MCID: LDD002
MIFTS: 53

Liddle Syndrome malady

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

Aliases & Classifications for Liddle Syndrome

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Sources:
11Disease Ontology, 12diseasecard, 13DISEASES, 25Genetics Home Reference, 27GTR, 31ICD10 via Orphanet, 35LifeMap Discovery®, 37MedGen, 39MeSH, 40MESH via Orphanet, 45NCIt, 48NIH Rare Diseases, 50Novoseek, 52OMIM, 54Orphanet, 62SNOMED-CT, 64The Human Phenotype Ontology, 68UMLS, 69UMLS via Orphanet, 70UniProtKB/Swiss-Prot
See all MalaCards sources

Aliases & Descriptions for Liddle Syndrome:

Name: Liddle Syndrome 52 35 11 48 25 54 70 12 39 13 68
Pseudoaldosteronism 11 48 25 54 70
Pseudoprimary Hyperaldosteronism 25 27 68
Liddle's Syndrome 11 48
 
Pseudohyperaldosteronism Type 1 54
Liddles Syndrome 50
Lidls 70

Characteristics:

Orphanet epidemiological data:

54
liddle syndrome:
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Age of death: adult

HPO:

64
liddle syndrome:
Inheritance: autosomal dominant inheritance

Classifications:



External Ids:

OMIM52 177200
Disease Ontology11 DOID:0050477
MeSH39 D056929
NCIt45 C84827
Orphanet54 ORPHA526
MESH via Orphanet40 D056929
UMLS via Orphanet69 C0221043
ICD10 via Orphanet31 I15.1
MedGen37 C0221043

Summaries for Liddle Syndrome

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NIH Rare Diseases:48 Liddle syndrome is a rare, inherited condition that is primarily characterized by severe high blood pressure (hypertension) that often develops at an early age. Although the condition may not be associated with signs and symptoms initially, untreated hypertension can eventually lead to heart disease or stroke. Affected people may also have low levels of potassium in the blood (hypokalemia) and metabolic alkalosis. Liddle syndrome 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: 11/15/2016

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.

UniProtKB/Swiss-Prot:70 Liddle syndrome: An autosomal dominant disorder characterized by hypertension, hypokalemic alkalosis, and suppression of plasma renin activity and aldosterone secretion.

Genetics Home Reference:25 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:52 Liddle syndrome is an autosomal dominant disorder characterized by early-onset salt-sensitive hypertension,... (177200) more...

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 34)
idRelated DiseaseScoreTop Affiliating Genes
1liddle syndrome, scnn1b-related11.8
2liddle syndrome, scnn1g-related11.8
3gitelman syndrome10.9
4hyperuricemic nephropathy, familial juvenile 110.4CFTR, SCNN1B
5mucinous tubular and spindle renal cell carcinoma10.2REN, SCNN1B, SCNN1G
6dystonia 2510.2NR3C2, REN
7benign shuddering attacks10.0HSD11B2, REN
8paget disease of bone 410.0NR3C1, NR3C2
9aseptic osteitis10.0CFTR, SCNN1A, SCNN1B, SCNN1G
10hypodermyasis9.9CYP11B2, REN
11apparent mineralocorticoid excess9.9
12central nervous system angiosarcoma9.9HSD11B2, REN
13pulmonary fibrosis9.8NR3C2, SCNN1A, SCNN1B, SCNN1G
14neurilemmoma of the pleura9.8CYP11B2, REN
15pseudohypoaldosteronism9.7
16vestibular gland benign neoplasm9.7CYP11B2, REN
17antiphospholipid syndrome9.7HSD11B2, NR3C2, REN
18benign hypertensive renal disease9.7CYP11B2, NR3C2
19priapism9.6HSD11B2, NR3C1
20spinal canal and spinal cord meningioma9.6CFTR, CYP11B2, REN
21congenital bilateral absence of vas deferens9.6CFTR, SCNN1A, SCNN1B, SCNN1G, SGK1
22glioma susceptibility 19.6CYP11B2, HSD11B2
23cardiovascular organ benign neoplasm9.5CYP11B2, NR3C2, REN
24bronchiectasis with or without elevated sweat chloride 29.5NR3C2, SCNN1A, SCNN1B, SCNN1G, SGK1
25collecting duct carcinoma9.5CYP11B2, NR3C2, REN
26first-degree atrioventricular block9.4CYP11B2, REN
27cataract 21, multiple types9.3HSD11B2, NR3C1, NR3C2, REN
28drug-induced mental disorder9.0CYP11B2, HSD11B2, NR3C2, REN
29hypoaldosteronism, congenital, due to cmo ii deficiency8.6CYP11B2, HSD11B2, NR3C1, NR3C2, REN
30acute myocarditis8.6CYP11B2, HSD11B2, NR3C1, NR3C2, REN
31loeffler endocarditis8.6CYP11B2, HSD11B2, NR3C1, NR3C2, REN
32nasopharyngeal disease8.6CYP11B2, HSD11B2, NR3C1, NR3C2, REN
33hypertension, essential8.3CYP11B2, HSD11B2, NEDD4L, NR3C1, NR3C2, REN
34bronchiectasis with or without elevated sweat chloride 36.7CFTR, CYP11B2, HSD11B2, NEDD4, NEDD4L, NR3C1

Graphical network of the top 20 diseases related to Liddle Syndrome:



Diseases related to liddle syndrome

Symptoms & Phenotypes for Liddle Syndrome

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Symptoms by clinical synopsis from OMIM:

177200

Clinical features from OMIM:

177200

Human phenotypes related to Liddle Syndrome:

 64 54 (show all 12)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertension64 54 hallmark (90%) Very frequent (99-80%) HP:0000822
2 constipation64 54 hallmark (90%) Very frequent (99-80%) HP:0002019
3 hypokalemia64 54 hallmark (90%) Very frequent (99-80%) HP:0002900
4 arrhythmia64 54 hallmark (90%) Very frequent (99-80%) HP:0011675
5 renal insufficiency64 54 typical (50%) Frequent (79-30%) HP:0000083
6 nephropathy64 54 typical (50%) Frequent (79-30%) HP:0000112
7 muscle weakness64 54 typical (50%) Frequent (79-30%) HP:0001324
8 cerebral ischemia64 54 typical (50%) Frequent (79-30%) HP:0002637
9 hypokalemic alkalosis64 HP:0001949
10 decreased circulating renin level64 HP:0003351
11 hypoaldosteronism64 HP:0004319
12 fatigue54 Frequent (79-30%)

UMLS symptoms related to Liddle Syndrome:


cushingoid facies

MGI Mouse Phenotypes related to Liddle Syndrome according to GeneCards Suite gene sharing:

41
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053818.5CFTR, HSD11B2, NEDD4L, NR3C1, SCNN1A, SCNN1B
2MP:00028738.4CFTR, HSD11B2, NR3C1, REN, SCNN1A, SCNN1B
3MP:00053858.2CYP11B2, HSD11B2, NEDD4L, NR3C1, NR3C2, REN
4MP:00053888.1CFTR, NEDD4L, NR3C1, SCNN1A, SCNN1B, SCNN1G
5MP:00053868.0CFTR, HSD11B2, NEDD4L, NR3C1, NR3C2, REN
6MP:00107687.7CFTR, HSD11B2, NEDD4L, NR3C1, NR3C2, REN
7MP:00053787.4CFTR, CYP11B2, NR3C1, NR3C2, REN, SCNN1A
8MP:00053676.9CYP11B2, HSD11B2, NEDD4L, NR3C1, NR3C2, REN
9MP:00053766.6CFTR, CYP11B2, HSD11B2, NEDD4L, NR3C1, NR3C2

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 Hyperaldosteronism27

Anatomical Context for Liddle Syndrome

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MalaCards organs/tissues related to Liddle Syndrome:

36
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

Publications for Liddle Syndrome

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Articles related to Liddle Syndrome:

(show all 39)
idTitleAuthorsYear
1
Whole-exome sequencing reveals an inherited R566X mutation of the epithelial sodium channel I^-subunit in a case of early-onset phenotype of Liddle syndrome. (27900368)
2016
2
In Liddle Syndrome, Epithelial Sodium Channel Is Hyperactive Mainly in the Early Part of the Aldosterone-Sensitive Distal Nephron. (27170740)
2016
3
Liddle syndrome: clinical and genetic profiles. (27896928)
2016
4
Liddle syndrome in a Turkish family with heterogeneous phenotypes. (27325428)
2016
5
Prevalence of Liddle Syndrome Among Young Hypertension Patients of Undetermined Cause in a Chinese Population. (26075967)
2015
6
Liddle syndrome phenotype in an octogenarian. (25427961)
2015
7
A novel frameshift mutation of epithelial sodium channel I^-subunit leads to Liddle syndrome in an isolated case. (25378078)
2014
8
A Case of Liddle Syndrome: Author's Reply. (24827082)
2014
9
A case of liddle syndrome: correspondence. (24827081)
2014
10
Phenotype-genotype analysis in two Chinese families with Liddle syndrome. (24474657)
2014
11
A case of Liddle Syndrome. (23307437)
2013
12
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
13
Salt-induced hypertension in a mouse model of Liddle syndrome is mediated by epithelial sodium channels in the brain. (22802227)
2012
14
Liddle syndrome in a Serbian family and literature review of underlying mutations. (21956615)
2012
15
High prevalence of liddle syndrome phenotype among hypertensive US Veterans in Northwest Louisiana. (21054772)
2010
16
Role of the UPS in Liddle syndrome. (19007435)
2008
17
The PY motif of ENaC, mutated in Liddle syndrome, regulates channel internalization, sorting and mobilization from subapical pool. (17605762)
2007
18
A novel epithelial sodium channel gamma-subunit de novo frameshift mutation leads to Liddle syndrome. (17634077)
2007
19
Liddle syndrome caused by P616R mutation of the epithelial sodium channel beta subunit. (15856328)
2005
20
A novel epithelial sodium channel beta-subunit mutation associated with hypertensive Liddle syndrome. (15690192)
2005
21
Distinction between Liddle syndrome and apparent mineralocorticoid excess. (14625721)
2004
22
Dysfunction of the epithelial sodium channel expressed in the kidney of a mouse model for Liddle syndrome. (12937297)
2003
23
The distinction between Liddle syndrome and apparent mineralocorticoid excess. (12759812)
2003
24
Liddle syndrome in a newborn infant. (12185466)
2002
25
A frameshift mutation of beta subunit of epithelial sodium channel in a case of isolated Liddle syndrome. (12473861)
2002
26
Liddle syndrome: genetics and mechanisms of Na+ channel defects. (11780687)
2001
27
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
28
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
29
The diagnosis of Liddle syndrome by identification of a mutation in the beta subunit of the epithelial sodium channel. (9643296)
1998
30
Mutations causing Liddle syndrome reduce sodium-dependent downregulation of the epithelial sodium channel in the Xenopus oocyte expression system. (9637708)
1998
31
Liddle syndrome: an autosomal dominant form of human hypertension. (9452995)
1998
32
The ENaC channel as the primary determinant of two human diseases: Liddle syndrome and pseudohypoaldosteronism. (8987044)
1996
33
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
34
Cell surface expression of the epithelial Na channel and a mutant causing Liddle syndrome: a quantitative approach. (8986818)
1996
35
Hypertension caused by a truncated epithelial sodium channel gamma subunit: genetic heterogeneity of Liddle syndrome. (7550319)
1995
36
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
37
Liddle syndrome: clinical and cellular abnormalities. (8027210)
1994
38
Liddle syndrome: sodium influx into RBC. (7365623)
1980
39
Liddle syndrome. (480019)
1979

Variations for Liddle Syndrome

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

70
id Symbol AA change Variation ID SNP ID
1SCNN1Bp.Pro616LeuVAR_007128rs387906402
2SCNN1Bp.Pro616SerVAR_007129
3SCNN1Bp.Pro617SerVAR_026520rs137852708
4SCNN1Bp.Pro618ArgVAR_026521rs137852705
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)SNVPathogenicrs137853342GRCh37Chr 16, 23226558: 23226558
2SCNN1BNM_000336.2(SCNN1B): c.1696C> T (p.Arg566Ter)SNVPathogenicrs137852704GRCh37Chr 16, 23391895: 23391895
3SCNN1BNM_000336.2(SCNN1B): c.1847C> T (p.Pro616Leu)SNVPathogenicrs387906402GRCh37Chr 16, 23392046: 23392046
4SCNN1BNM_000336.2(SCNN1B): c.1858T> C (p.Tyr620His)SNVPathogenicrs137852707GRCh37Chr 16, 23392057: 23392057
5SCNN1BSCNN1B, 1-BP INS, 592CinsertionPathogenicChr na, -1: -1
6SCNN1BSCNN1B, 32-BP DELdeletionPathogenicChr na, -1: -1
7SCNN1BNM_000336.2(SCNN1B): c.1849C> T (p.Pro617Ser)SNVPathogenicrs137852708GRCh37Chr 16, 23392048: 23392048
8SCNN1BNM_000336.2(SCNN1B): c.1847C> G (p.Pro616Arg)SNVPathogenicrs387906402GRCh37Chr 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
4
Show member pathways
9.0CFTR, NEDD4, SCNN1A, SCNN1B, SCNN1G
59.0CFTR, NEDD4, SCNN1A, SCNN1B, SCNN1G
68.7NEDD4L, SCNN1A, SCNN1B, SCNN1G, SGK1
7
Show member pathways
8.2ASIC5, NEDD4L, SCNN1A, SCNN1B, SCNN1G, SGK1
87.8HSD11B2, NEDD4L, NR3C2, SCNN1A, SCNN1B, SCNN1G
9
Show member pathways
7.8ASIC5, CFTR, NEDD4L, 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
1apical plasma membraneGO:001632410.0CFTR, SCNN1A, SCNN1B, SCNN1G
2sodium channel complexGO:00347069.6SCNN1A, SCNN1B, SCNN1G
3plasma membraneGO:00058867.3ASIC5, CFTR, NEDD4, NEDD4L, REN, SCNN1A

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

(show all 14)
idNameGO IDScoreTop Affiliating Genes
1negative regulation of sodium ion transmembrane transporter activityGO:200065010.5NEDD4, NEDD4L
2protein monoubiquitinationGO:000651310.5NEDD4, NEDD4L
3regulation of potassium ion transmembrane transporter activityGO:190101610.5NEDD4, NEDD4L
4excretionGO:000758810.3NEDD4L, SCNN1B, SCNN1G
5multicellular organismal water homeostasisGO:005089110.3SCNN1A, SCNN1B, SCNN1G
6sensory perception of tasteGO:005090910.2SCNN1A, SCNN1B, SCNN1G
7cellular sodium ion homeostasisGO:000688310.2NEDD4L, SGK1
8regulation of blood volume by renal aldosteroneGO:000201710.1CYP11B2, HSD11B2
9glucocorticoid receptor signaling pathwayGO:004292110.0NEDD4, NR3C1
10sodium ion homeostasisGO:00550789.7CYP11B2, SCNN1A, SCNN1B, SCNN1G
11glucocorticoid mediated signaling pathwayGO:00434029.7NR3C1, SGK1
12sodium ion transmembrane transportGO:00357259.7ASIC5, SCNN1A, SCNN1B, SCNN1G
13sodium ion transportGO:00068149.0NEDD4L, SCNN1B, SCNN1G, SGK1
14ion transmembrane transportGO:00342208.8ASIC5, NEDD4L, 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:001987110.4NEDD4, NEDD4L
2potassium channel regulator activityGO:001545910.1NEDD4L, SGK1
3chloride channel regulator activityGO:001708110.0CFTR, SGK1
4sodium channel regulator activityGO:001708010.0NEDD4L, SGK1
5ligand-gated sodium channel activityGO:00152809.7ASIC5, SCNN1A, SCNN1B, SCNN1G
6WW domain bindingGO:00506999.6SCNN1A, SCNN1B, SCNN1G
7steroid bindingGO:00054969.2HSD11B2, NR3C1, NR3C2

Sources for Liddle Syndrome

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2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
27GTR
28HGMD
29HMDB
30ICD10
31ICD10 via Orphanet
32ICD9CM
33IUPHAR
34KEGG
37MedGen
39MeSH
40MESH via Orphanet
41MGI
44NCI
45NCIt
46NDF-RT
49NINDS
50Novoseek
52OMIM
53OMIM via Orphanet
57PubMed
58QIAGEN
63SNOMED-CT via Orphanet
67Tumor Gene Family of Databases
68UMLS
69UMLS via Orphanet