MCID: LDD002
MIFTS: 54

Liddle Syndrome malady

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

Aliases & Classifications for Liddle Syndrome

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Sources:
50OMIM, 33LifeMap Discovery®, 11Disease Ontology, 46NIH Rare Diseases, 24Genetics Home Reference, 13DISEASES, 52Orphanet, 68UniProtKB/Swiss-Prot, 12diseasecard, 37MeSH, 66UMLS, 25GTR, 48Novoseek, 43NCIt, 29ICD10 via Orphanet, 38MESH via Orphanet, 67UMLS via Orphanet, 35MedGen, 60SNOMED-CT, 62The Human Phenotype Ontology
See all MalaCards sources

Aliases & Descriptions for Liddle Syndrome:

Name: Liddle Syndrome 50 33 11 46 24 13 52 68 12 37 66
Pseudoaldosteronism 11 46 24 52 68
Pseudoprimary Hyperaldosteronism 24 25 66
Liddle's Syndrome 11 46
 
Pseudohyperaldosteronism Type 1 52
Liddles Syndrome 48
Lidls 68

Characteristics:

Orphanet epidemiological data:

52
liddle syndrome:
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Age of death: adult

HPO:

62
liddle syndrome:
Inheritance: autosomal dominant inheritance


Classifications:



External Ids:

OMIM50 177200
Disease Ontology11 DOID:0050477
MeSH37 D056929
NCIt43 C84827
Orphanet52 ORPHA526
ICD10 via Orphanet29 I15.1
MESH via Orphanet38 D056929
UMLS via Orphanet67 C0221043
MedGen35 C0221043

Summaries for Liddle Syndrome

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NIH Rare Diseases:46 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 liddle syndrome, scnn1b-related and liddle syndrome, scnn1g-related, and has symptoms including hypertension, constipation and hypokalemia. An important gene associated with Liddle Syndrome is SCNN1B (Sodium Channel Epithelial 1 Beta Subunit), and among its related pathways are Taste transduction and NO-dependent CFTR activation (normal and CF). Affiliated tissues include heart, kidney and brain, and related mouse phenotypes are digestive/alimentary and normal.

Genetics Home Reference:24 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.

OMIM:50 Liddle syndrome is an autosomal dominant disorder characterized by early-onset salt-sensitive hypertension,... (177200) more...

UniProtKB/Swiss-Prot:68 Liddle syndrome: An autosomal dominant disorder characterized by hypertension, hypokalemic alkalosis, and suppression of plasma renin activity and aldosterone secretion.

Related Diseases for Liddle Syndrome

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Diseases in the Liddle Syndrome family:

Liddle Syndrome, Scnn1b-Related Liddle Syndrome, Scnn1g-Related

Diseases related to Liddle Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 33)
idRelated DiseaseScoreTop Affiliating Genes
1liddle syndrome, scnn1b-related12.0
2liddle syndrome, scnn1g-related12.0
3hyperuricemic nephropathy, familial juvenile 110.4CFTR, SCNN1B
4mucinous tubular and spindle renal cell carcinoma10.3REN, SCNN1B, SCNN1G
5microcephaly 4, primary, autosomal recessive10.2CFTR, PARK2
6dystonia 2510.2NR3C2, REN
7benign shuddering attacks10.0HSD11B2, REN
8apparent mineralocorticoid excess10.0
9aseptic osteitis10.0CFTR, SCNN1A, SCNN1B, SCNN1G
10choanal atresia9.9CFTR, SCNN1A, SCNN1B, SCNN1G
11hypodermyasis9.9CYP11B2, REN
12paget disease of bone 49.9NR3C1, NR3C2
13pseudohypoaldosteronism9.9
14pulmonary fibrosis9.8NR3C2, SCNN1A, SCNN1B, SCNN1G
15priapism9.7HSD11B2, NR3C1
16antiphospholipid syndrome9.7HSD11B2, NR3C2, REN
17central nervous system angiosarcoma9.6HSD11B2, REN
18neurilemmoma of the pleura9.6CYP11B2, REN
19benign hypertensive renal disease9.6CYP11B2, NR3C2
20spinal canal and spinal cord meningioma9.6CFTR, CYP11B2, REN
21congenital bilateral absence of vas deferens9.5CFTR, SCNN1A, SCNN1B, SCNN1G, SGK1
22bronchiectasis with or without elevated sweat chloride 29.5NR3C2, SCNN1A, SCNN1B, SCNN1G, SGK1
23cardiovascular organ benign neoplasm9.5CYP11B2, NR3C2, REN
24collecting duct carcinoma9.4CYP11B2, NR3C2, REN
25glioma susceptibility 19.4CYP11B2, HSD11B2
26cataract 21, multiple types9.2HSD11B2, NR3C1, NR3C2, REN
27drug-induced mental disorder8.9CYP11B2, HSD11B2, NR3C2, REN
28hypoaldosteronism, congenital, due to cmo ii deficiency8.4CYP11B2, HSD11B2, NR3C1, NR3C2, REN
29acute myocarditis8.4CYP11B2, HSD11B2, NR3C1, NR3C2, REN
30loeffler endocarditis8.4CYP11B2, HSD11B2, NR3C1, NR3C2, REN
31nasopharyngeal disease8.4CYP11B2, HSD11B2, NR3C1, NR3C2, REN
32hypertension, essential8.1CYP11B2, HSD11B2, NEDD4L, NR3C1, NR3C2, REN
33bronchiectasis with or without elevated sweat chloride 35.9CFTR, CYP11B2, HSD11B2, NEDD4, NEDD4L, NR3C1

Graphical network of the top 20 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:

 52 (show all 9)
  • renal insufficiency
  • nephropathy
  • hypertension
  • muscle weakness
  • constipation
  • cerebral ischemia
  • hypokalemia
  • arrhythmia
  • fatigue

HPO human phenotypes related to Liddle Syndrome:

(show all 14)
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 renal insufficiency HP:0000083
10 hypertension HP:0000822
11 hypokalemic alkalosis HP:0001949
12 hypokalemia HP:0002900
13 decreased circulating renin level HP:0003351
14 hypoaldosteronism HP:0004319

UMLS symptoms related to Liddle Syndrome:


cushingoid facies

Drugs & Therapeutics for Liddle Syndrome

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Interventional clinical trials:

idNameStatusNCT IDPhase
1Juvenile Detention to Community LifeCompletedNCT01910324
2The Chinese Mutation Hotspot of ENaC Causing Liddle's Syndrome and the Association of ENaC Variations and HypertensionSuspendedNCT00448162

Search NIH Clinical Center for Liddle Syndrome


Cochrane evidence based reviews: liddle syndrome

Genetic Tests for Liddle Syndrome

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Genetic tests related to Liddle Syndrome:

id Genetic test Affiliating Genes
1 Pseudoprimary Hyperaldosteronism25

Anatomical Context for Liddle Syndrome

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MalaCards organs/tissues related to Liddle Syndrome:

34
Heart, Kidney, Brain

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:

39 (show all 13)
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053818.4CFTR, HSD11B2, NEDD4L, NR3C1, SCNN1A, SCNN1B
2MP:00028738.2CFTR, HSD11B2, NR3C1, REN, SCNN1A, SCNN1B
3MP:00053698.1HSD11B2, NEDD4L, NR3C1, NR3C2, PARK2, REN
4MP:00053888.1CFTR, NEDD4L, NR3C1, PARK2, SCNN1A, SCNN1B
5MP:00030127.8CFTR, HSD11B2, NEDD4L, NR3C1, PARK2, SGK1
6MP:00053857.1CYP11B2, HSD11B2, NEDD4L, NR3C1, NR3C2, PARK2
7MP:00053866.8CFTR, HSD11B2, NEDD4L, NR3C1, NR3C2, PARK2
8MP:00107686.7CFTR, HSD11B2, NEDD4L, NR3C1, NR3C2, PARK2
9MP:00053676.7CYP11B2, HSD11B2, NEDD4L, NR3C1, NR3C2, REN
10MP:00053786.2CFTR, CYP11B2, NR3C1, NR3C2, PARK2, REN
11MP:00053765.4CFTR, CYP11B2, HSD11B2, NEDD4L, NR3C1, NR3C2

Publications for Liddle Syndrome

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Articles related to Liddle Syndrome:

(show all 37)
idTitleAuthorsYear
1
In Liddle Syndrome, Epithelial Sodium Channel Is Hyperactive Mainly in the Early Part of the Aldosterone-Sensitive Distal Nephron. (27170740)
2016
2
Liddle syndrome in a Turkish family with heterogeneous phenotypes. (27325428)
2016
3
Prevalence of Liddle Syndrome Among Young Hypertension Patients of Undetermined Cause in a Chinese Population. (26075967)
2015
4
Liddle syndrome phenotype in an octogenarian. (25427961)
2015
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: Author's Reply. (24827082)
2014
7
A case of liddle syndrome: correspondence. (24827081)
2014
8
Phenotype-genotype analysis in two Chinese families with Liddle syndrome. (24474657)
2014
9
A case of Liddle Syndrome. (23307437)
2013
10
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
11
Salt-induced hypertension in a mouse model of Liddle syndrome is mediated by epithelial sodium channels in the brain. (22802227)
2012
12
Liddle syndrome in a Serbian family and literature review of underlying mutations. (21956615)
2012
13
High prevalence of liddle syndrome phenotype among hypertensive US Veterans in Northwest Louisiana. (21054772)
2010
14
Role of the UPS in Liddle syndrome. (19007435)
2008
15
The PY motif of ENaC, mutated in Liddle syndrome, regulates channel internalization, sorting and mobilization from subapical pool. (17605762)
2007
16
A novel epithelial sodium channel gamma-subunit de novo frameshift mutation leads to Liddle syndrome. (17634077)
2007
17
Liddle syndrome caused by P616R mutation of the epithelial sodium channel beta subunit. (15856328)
2005
18
A novel epithelial sodium channel beta-subunit mutation associated with hypertensive Liddle syndrome. (15690192)
2005
19
Distinction between Liddle syndrome and apparent mineralocorticoid excess. (14625721)
2004
20
Dysfunction of the epithelial sodium channel expressed in the kidney of a mouse model for Liddle syndrome. (12937297)
2003
21
The distinction between Liddle syndrome and apparent mineralocorticoid excess. (12759812)
2003
22
Liddle syndrome in a newborn infant. (12185466)
2002
23
A frameshift mutation of beta subunit of epithelial sodium channel in a case of isolated Liddle syndrome. (12473861)
2002
24
Liddle syndrome: genetics and mechanisms of Na+ channel defects. (11780687)
2001
25
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
26
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
27
The diagnosis of Liddle syndrome by identification of a mutation in the beta subunit of the epithelial sodium channel. (9643296)
1998
28
Mutations causing Liddle syndrome reduce sodium-dependent downregulation of the epithelial sodium channel in the Xenopus oocyte expression system. (9637708)
1998
29
Liddle syndrome: an autosomal dominant form of human hypertension. (9452995)
1998
30
The ENaC channel as the primary determinant of two human diseases: Liddle syndrome and pseudohypoaldosteronism. (8987044)
1996
31
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
32
Cell surface expression of the epithelial Na channel and a mutant causing Liddle syndrome: a quantitative approach. (8986818)
1996
33
Hypertension caused by a truncated epithelial sodium channel gamma subunit: genetic heterogeneity of Liddle syndrome. (7550319)
1995
34
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
35
Liddle syndrome: clinical and cellular abnormalities. (8027210)
1994
36
Liddle syndrome: sodium influx into RBC. (7365623)
1980
37
Liddle syndrome. (480019)
1979

Variations for Liddle Syndrome

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

68
id Symbol AA change Variation ID SNP ID
1SCNN1Bp.Pro616LeuVAR_007128rs387906402
2SCNN1Bp.Pro616SerVAR_007129
3SCNN1Bp.Pro617SerVAR_026520rs137852708
4SCNN1Bp.Pro618ArgVAR_026521
5SCNN1Bp.Tyr620HisVAR_026522rs137852707

Clinvar genetic disease variations for Liddle Syndrome:

5
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:

idSuper pathwaysScoreTop Affiliating Genes
1
Show member pathways
9.6SCNN1A, SCNN1B, SCNN1G
29.3CFTR, SCNN1A, SCNN1B, SCNN1G
3
Show member pathways
9.2CYP11B2, NR3C2, REN
49.0CFTR, NEDD4, SCNN1A, SCNN1B, SCNN1G
5
Show member pathways
9.0CFTR, NEDD4, SCNN1A, SCNN1B, SCNN1G
6
Show member pathways
8.7NEDD4L, SCNN1A, SCNN1B, SCNN1G, SGK1
78.7NEDD4L, SCNN1A, SCNN1B, SCNN1G, SGK1
8
Show member pathways
8.3CFTR, NEDD4L, SCNN1A, SCNN1B, SCNN1G, SGK1
97.8HSD11B2, NEDD4L, NR3C2, SCNN1A, SCNN1B, SCNN1G

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:003470610.2SCNN1A, SCNN1B, SCNN1G
2apical plasma membraneGO:00163249.3CFTR, SCNN1A, SCNN1B, SCNN1G

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

(show all 18)
idNameGO IDScoreTop Affiliating Genes
1regulation of potassium ion transmembrane transporter activityGO:190101610.4NEDD4, NEDD4L
2negative regulation of sodium ion transmembrane transporter activityGO:200065010.4NEDD4, NEDD4L
3multicellular organismal water homeostasisGO:005089110.1SCNN1A, SCNN1B, SCNN1G
4glucocorticoid receptor signaling pathwayGO:004292110.1NEDD4, NR3C1
5sensory perception of tasteGO:005090910.1SCNN1A, SCNN1B, SCNN1G
6excretionGO:000758810.1NEDD4L, SCNN1B, SCNN1G
7cellular sodium ion homeostasisGO:000688310.1NEDD4L, SGK1
8sodium ion transmembrane transportGO:003572510.0SCNN1A, SCNN1B, SCNN1G
9glucocorticoid mediated signaling pathwayGO:004340210.0NR3C1, SGK1
10protein K63-linked ubiquitinationGO:00705349.9NEDD4, PARK2
11positive regulation of dendrite extensionGO:19038619.7NEDD4L, PARK2
12regulation of blood volume by renal aldosteroneGO:00020179.6CYP11B2, HSD11B2
13sodium ion transportGO:00068149.4NEDD4L, SCNN1B, SCNN1G, SGK1
14protein monoubiquitinationGO:00065139.4NEDD4, NEDD4L, PARK2
15sodium ion homeostasisGO:00550789.3CYP11B2, SCNN1A, SCNN1B, SCNN1G
16positive regulation of protein catabolic processGO:00457329.1NEDD4, NEDD4L, PARK2
17protein ubiquitination involved in ubiquitin-dependent protein catabolic processGO:00427879.1NEDD4, NEDD4L, PARK2
18ion transmembrane transportGO:00342208.7NEDD4L, SCNN1A, SCNN1B, SCNN1G, SGK1

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

(show all 7)
idNameGO IDScoreTop Affiliating Genes
1sodium channel inhibitor activityGO:001987110.2NEDD4, NEDD4L
2ligand-gated sodium channel activityGO:001528010.0SCNN1A, SCNN1B, SCNN1G
3sodium channel regulator activityGO:00170809.8NEDD4L, SGK1
4chloride channel regulator activityGO:00170819.7CFTR, SGK1
5potassium channel regulator activityGO:00154599.6NEDD4L, SGK1
6WW domain bindingGO:00506999.5SCNN1A, SCNN1B, SCNN1G
7steroid bindingGO:00054969.2HSD11B2, NR3C1, NR3C2

Sources for Liddle Syndrome

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2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
25GTR
26HGMD
27HMDB
28ICD10
29ICD10 via Orphanet
30ICD9CM
31IUPHAR
32KEGG
35MedGen
37MeSH
38MESH via Orphanet
39MGI
42NCI
43NCIt
44NDF-RT
47NINDS
48Novoseek
50OMIM
51OMIM via Orphanet
55PubMed
56QIAGEN
61SNOMED-CT via Orphanet
65Tumor Gene Family of Databases
66UMLS
67UMLS via Orphanet