldosteronism, and has symptoms including asthenia/fatigue/weakness, muscle weakness/flaccidity and transient cerebral ischemia/stroke. 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 kidney and brain, and related mouse phenotypes are respiratory system and cardiovascular system.

Genetics Home Reference:22 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:48 177200

Aliases & Classifications for Liddle Syndrome

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9Disease Ontology, 10diseasecard, 44NIH Rare Diseases, 22Genetics Home Reference, 48OMIM, 11DISEASES, 50Orphanet, 63UMLS, 36MeSH, 27ICD10 via Orphanet, 60SNOMED-CT via Orphanet, 64UMLS via Orphanet, 37MESH via Orphanet
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Classifications:



Characteristics (Orphanet epidemiological data):

50
liddle syndrome:
Inheritance: Autosomal dominant; Prevalence: <1/1000000; Age of onset: Childhood; Age of death: Adult


Aliases & Descriptions:

liddle syndrome 9 10 44 22 48 11 50 63
pseudoaldosteronism 9 44 22 50
pseudoprimary hyperaldosteronism 22
pseudohyperaldosteronism type 1 50
liddle's syndrome 44


External Ids:

Disease Ontology9 DOID:0050477
MeSH36 D056929
OMIM48 177200
ICD10 via Orphanet27 I15.1
SNOMED-CT via Orphanet60 71275003
UMLS via Orphanet64 C0221043
MESH via Orphanet37 D056929

Related Diseases for Liddle Syndrome

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18GeneCards, 19GeneDecks
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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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48OMIM, 50Orphanet
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Symptoms by clinical synopsis from OMIM:

177200

Clinical features from OMIM:

177200

Symptoms:

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

Drugs & Therapeutics for Liddle Syndrome

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6CenterWatch, 43NIH Clinical Center, 7ClinicalTrials
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Approved drugs:

Search CenterWatch for Liddle Syndrome

Drug clinical trials:

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Search CenterWatch for Liddle Syndrome

Genetic Tests for Liddle Syndrome

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Anatomical Context for Liddle Syndrome

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32LifeMap Discoveryā„¢, 34MalaCards
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MalaCards organs/tissues related to Liddle Syndrome:

34
Kidney, Brain

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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38MGI
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MGI Mouse Phenotypes related to Liddle Syndrome:

38
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053888.4IGF1, SCNN1B, SCNN1A, SCNN1G, NEDD4L
2MP:00053858.2WNK4, REN, NEDD4L, SCNN1B, IGF1
3MP:00028738.2IGF1, SCNN1B, SCNN1A, SCNN1G, REN
4MP:00053677.7WNK4, IGF1, SCNN1B, SCNN1A, SCNN1G, NEDD4L
5MP:00053767.6IGF1, SCNN1B, SCNN1A, SCNN1G, NEDD4L, REN
6MP:00107687.4IGF1, SCNN1B, SCNN1A, SCNN1G, SEC24D, NEDD4L

Publications for Liddle Syndrome

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53PubMed
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Articles related to Liddle Syndrome:

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

Variations for Liddle Syndrome

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65UniProtKB/Swiss-Prot, 1 National Center for Biotechnology Information (Clinvar)
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UniProtKB/Swiss-Prot genetic disease variations for Liddle Syndrome:

65
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:

1
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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2BioGPS, 16Gene Expression Omnibus DataSets
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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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51PathCards, 61Thomson Reuters, 54QIAGEN, 31KEGG, 56Reactome, 13EMD Millipore, 39NCBI BioSystems Database, 52PharmGKB
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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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46Novoseek, 25HMDB, 12DrugBank, 30IUPHAR, 52PharmGKB
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Compounds related to Liddle Syndrome according to GeneCards/GeneDecks:

idCompoundScoreTop Affiliating Genes
1triamterene46 25 1211.7SCNN1B, SCNN1A, SCNN1G
2hydrochlorothiazide46 30 52 25 1213.6REN, NEDD4L
3thiazide469.5SCNN1A, REN, WNK4
4clonidine46 52 30 1212.5IGF1, REN
5mannose 6-phosphate46 2510.5REN, IGF1
6nacl469.5WNK4, REN, SCNN1A
7losartan46 52 30 1212.4REN, IGF1
8amiloride46 30 1211.3REN, SCNN1G, SCNN1A, SCNN1B
9androstenedione46 2510.2REN, IGF1
10sodium46 259.4WNK4, REN, NEDD4L, SCNN1G, SCNN1A, SCNN1B

GO Terms for genes affiliated with Liddle Syndrome

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17Gene Ontology
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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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4CDC
14ExPASy
15FMA
23GTR
24HGMD
25HMDB
26ICD10
27ICD10 via Orphanet
28ICD9CM
30IUPHAR
31KEGG
36MeSH
37MESH via Orphanet
38MGI
41NCIt
42NDF-RT
45NINDS
46Novoseek
48OMIM
49OMIM via Orphanet
53PubMed
54QIAGEN
60SNOMED-CT via Orphanet
63UMLS
64UMLS via Orphanet