MCID: LDD002
MIFTS: 51

Liddle Syndrome malady

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

Aliases & Classifications for Liddle Syndrome

About this section
Sources:
49OMIM, 32LifeMap Discovery®, 10Disease Ontology, 11diseasecard, 45NIH Rare Diseases, 23Genetics Home Reference, 12DISEASES, 51Orphanet, 67UniProtKB/Swiss-Prot, 36MeSH, 65UMLS, 24GTR, 47Novoseek, 42NCIt, 59SNOMED-CT, 28ICD10 via Orphanet, 37MESH via Orphanet, 66UMLS via Orphanet, 34MedGen, 61The Human Phenotype Ontology
See all MalaCards sources

Aliases & Descriptions for Liddle Syndrome:

Name: Liddle Syndrome 49 32 10 11 45 23 12 51 67 36 65
Pseudoaldosteronism 10 45 23 51 67
Pseudoprimary Hyperaldosteronism 23 24 65
Liddle's Syndrome 10 45
 
Pseudohyperaldosteronism Type 1 51
Liddles Syndrome 47
Lidls 67

Characteristics:

Orphanet epidemiological data:

51
liddle syndrome:
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Age of death: adult

HPO:

61
liddle syndrome:
Inheritance: autosomal dominant inheritance


Classifications:



External Ids:

OMIM49 177200
Disease Ontology10 DOID:0050477
MeSH36 D056929
NCIt42 C84827
Orphanet51 526
ICD10 via Orphanet28 I15.1
MESH via Orphanet37 D056929
UMLS via Orphanet66 C0221043
MedGen34 C0221043
UMLS65 C0221043, C3854315

Summaries for Liddle Syndrome

About this section
NIH Rare Diseases:45 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 arrhythmia, hypokalemia and constipation. 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, prostate and liver, and related mouse phenotypes are respiratory system and normal.

Genetics Home Reference:23 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:49 Liddle syndrome is an autosomal dominant disorder characterized by early-onset salt-sensitive hypertension,... (177200) more...

UniProtKB/Swiss-Prot:67 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

About this section

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 35)
idRelated DiseaseScoreTop Affiliating Genes
1liddle syndrome, scnn1b-related12.0
2liddle syndrome, scnn1g-related12.0
3bronchiectasis with or without elevated sweat chloride 310.5CFTR, SCNN1B
4purpura simplex10.3NEDD4L, REN
5richter's syndrome10.2HSD11B2, REN
6hypochromic microcytic anemia with iron overload10.2CYP11B2, REN
7apparent mineralocorticoid excess10.0
8pulmonary nodular lymphoid hyperplasia10.0CFTR, SCNN1A, SCNN1B, SCNN1G
9dextrocardia9.9CFTR, SCNN1A, SCNN1B, SCNN1G
10bronchiectasis with or without elevated sweat chloride 29.9NR3C2, SCNN1A, SCNN1B, SCNN1G
11congenital bilateral absence of vas deferens9.9CFTR, SCNN1A, SCNN1B, SCNN1G
12ethmoid sinus inverted papilloma9.9CYP11B2, REN
13marden-walker syndrome9.9NR3C2, REN, WNK4
14iga glomerulonephritis9.9HSD11B2, NR3C2, REN
15pseudohypoaldosteronism9.9
16chromophobe adenocarcinoma9.8REN, SCNN1B, SCNN1G, WNK4
17male reproductive organ benign neoplasm9.8CYP11B2, REN
18paget disease of bone 49.8NR3C1, NR3C2
19sympathetic ophthalmia9.8CYP11B2, NR3C2, REN
20central nervous system organ benign neoplasm9.8CYP11B2, NR3C2, REN
21multilocular clear cell renal cell carcinoma9.7CYP11B2, NR3C2, REN
22basal cell carcinoma 79.7CYP11B2, HSD11B2
23borderline glaucoma9.6HSD11B2, NR3C1
24non-invasive bladder urothelial carcinoma9.5CYP11B2, HSD11B2, REN
25pulmonary emphysema9.4NR3C2, SCNN1A, SCNN1B, SCNN1G, WNK4
26medulloadrenal hyperfunction9.3HSD11B2, NR3C1, NR3C2
27adrenal carcinoma9.3NR3C1, NR3C2
28mitochondrial dna depletion syndrome 29.1HSD11B2, NR3C1, NR3C2, REN
29familial hyperthyroidism due to mutations in tsh receptor8.8CYP11B2, HSD11B2, NR3C2, REN, WNK4
30hypoaldosteronism, congenital, due to cmo ii deficiency8.5CYP11B2, HSD11B2, NR3C1, NR3C2, REN
31adrenal cortical adenocarcinoma8.5CYP11B2, HSD11B2, NR3C1, NR3C2, REN
32peripheral nerve schwannoma8.5CYP11B2, HSD11B2, NR3C1, NR3C2, REN
33orofaciodigital syndrome8.2CFTR, CYP11B2, HSD11B2, NR3C1, NR3C2, REN
34hypertension, essential7.8CYP11B2, HSD11B2, NEDD4L, NR3C1, NR3C2, REN
35bronchiectasis with or without elevated sweat chloride 15.9ASIC5, CFTR, CYP11B2, HSD11B2, NEDD4, NEDD4L

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



Diseases related to liddle syndrome

Symptoms for Liddle Syndrome

About this section

Symptoms by clinical synopsis from OMIM:

177200

Clinical features from OMIM:

177200

Symptoms:

 51 (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 14)
id Description Frequency HPO Source Accession
1 arrhythmia hallmark (90%) HP:0011675
2 hypokalemia hallmark (90%) HP:0002900
3 constipation hallmark (90%) HP:0002019
4 hypertension hallmark (90%) HP:0000822
5 cerebral ischemia typical (50%) HP:0002637
6 muscle weakness typical (50%) HP:0001324
7 nephropathy typical (50%) HP:0000112
8 renal insufficiency typical (50%) HP:0000083
9 hypoaldosteronism HP:0004319
10 decreased circulating renin level HP:0003351
11 hypokalemia HP:0002900
12 hypokalemic alkalosis HP:0001949
13 hypertension HP:0000822
14 renal insufficiency HP:0000083

UMLS symptoms related to Liddle Syndrome:


cushingoid facies

Drugs & Therapeutics for Liddle Syndrome

About this section

Interventional clinical trials:

idNameStatusNCT IDPhase
1The 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

About this section

Anatomical Context for Liddle Syndrome

About this section

MalaCards organs/tissues related to Liddle Syndrome:

33
Heart, Prostate, Liver, Brain, Lung, B cells, Testes

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

About this section

MGI Mouse Phenotypes related to Liddle Syndrome:

38
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053888.6CFTR, NEDD4L, NR3C1, SCNN1A, SCNN1B, SCNN1G
2MP:00028738.2CFTR, HSD11B2, NR3C1, REN, SCNN1A, SCNN1B
3MP:00053867.6CFTR, HSD11B2, NEDD4L, NR3C1, NR3C2, REN
4MP:00053787.1CFTR, CYP11B2, NR3C1, NR3C2, REN, SCNN1A
5MP:00053857.0CYP11B2, HSD11B2, NEDD4L, NR3C1, NR3C2, REN
6MP:00107687.0CFTR, HSD11B2, NEDD4L, NR3C1, NR3C2, REN
7MP:00053676.6CYP11B2, HSD11B2, NEDD4L, NR3C1, NR3C2, REN
8MP:00053766.1CFTR, CYP11B2, HSD11B2, NEDD4L, NR3C1, NR3C2

Publications for Liddle Syndrome

About this section

Articles related to Liddle Syndrome:

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

Variations for Liddle Syndrome

About this section

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

67
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:

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

About this section
Search GEO for disease gene expression data for Liddle Syndrome.

Pathways for genes affiliated with Liddle Syndrome

About this section

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
68.8NEDD4L, SCNN1A, SCNN1B, SCNN1G, WNK4
78.5HSD11B2, NEDD4L, NR3C2, SCNN1A, SCNN1B, SCNN1G
8
Show member pathways
8.0ASIC5, NEDD4L, SCNN1A, SCNN1B, SCNN1G, WNK4
9
Show member pathways
7.6ASIC5, CFTR, NEDD4L, SCNN1A, SCNN1B, SCNN1G

GO Terms for genes affiliated with Liddle Syndrome

About this section

Cellular components related to Liddle Syndrome according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1sodium channel complexGO:00347069.6SCNN1A, SCNN1B, SCNN1G

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

(show all 8)
idNameGO IDScoreTop Affiliating Genes
1regulation of potassium ion transmembrane transporter activityGO:190101610.4NEDD4, NEDD4L
2response to stimulusGO:005089610.2SCNN1A, SCNN1G
3sodium ion homeostasisGO:005507810.2SCNN1A, SCNN1B, SCNN1G
4negative regulation of sodium ion transmembrane transporter activityGO:200065010.1NEDD4, NEDD4L
5excretionGO:000758810.0NEDD4L, SCNN1B, SCNN1G
6regulation of membrane potentialGO:00423919.9NEDD4, NEDD4L
7transmembrane transportGO:00550859.0CFTR, NEDD4L, SCNN1A, SCNN1B, SCNN1G
8transcription initiation from RNA polymerase II promoterGO:00063678.8NEDD4L, NR3C1, NR3C2

Sources for Liddle Syndrome

About this section
2CDC
14ExPASy
15FDA
16FMA
24GTR
25HGMD
26HMDB
27ICD10
28ICD10 via Orphanet
29ICD9CM
30IUPHAR
31KEGG
34MedGen
36MeSH
37MESH via Orphanet
38MGI
41NCI
42NCIt
43NDF-RT
46NINDS
47Novoseek
49OMIM
50OMIM via Orphanet
54PubMed
55QIAGEN
60SNOMED-CT via Orphanet
64Tumor Gene Family of Databases
65UMLS
66UMLS via Orphanet