LIDLS
MCID: LDD002
MIFTS: 53

Liddle Syndrome (LIDLS) malady

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

Aliases & Classifications for Liddle Syndrome

About this section
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

About this section
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 Array, Array and Array. An important gene associated with Liddle Syndrome is SCNN1B (Sodium Channel Epithelial 1 Beta Subunit), and among its related pathways are Taste transduction and Tight junction. Affiliated tissues include heart, kidney and brain, and related mouse phenotypes are digestive/alimentary and normal.

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...

UniProtKB/Swiss-Prot:70 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 37)
idRelated DiseaseScoreTop Affiliating Genes
1liddle syndrome, scnn1b-related11.8
2liddle syndrome, scnn1g-related11.8
3gitelman syndrome10.9
4lyz-related familial visceral amyloidosis10.3SCNN1B, SCNN1G
5lztfl1- related bardet-biedl syndrome10.3SCNN1B, SCNN1G
6hyperuricemic nephropathy, familial juvenile 110.2CFTR, SCNN1B
7malignant biphasic mesothelioma10.1REN, SCNN1B, SCNN1G
8pertussis10.1CFTR, SCNN1G
9fasciitis10.1CFTR, SCNN1A, SCNN1B
10bickerstaff brainstem encephalitis10.0CFTR, SCNN1A, SCNN1B, SCNN1G
11dystonia 2510.0NR3C2, REN
12squamous blepharitis10.0CFTR, SCNN1G
13clear cell acanthoma10.0HSD11B2, REN
14hypogonadism mitral valve prolapse mental retardation10.0CYP11B2, REN
15hyperaldosteronism, familial, type iii10.0NR3C2, REN, SCNN1B, SCNN1G
16pulmonary sarcoidosis10.0NR3C2, SCNN1A, SCNN1B, SCNN1G
17clubfoot, congenital, with or without deficiency of long bones and/or mirror-image polydactyly9.9NR3C1, NR3C2
18prostate neuroendocrine neoplasm9.9HSD11B2, NR3C2, REN
19apparent mineralocorticoid excess9.9
20hyperlysinemia9.9CFTR, SCNN1A, SCNN1B, SGK1
21aorta angiosarcoma9.9HSD11B2, NR3C2, REN
22panuveitis9.8CYP11B2, NR3C2, REN
23immune system organ benign neoplasm9.8CYP11B2, NR3C2, REN
24clear cell adenocarcinoma9.8CYP11B2, NR3C2, REN
25splenic tuberculosis9.8HSD11B2, NR3C1, NR3C2
26critical limb ischemia9.7CYP11B2, NR3C2, REN
27pseudohypoaldosteronism9.7
28microphthalmia, isolated, with coloboma 79.7CYP11B2, NR3C2, REN, SCNN1G
29cataract 21, multiple types9.7HSD11B2, NR3C1, NR3C2, REN
30smith-mccort dysplasia 29.7NR3C2, REN, SCNN1A, SCNN1B, SCNN1G, SGK1
31lymphoproliferative syndrome 29.7NR3C2, REN, SCNN1A, SCNN1B, SCNN1G, SGK1
32familial nasal acilia9.6CYP11B2, HSD11B2, NR3C2, REN
33hypoaldosteronism, congenital, due to cmo i deficiency9.4CYP11B2, HSD11B2, NR3C1, NR3C2, REN
34merkel cell carcinoma9.4CYP11B2, HSD11B2, NR3C1, NR3C2, REN
35esophagus squamous cell papilloma9.4CYP11B2, HSD11B2, NR3C1, NR3C2, REN
36hypertension, essential9.3CYP11B2, HSD11B2, NEDD4L, NR3C1, NR3C2, REN
37bronchiectasis with or without elevated sweat chloride 38.4ASIC5, CFTR, CYP11B2, HSD11B2, NEDD4, NEDD4L

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



Diseases related to liddle syndrome

Symptoms & Phenotypes for Liddle Syndrome

About this section

Symptoms by clinical synopsis from OMIM:

177200

Clinical features from OMIM:

177200

Human phenotypes related to Liddle Syndrome:

 54 64 (show all 12)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 renal insufficiency64 54 Frequent (79-30%) HP:0000083
2 nephropathy64 54 Frequent (79-30%) HP:0000112
3 hypertension64 54 Very frequent (99-80%) HP:0000822
4 muscle weakness64 54 Frequent (79-30%) HP:0001324
5 constipation64 54 Very frequent (99-80%) HP:0002019
6 cerebral ischemia64 54 Frequent (79-30%) HP:0002637
7 hypokalemia64 54 Very frequent (99-80%) HP:0002900
8 arrhythmia64 54 Very frequent (99-80%) HP:0011675
9 fatigue64 54 Frequent (79-30%) HP:0012378
10 hypokalemic alkalosis64 HP:0001949
11 decreased circulating renin level64 HP:0003351
12 decreased circulating aldosterone level64 HP:0004319

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:00028738.3CFTR, HSD11B2, NR3C1, REN, SCNN1A, SCNN1B
3MP:00053888.1CFTR, NEDD4L, NR3C1, SCNN1A, SCNN1B, SCNN1G
4MP:00053858.1CYP11B2, HSD11B2, NEDD4L, NR3C1, NR3C2, REN
5MP:00053868.0CFTR, HSD11B2, NEDD4L, NR3C1, NR3C2, REN
6MP:00107687.6CFTR, 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

About this section

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

About this section

Genetic tests related to Liddle Syndrome:

id Genetic test Affiliating Genes
1 Pseudoprimary Hyperaldosteronism27

Anatomical Context for Liddle Syndrome

About this section

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

About this section

Articles related to Liddle Syndrome:

(show all 40)
idTitleAuthorsYear
1
Management of Liddle Syndrome in Pregnancy: A Case Report and Literature Review. (28396810)
2017
2
Liddle syndrome in a Turkish family with heterogeneous phenotypes. (27325428)
2016
3
Liddle syndrome: clinical and genetic profiles. (27896928)
2016
4
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
5
In Liddle Syndrome, Epithelial Sodium Channel Is Hyperactive Mainly in the Early Part of the Aldosterone-Sensitive Distal Nephron. (27170740)
2016
6
Liddle syndrome phenotype in an octogenarian. (25427961)
2015
7
Prevalence of Liddle Syndrome Among Young Hypertension Patients of Undetermined Cause in a Chinese Population. (26075967)
2015
8
A case of liddle syndrome: correspondence. (24827081)
2014
9
A novel frameshift mutation of epithelial sodium channel I^-subunit leads to Liddle syndrome in an isolated case. (25378078)
2014
10
A Case of Liddle Syndrome: Author's Reply. (24827082)
2014
11
Phenotype-genotype analysis in two Chinese families with Liddle syndrome. (24474657)
2014
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
A case of Liddle Syndrome. (23307437)
2013
14
Salt-induced hypertension in a mouse model of Liddle syndrome is mediated by epithelial sodium channels in the brain. (22802227)
2012
15
Liddle syndrome in a Serbian family and literature review of underlying mutations. (21956615)
2012
16
High prevalence of liddle syndrome phenotype among hypertensive US Veterans in Northwest Louisiana. (21054772)
2010
17
Role of the UPS in Liddle syndrome. (19007435)
2008
18
A novel epithelial sodium channel gamma-subunit de novo frameshift mutation leads to Liddle syndrome. (17634077)
2007
19
The PY motif of ENaC, mutated in Liddle syndrome, regulates channel internalization, sorting and mobilization from subapical pool. (17605762)
2007
20
Liddle syndrome caused by P616R mutation of the epithelial sodium channel beta subunit. (15856328)
2005
21
A novel epithelial sodium channel beta-subunit mutation associated with hypertensive Liddle syndrome. (15690192)
2005
22
Distinction between Liddle syndrome and apparent mineralocorticoid excess. (14625721)
2004
23
The distinction between Liddle syndrome and apparent mineralocorticoid excess. (12759812)
2003
24
Dysfunction of the epithelial sodium channel expressed in the kidney of a mouse model for Liddle syndrome. (12937297)
2003
25
Liddle syndrome in a newborn infant. (12185466)
2002
26
A frameshift mutation of beta subunit of epithelial sodium channel in a case of isolated Liddle syndrome. (12473861)
2002
27
Liddle syndrome: genetics and mechanisms of Na+ channel defects. (11780687)
2001
28
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
29
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
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 diagnosis of Liddle syndrome by identification of a mutation in the beta subunit of the epithelial sodium channel. (9643296)
1998
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
The ENaC channel as the primary determinant of two human diseases: Liddle syndrome and pseudohypoaldosteronism. (8987044)
1996
35
Cell surface expression of the epithelial Na channel and a mutant causing Liddle syndrome: a quantitative approach. (8986818)
1996
36
Hypertension caused by a truncated epithelial sodium channel gamma subunit: genetic heterogeneity of Liddle syndrome. (7550319)
1995
37
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
38
Liddle syndrome: clinical and cellular abnormalities. (8027210)
1994
39
Liddle syndrome: sodium influx into RBC. (7365623)
1980
40
Liddle syndrome. (480019)
1979

Variations for Liddle Syndrome

About this section

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, 592CinsertionPathogenic
6SCNN1BSCNN1B, 32-BP DELdeletionPathogenic
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

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
29.5CFTR, NEDD4, NEDD4L
39.3CFTR, SCNN1A, SCNN1B, SCNN1G
4
Show member pathways
9.1CYP11B2, NR3C2, REN
5
Show member pathways
9.0CFTR, NEDD4, SCNN1A, SCNN1B, SCNN1G
69.0CFTR, NEDD4, SCNN1A, SCNN1B, SCNN1G
78.9NEDD4L, SCNN1A, SCNN1B, SCNN1G, SGK1
8
Show member pathways
8.4ASIC5, NEDD4L, SCNN1A, SCNN1B, SCNN1G, SGK1
9
Show member pathways
8.0ASIC5, CFTR, NEDD4L, SCNN1A, SCNN1B, SCNN1G
107.9HSD11B2, NEDD4L, NR3C2, 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
1apical plasma membraneGO:001632410.1CFTR, SCNN1A, SCNN1B, SCNN1G
2sodium channel complexGO:00347069.6SCNN1A, SCNN1B, SCNN1G
3plasma membraneGO:00058867.5ASIC5, CFTR, NEDD4, NEDD4L, REN, SCNN1A
4membraneGO:00160206.9ASIC5, CFTR, CYP11B2, HSD11B2, NEDD4, NR3C2

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

(show all 13)
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:000758810.4NEDD4L, SCNN1B, SCNN1G
5sensory perception of tasteGO:005090910.2SCNN1A, SCNN1B, SCNN1G
6glucocorticoid receptor signaling pathwayGO:004292110.1NEDD4, NR3C1
7regulation of blood volume by renal aldosteroneGO:00020179.9CYP11B2, HSD11B2
8multicellular organismal water homeostasisGO:00508919.9CFTR, SCNN1A, SCNN1B, SCNN1G
9sodium ion transmembrane transportGO:00357259.7ASIC5, SCNN1A, SCNN1B, SCNN1G
10sodium ion homeostasisGO:00550789.6CYP11B2, SCNN1A, SCNN1B, SCNN1G
11ion transportGO:00068119.4ASIC5, CFTR, SCNN1A, SCNN1B, SCNN1G
12ion transmembrane transportGO:00342209.1ASIC5, NEDD4L, SCNN1A, SCNN1B, SCNN1G, SGK1
13sodium ion transportGO:00068148.4ASIC5, 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:001545910.2NEDD4L, SGK1
3chloride channel regulator activityGO:001708110.2CFTR, SGK1
4sodium channel regulator activityGO:001708010.2NEDD4L, SGK1
5ligand-gated sodium channel activityGO:00152809.7ASIC5, SCNN1A, SCNN1B, SCNN1G
6WW domain bindingGO:00506999.6SCNN1A, SCNN1B, SCNN1G
7steroid bindingGO:00054969.1HSD11B2, NR3C1, NR3C2

Sources for Liddle Syndrome

About this section
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