MCID: LDD002
MIFTS: 60

Liddle Syndrome malady

Cardiovascular diseases, Nephrological diseases categories

Summaries for Liddle Syndrome

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42NIH Rare Diseases, 21Genetics Home Reference, 46OMIM, 32MalaCards
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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: Liddle Syndrome, also known as pseudoaldosteronism, is related to hyperaldosteronism and hypertension, 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 Mineralocorticoid biosynthesis and Class C/3 (Metabotropic glutamate/pheromone receptors). The compounds 11alpha-hydroxyprogesterone and potassium canrenoate have been mentioned in the context of this disorder. Affiliated tissues include heart, kidney and brain, and related mouse phenotypes are respiratory system and normal.

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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8Disease Ontology, 9diseasecard, 42NIH Rare Diseases, 21Genetics Home Reference, 46OMIM, 10DISEASES, 48Orphanet, 60UMLS, 34MeSH, 26ICD10 via Orphanet, 57SNOMED-CT via Orphanet, 61UMLS via Orphanet, 35MESH via Orphanet
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Classifications:

Malacards categories (disease lists): (See all malacards categories)
Anatomical: Cardiovascular diseases, Nephrological diseases


Characteristics (Orphanet epidemiological data):

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


Aliases & Descriptions:

liddle syndrome 8 9 42 21 46 10 48 60
pseudoaldosteronism 8 42 21 48
pseudoprimary hyperaldosteronism 21
pseudohyperaldosteronism type 1 48
liddle's syndrome 42


External Ids:

Disease Ontology8 DOID:0050477
MeSH34 D056929
OMIM46 177200
ICD10 via Orphanet26 I15.1
SNOMED-CT via Orphanet57 71275003
UMLS via Orphanet61 C0221043
MESH via Orphanet35 D056929

Related Diseases for Liddle Syndrome

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17GeneCards, 18GeneDecks
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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/GeneDecks gene sharing:

(show all 46)
idRelated DiseaseScoreTop Affiliating Genes
1hyperaldosteronism30.7HSD11B2, NR3C2, CYP11B2, REN
2hypertension30.6HSD11B2, SCNN1B, SCNN1A, SCNN1G, NEDD4L, NR3C2
3apparent mineralocorticoid excess syndrome30.3HSD11B2, NR3C2
4pseudohypoaldosteronism30.0ASIC5, CFTR, WNK4, REN, NR3C2, NEDD4
5hypokalemia30.0HSD11B2, NR3C2, NR3C1, CYP11B2, REN
6liddle syndrome, scnn1b-related10.2
7liddle syndrome, scnn1g-related10.2
8hypophosphatemia10.0
9gitelman syndrome10.0
10pneumonia10.0
11bronchiectasis with or without elevated sweat chloride 110.0SCNN1B
12bronchiectasis10.0CFTR
13cholera10.0CFTR
14pseudohypoaldosteronism type ii10.0WNK4
15atherosclerosis10.0NR3C2
16nephrotic syndrome10.0NR3C1
17autosomal recessive pseudohypoaldosteronism type 110.0SCNN1A, SCNN1B
18cystic fibrosis10.0ASIC5, CFTR
19hypoaldosteronism10.0REN, CYP11B2
20pseudohypoaldosteronism type 110.0SCNN1B, SCNN1A, SCNN1G
21polycystic ovary syndrome10.0NR3C2
22sinusitis10.0CFTR
23respiratory failure10.0CFTR
24addison's disease10.0REN, CYP11B2
25low renin hypertension10.0REN, CYP11B2, HSD11B2
26pure autonomic failure10.0NEDD4L, REN
27adrenal adenoma10.0HSD11B2, CYP11B2, REN
28ocular hypertension10.0NR3C1
29conn's syndrome10.0NR3C2, CYP11B2, REN
30congenital adrenal hyperplasia10.0NR3C1, CYP11B2, REN
31congestive heart failure10.0REN, CYP11B2, NR3C2
32cushing's syndrome10.0REN, CYP11B2, NR3C1, HSD11B2
33metabolic acidosis10.0SCNN1G, NR3C2, REN, WNK4
34glucocorticoid-remediable aldosteronism10.0NR3C2, NR3C1, CYP11B2, REN
35adrenal gland hyperfunction10.0NR3C1, NR3C2
36primary hyperoxaluria10.0SCNN1B, NR3C2, NR3C1, REN
37chronic kidney failure10.0REN, CYP11B2, NR3C2, HSD11B2
38congenital heart defect10.0NR3C2, CYP11B2, REN, CFTR
39leukemia10.0ASIC5, CFTR, NR3C1, NR3C2
40hypertrophy of breast10.0NR3C2, CYP11B2, REN, CFTR
41pre-eclampsia10.0REN, CYP11B2, NR3C1, NR3C2, HSD11B2
42osteoporosis10.0HSD11B2, NR3C1, CFTR
43adenoma10.0REN, CYP11B2, NR3C2, HSD11B2
44proteinuria10.0HSD11B2, NR3C2, NR3C1, CYP11B2, REN, CFTR
45diabetic nephropathy10.0HSD11B2, NR3C2, REN
46essential hypertension10.0HSD11B2, NEDD4L, NR3C2, NR3C1, CYP11B2, REN

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



Diseases related to liddle syndrome

Clinical Features for Liddle Syndrome

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46OMIM, 48Orphanet
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Clinical features from OMIM:

177200

Clinical synopsis from OMIM:

177200

Symptoms:

48 (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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5CenterWatch, 41NIH Clinical Center, 6ClinicalTrials
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Approved drugs:

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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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Sources:
30LifeMap Discovery™, 32MalaCards
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MalaCards organs/tissues related to Liddle Syndrome:

32
Heart, 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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36MGI
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Publications for Liddle Syndrome

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50PubMed
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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

Genetic Variations for Liddle Syndrome

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62UniProtKB/Swiss-Prot
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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

Expression for genes affiliated with Liddle Syndrome

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1BioGPS, 15Gene 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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53Reactome, 37NCBI BioSystems Database, 29KEGG, 49PharmGKB, 51QIAGEN, 12EMD Millipore, 4Cell Signaling Technology
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Pathways related to Liddle Syndrome according to GeneCards/GeneDecks:

(show all 16)
idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Hide members
10.1CYP11B2, HSD11B2
2
Hide members
10.0SCNN1G, SCNN1A, SCNN1B
3
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9.9REN, CYP11B2, NR3C2
4
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9.8NEDD4, WWP1
5
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9.7SCNN1B, SCNN1D, SCNN1A, SCNN1G
69.7SCNN1B, SCNN1D, SCNN1A, SCNN1G
79.6SCNN1B, SCNN1A, SCNN1G, NEDD4L, WNK4
89.6UBE2S, NEDD4, NEDD4L, REN
9
NO-dependent CFTR activation (normal and CF)
9.5SCNN1B, SCNN1D, SCNN1A, SCNN1G, CFTR
109.4HSD11B2, SCNN1B, SCNN1A, SCNN1G, NEDD4L, NR3C2
11
CFTR-dependent regulation of ion channels in Airway Epithelium (norm and CF)
9.3CFTR, NEDD4, SCNN1G, SCNN1A, SCNN1D, SCNN1B
12
Hide members
9.3SCNN1B, SCNN1D, SCNN1A, SCNN1G, NEDD4, CFTR
13
Hide members
8.9WWP1, SCNN1B, SCNN1D, SCNN1A, SCNN1G, NEDD4L
14
Hide members
8.8HERC5, UBE2E3, UBE2S, WWP1, NEDD4, NEDD4L
15
Hide members
8.7WWP1, SCNN1B, SCNN1D, SCNN1A, SCNN1G, NEDD4L
16
Hide members
8.7UBE2E3, UBE2S, WWP1, NEDD4, NEDD4L, SEC24D

Compounds for genes affiliated with Liddle Syndrome

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44Novoseek, 24HMDB, 28IUPHAR, 11DrugBank, 59Tocris Bioscience, 49PharmGKB, 2BitterDB
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Compounds related to Liddle Syndrome according to GeneCards/GeneDecks:

(show top 50)    (show all 65)
idCompoundScoreTop Affiliating Genes
111alpha-hydroxyprogesterone4410.4NR3C2, HSD11B2
2potassium canrenoate4410.4NR3C1, NR3C2
3allotetrahydrocortisol4410.4HSD11B2, NR3C2
418-hydroxycorticosterone44 2411.3REN, CYP11B2
5tetrahydroaldosterone4410.3REN, CYP11B2, NR3C2
6zk11299344 2811.3NR3C2, NR3C1
7cortisone acetate44 1111.3NR3C1, HSD11B2
811-dehydrocorticosterone44 2411.3NR3C2, HSD11B2, NR3C1
9deoxycorticosterone28 2411.3NR3C1, NR3C2, CYP11B2
10tetrahydrocortisol44 2411.3HSD11B2, NR3C2
11aldosterone28 11 2412.3NR3C1, CYP11B2, NR3C2
12felodipine44 28 1112.2CFTR, NR3C2, REN
13tetrahydrocortisone44 2411.2HSD11B2, NR3C2
14metyrapone59 44 1112.2NR3C1, NR3C2, CYP11B2
15triamcinolone acetonide44 2811.2CFTR, NR3C2, NR3C1
16fluticasone propionate44 49 59 1113.2HSD11B2, NR3C1, NR3C2
17ang ii4410.2REN, CYP11B2, NR3C2
18cortisol28 2411.2NR3C1, HSD11B2, NR3C2, CYP11B2
19fludrocortisone44 28 1112.1CYP11B2, NR3C2, NR3C1, REN
20glycyrrhetinic acid44 2411.1HSD11B2, NR3C2, NR3C1, REN
21glycyrrhizin44 2811.1NR3C2, NR3C1, REN, HSD11B2
22eplerenone44 59 28 1113.1NR3C1, CYP11B2, REN, NR3C2
2311 deoxycortisol4410.1REN, CYP11B2, NR3C1, NR3C2
24cortisone44 2411.1CYP11B2, NR3C1, NR3C2, HSD11B2
25carbenoxolone28 44 1112.1HSD11B2, NR3C1, REN, NR3C2
26thiazide4410.1WNK4, NR3C2, SCNN1A, REN
27dhea4410.1HSD11B2, NR3C2, NR3C1, CYP11B2
283beta-hydroxysteroid4410.0CYP11B2, NR3C2, HSD11B2
29hydrochlorothiazide44 49 28 11 2414.0HSD11B2, NEDD4L, CYP11B2, REN, NR3C2
30doca4410.0HSD11B2, REN, CYP11B2, NR3C1, NR3C2
31spironolactone49 44 59 28 1114.0HSD11B2, NR3C2, REN, CYP11B2, NR3C1
32triamterene44 11 2412.0SCNN1B, SCNN1D, SCNN1A, NR3C2, SCNN1G
3311beta-hydroxysteroid4410.0REN, HSD11B2, CYP11B2, NR3C1, NR3C2
34corticosterone44 59 2412.0REN, CYP11B2, HSD11B2, NR3C2, NR3C1
35hydrocortisone44 2 59 1112.9NR3C2, NR3C1, HSD11B2, REN, CYP11B2
36acth449.9HSD11B2, NR3C1, CYP11B2, REN, NR3C2
37losartan44 49 28 1112.9REN, CYP11B2, NR3C2
38norepinephrine44 11 2411.9CFTR, REN, NR3C2, HSD11B2, CYP11B2
39nacl449.9ASIC5, WNK4, REN, NR3C2, SCNN1A
40actinomycin d449.8HSD11B2, SCNN1A, NR3C2, NR3C1, CFTR
41potassium44 11 2411.8CYP11B2, HSD11B2, REN, WNK4, NR3C2
42drospirenone44 49 28 1112.8REN, NR3C2
43chloride449.7WNK4, NR3C2, CFTR, REN
44dexamethasone44 49 28 1112.6NR3C2, CYP11B2, NR3C1, SCNN1A, REN, HSD11B2
45dopamine44 28 11 2412.5ASIC5, NR3C2, CFTR, REN, NR3C1
46steroid449.5NR3C1, HSD11B2, UBE2E3, NR3C2, REN, CYP11B2
47amiloride44 28 1111.4SCNN1B, SCNN1A, ASIC5, CFTR, REN, NR3C2
48Adenosine monophosphate11 2410.3UBE2S, NEDD4L, UBE2E3, NEDD4
49cysteine449.3NR3C2, NEDD4L, NEDD4, SCNN1G, UBE2E3, HSD11B2
50sodium44 248.7NEDD4, HSD11B2, UBE2E3, WWP1, ASIC5, CFTR

GO Terms for genes affiliated with Liddle Syndrome

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16Gene Ontology
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Cellular components related to Liddle Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1sodium channel complexGO:0347069.9SCNN1G, SCNN1A, SCNN1B
2apical plasma membraneGO:0163249.5SCNN1B, SCNN1A, SCNN1G, CFTR
3plasma membraneGO:0058868.3SCNN1B, SCNN1D, SCNN1A, SCNN1G, NEDD4, NEDD4L

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

(show all 17)
idNameGO IDScoreTop Affiliating Genes
1regulation of blood volume by renal aldosteroneGO:00201710.3CYP11B2, HSD11B2
2distal tubule morphogenesisGO:07215610.2WNK4, KLHL3
3ion homeostasisGO:05080110.1WNK4, KLHL3
4renal sodium ion absorptionGO:07029410.1WNK4, KLHL3
5excretionGO:00758810.1SCNN1B, SCNN1A, SCNN1G, NEDD4L
6regulation of ion transmembrane transportGO:03476510.0NEDD4L, NEDD4
7sensory perception of tasteGO:05090910.0SCNN1G, SCNN1A, SCNN1D, SCNN1B
8response to stimulusGO:05089610.0SCNN1G, SCNN1A, SCNN1D, SCNN1B
9regulation of potassium ion transmembrane transporter activityGO:19010169.9NEDD4, NEDD4L
10protein K48-linked ubiquitinationGO:0709369.9KLHL3, UBE2E3, NEDD4L
11protein K63-linked ubiquitinationGO:0705349.8UBE2E3, UBE2S, NEDD4
12sodium ion transportGO:0068149.8SCNN1B, SCNN1D, SCNN1A, SCNN1G, NEDD4L
13ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathwayGO:0431629.7NEDD4L, NEDD4
14protein ubiquitination involved in ubiquitin-dependent protein catabolic processGO:0427879.4KLHL3, HERC5, WWP1, NEDD4, NEDD4L
15protein ubiquitinationGO:0165679.4NEDD4L, NEDD4, WWP1, KLHL3
16ion transmembrane transportGO:0342209.3ASIC5, NEDD4L, SCNN1G, SCNN1A, SCNN1D, SCNN1B
17transmembrane transportGO:0550859.0WWP1, SCNN1B, SCNN1D, SCNN1A, SCNN1G, NEDD4L

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

idNameGO IDScoreTop Affiliating Genes
1WW domain bindingGO:05069910.0SCNN1G, SCNN1A, SCNN1B
2steroid bindingGO:0054969.8HSD11B2, NR3C2, NR3C1
3sodium channel inhibitor activityGO:0198719.7NEDD4L, NEDD4
4ligand-gated sodium channel activityGO:0152809.6ASIC5, SCNN1G, SCNN1A, SCNN1D, SCNN1B
5ubiquitin-protein ligase activityGO:0048428.8HERC5, UBE2E3, UBE2S, WWP1, NEDD4, NEDD4L
6protein bindingGO:0055157.6HERC5, WWP1, SCNN1B, SCNN1D, SCNN1A, SCNN1G

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
50PubMed
51QIAGEN
57SNOMED-CT via Orphanet
60UMLS
61UMLS via Orphanet