MCID: LDD002
MIFTS: 53

Liddle Syndrome

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

Aliases & Classifications for Liddle Syndrome

MalaCards integrated aliases for Liddle Syndrome:

Name: Liddle Syndrome 53 37 12 72 49 24 55 71 36 13 41 14 69
Pseudoaldosteronism 53 12 49 24 55 71
Pseudoprimary Hyperaldosteronism 24 28 69
Liddle's Syndrome 12 49
Lidls 53 71
Pseudohyperaldosteronism Type 1 55
Liddles Syndrome 51

Characteristics:

Orphanet epidemiological data:

55
liddle syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Age of death: adult;

OMIM:

53
Inheritance:
autosomal dominant (16p)


HPO:

31
liddle syndrome:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 53 177200
Disease Ontology 12 DOID:0050477
MeSH 41 D056929
NCIt 46 C84827
Orphanet 55 ORPHA526
MESH via Orphanet 42 D056929
UMLS via Orphanet 70 C0221043
ICD10 via Orphanet 33 I15.1
MedGen 39 C0221043
KEGG 36 H00242

Summaries for Liddle Syndrome

NIH Rare Diseases : 49 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 diureticsĀ 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 hypokalemia and pseudohypoaldosteronism, and has symptoms including constipation, fatigue and muscle weakness. An important gene associated with Liddle Syndrome is SCNN1B (Sodium Channel Epithelial 1 Beta Subunit), and among its related pathways/superpathways are Aldosterone-regulated sodium reabsorption and Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds. Affiliated tissues include Kidney, heart and kidney, and related phenotypes are behavior/neurological and homeostasis/metabolism

OMIM : 53 Liddle syndrome is an autosomal dominant disorder characterized by early-onset salt-sensitive hypertension, hypokalemia, metabolic alkalosis, and suppression of plasma renin activity and aldosterone secretion (summary by Yang et al., 2014). Hanukoglu and Hanukoglu (2016) provided a detailed review of the ENaC gene family, including structure, function, tissue distribution, and associated inherited diseases. (177200)

UniProtKB/Swiss-Prot : 71 Liddle syndrome: An autosomal dominant disorder characterized by hypertension, hypokalemic alkalosis, and suppression of plasma renin activity and aldosterone secretion.

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.

Wikipedia : 72 Liddle\'s syndrome, also called Liddle syndrome is a genetic disorder inherited in an autosomal... more...

Related Diseases for Liddle Syndrome

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

(show all 35)
# Related Disease Score Top Affiliating Genes
1 hypokalemia 29.6 HSD11B2 NR3C2 REN
2 pseudohypoaldosteronism 29.5 NR3C2 SCNN1A SCNN1B SCNN1G
3 apparent mineralocorticoid excess 29.0 HSD11B2 NR3C1 NR3C2 REN
4 bronchiectasis with or without elevated sweat chloride 1 10.3 CFTR SCNN1B
5 miliaria rubra 10.3 CFTR SCNN1G
6 miliaria 10.2 CFTR SCNN1G
7 renal tubular transport disease 10.2 REN SCNN1B SCNN1G
8 arthrogryposis, distal, type 3 10.1 NR3C2 REN
9 bartter syndrome, type 2, antenatal 10.1 NR3C2 SCNN1B SCNN1G
10 pure autonomic failure 10.0 NEDD4L REN
11 idiopathic bronchiectasis 10.0 CFTR SCNN1A SCNN1B SCNN1G
12 renal tubular acidosis 10.0 NR3C2 REN SCNN1G
13 bronchiectasis 10.0 CFTR SCNN1A SCNN1B SCNN1G
14 steroid inherited metabolic disorder 10.0 HSD11B2 REN
15 hypoaldosteronism 9.9 CYP11B2 REN
16 metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration 9.9
17 hypophosphatemia 9.9
18 pneumonia 9.9
19 aldosterone-producing adenoma 9.9 CYP11B2 REN
20 corticosteroid-binding globulin deficiency 9.8 HSD11B2 NR3C1
21 adult syndrome 9.7 HSD11B2 NR3C1
22 anuria 9.7 HSD11B2 NR3C2 REN
23 cystic fibrosis 9.6 CFTR SCNN1A SCNN1B SCNN1G SGK1
24 pseudohypoaldosteronism, type i, autosomal recessive 9.6 NR3C2 REN SCNN1A SCNN1B SCNN1G
25 endocrine organ benign neoplasm 9.6 CYP11B2 NR3C2 REN
26 congestive heart failure 9.5 CYP11B2 NR3C2 REN
27 pseudohyperkalemia, familial, 2, due to red cell leak 9.4 CYP11B2 NR3C2 REN SCNN1G
28 hypertensive heart disease 9.4 CYP11B2 NR3C2
29 pseudohypoaldosteronism, type i, autosomal dominant 9.3 NR3C2 REN SCNN1A SCNN1B SCNN1G SGK1
30 familial hypertension 9.1 CYP11B2 HSD11B2 NR3C2 REN
31 hyperaldosteronism, familial, type i 8.8 CYP11B2 HSD11B2 NR3C1 NR3C2 REN
32 adrenal cortex disease 8.8 CYP11B2 HSD11B2 NR3C1 NR3C2 REN
33 adrenal gland disease 8.8 CYP11B2 HSD11B2 NR3C1 NR3C2 REN
34 conn's syndrome 8.8 CYP11B2 HSD11B2 NR3C1 NR3C2 REN
35 hypertension, essential 8.5 CYP11B2 HSD11B2 NEDD4L NR3C1 NR3C2 REN

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



Diseases related to Liddle Syndrome

Symptoms & Phenotypes for Liddle Syndrome

Symptoms via clinical synopsis from OMIM:

53
Endocrine:
hypertension
pseudoaldosteronism

Renal:
renal failure
renal epithelial sodium channel defect

Lab:
hypokalemia
hypoaldosteronism
decreased renin
decreased angiotensin

Metabolic:
hypokalemic alkalosis


Clinical features from OMIM:

177200

Human phenotypes related to Liddle Syndrome:

55 31 (show all 12)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 constipation 55 31 hallmark (90%) Very frequent (99-80%) HP:0002019
2 fatigue 55 31 frequent (33%) Frequent (79-30%) HP:0012378
3 muscle weakness 55 31 frequent (33%) Frequent (79-30%) HP:0001324
4 hypertension 55 31 hallmark (90%) Very frequent (99-80%) HP:0000822
5 renal insufficiency 55 31 frequent (33%) Frequent (79-30%) HP:0000083
6 nephropathy 55 31 frequent (33%) Frequent (79-30%) HP:0000112
7 hypokalemia 55 31 hallmark (90%) Very frequent (99-80%) HP:0002900
8 arrhythmia 55 31 hallmark (90%) Very frequent (99-80%) HP:0011675
9 cerebral ischemia 55 31 frequent (33%) Frequent (79-30%) HP:0002637
10 decreased circulating aldosterone level 31 HP:0004319
11 decreased circulating renin level 31 HP:0003351
12 hypokalemic alkalosis 31 HP:0001949

MGI Mouse Phenotypes related to Liddle Syndrome:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.06 CFTR HSD11B2 NEDD4L NR3C1 NR3C2 REN
2 homeostasis/metabolism MP:0005376 10.06 CFTR CYP11B2 HSD11B2 NEDD4L NR3C1 NR3C2
3 growth/size/body region MP:0005378 10.02 CFTR CYP11B2 NR3C1 NR3C2 REN SCNN1A
4 cardiovascular system MP:0005385 9.98 HSD11B2 NEDD4L NR3C1 NR3C2 REN SCNN1B
5 digestive/alimentary MP:0005381 9.95 CFTR HSD11B2 NEDD4L NR3C1 SCNN1A SCNN1B
6 mortality/aging MP:0010768 9.91 CFTR HSD11B2 NEDD4L NR3C1 NR3C2 REN
7 normal MP:0002873 9.7 REN SCNN1A SCNN1B SCNN1G CFTR HSD11B2
8 renal/urinary system MP:0005367 9.65 NEDD4L NR3C1 NR3C2 REN SCNN1A SCNN1B
9 respiratory system MP:0005388 9.1 CFTR NEDD4L NR3C1 SCNN1A SCNN1B SCNN1G

Drugs & Therapeutics for Liddle Syndrome

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 The Chinese Mutation Hotspot of ENaC Causing Liddle's Syndrome and the Association of ENaC Variations and Hypertension Suspended NCT00448162

Search NIH Clinical Center for Liddle Syndrome

Cochrane evidence based reviews: liddle syndrome

Genetic Tests for Liddle Syndrome

Genetic tests related to Liddle Syndrome:

# Genetic test Affiliating Genes
1 Pseudoprimary Hyperaldosteronism 28 SCNN1B SCNN1G

Anatomical Context for Liddle Syndrome

MalaCards organs/tissues related to Liddle Syndrome:

38
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:
# Tissue Anatomical CompartmentCell Relevance
1 Kidney Renal Collecting Duct System Collecting Duct Cells Potential therapeutic candidate, affected by disease

Publications for Liddle Syndrome

Articles related to Liddle Syndrome:

(show all 44)
# Title Authors Year
1
Three Reportedly Unrelated Families With Liddle Syndrome Inherited From a Common Ancestor. ( 29229744 )
2018
2
A Missense Mutation in the Extracellular Domain of I+ENaC Causes Liddle Syndrome. ( 28710092 )
2017
3
Liddle Syndrome in Association with Aortic Dissection. ( 28589074 )
2017
4
Genetic screening of SCNN1B and SCNN1G genes in early-onset hypertensive patients helps to identify Liddle syndrome. ( 28718682 )
2017
5
Management of Liddle Syndrome in Pregnancy: A Case Report and Literature Review. ( 28396810 )
2017
6
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
7
In Liddle Syndrome, Epithelial Sodium Channel Is Hyperactive Mainly in the Early Part of the Aldosterone-Sensitive Distal Nephron. ( 27170740 )
2016
8
Liddle syndrome in a Turkish family with heterogeneous phenotypes. ( 27325428 )
2016
9
Liddle syndrome: clinical and genetic profiles. ( 27896928 )
2016
10
Prevalence of Liddle Syndrome Among Young Hypertension Patients of Undetermined Cause in a Chinese Population. ( 26075967 )
2015
11
Liddle syndrome phenotype in an octogenarian. ( 25427961 )
2015
12
A novel frameshift mutation of epithelial sodium channel I^-subunit leads to Liddle syndrome in an isolated case. ( 25378078 )
2014
13
Phenotype-genotype analysis in two Chinese families with Liddle syndrome. ( 24474657 )
2014
14
A Case of Liddle Syndrome: Author's Reply. ( 24827082 )
2014
15
A case of liddle syndrome: correspondence. ( 24827081 )
2014
16
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
17
A case of Liddle Syndrome. ( 23307437 )
2013
18
Salt-induced hypertension in a mouse model of Liddle syndrome is mediated by epithelial sodium channels in the brain. ( 22802227 )
2012
19
Liddle syndrome in a Serbian family and literature review of underlying mutations. ( 21956615 )
2012
20
High prevalence of liddle syndrome phenotype among hypertensive US Veterans in Northwest Louisiana. ( 21054772 )
2010
21
Role of the UPS in Liddle syndrome. ( 19007435 )
2008
22
The PY motif of ENaC, mutated in Liddle syndrome, regulates channel internalization, sorting and mobilization from subapical pool. ( 17605762 )
2007
23
A novel epithelial sodium channel gamma-subunit de novo frameshift mutation leads to Liddle syndrome. ( 17634077 )
2007
24
Liddle syndrome caused by P616R mutation of the epithelial sodium channel beta subunit. ( 15856328 )
2005
25
A novel epithelial sodium channel beta-subunit mutation associated with hypertensive Liddle syndrome. ( 15690192 )
2005
26
Distinction between Liddle syndrome and apparent mineralocorticoid excess. ( 14625721 )
2004
27
Dysfunction of the epithelial sodium channel expressed in the kidney of a mouse model for Liddle syndrome. ( 12937297 )
2003
28
The distinction between Liddle syndrome and apparent mineralocorticoid excess. ( 12759812 )
2003
29
A frameshift mutation of beta subunit of epithelial sodium channel in a case of isolated Liddle syndrome. ( 12473861 )
2002
30
Liddle syndrome in a newborn infant. ( 12185466 )
2002
31
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
32
Liddle syndrome: genetics and mechanisms of Na+ channel defects. ( 11780687 )
2001
33
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
34
Mutations causing Liddle syndrome reduce sodium-dependent downregulation of the epithelial sodium channel in the Xenopus oocyte expression system. ( 9637708 )
1998
35
Liddle syndrome: an autosomal dominant form of human hypertension. ( 9452995 )
1998
36
The diagnosis of Liddle syndrome by identification of a mutation in the beta subunit of the epithelial sodium channel. ( 9643296 )
1998
37
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
38
The ENaC channel as the primary determinant of two human diseases: Liddle syndrome and pseudohypoaldosteronism. ( 8987044 )
1996
39
Cell surface expression of the epithelial Na channel and a mutant causing Liddle syndrome: a quantitative approach. ( 8986818 )
1996
40
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
41
Hypertension caused by a truncated epithelial sodium channel gamma subunit: genetic heterogeneity of Liddle syndrome. ( 7550319 )
1995
42
Liddle syndrome: clinical and cellular abnormalities. ( 8027210 )
1994
43
Liddle syndrome: sodium influx into RBC. ( 7365623 )
1980
44
Liddle syndrome. ( 480019 )
1979

Variations for Liddle Syndrome

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

71
# Symbol AA change Variation ID SNP ID
1 SCNN1B p.Pro616Leu VAR_007128 rs387906402
2 SCNN1B p.Pro616Ser VAR_007129
3 SCNN1B p.Pro617Ser VAR_026520 rs137852708
4 SCNN1B p.Pro618Arg VAR_026521 rs137852705
5 SCNN1B p.Tyr620His VAR_026522 rs137852707

ClinVar genetic disease variations for Liddle Syndrome:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 SCNN1G NM_001039.3(SCNN1G): c.1718G> A (p.Trp573Ter) single nucleotide variant Pathogenic rs137853342 GRCh37 Chromosome 16, 23226558: 23226558
2 SCNN1B NM_000336.2(SCNN1B): c.1696C> T (p.Arg566Ter) single nucleotide variant Pathogenic rs137852704 GRCh37 Chromosome 16, 23391895: 23391895
3 SCNN1B NM_000336.2(SCNN1B): c.1847C> T (p.Pro616Leu) single nucleotide variant Pathogenic rs387906402 GRCh37 Chromosome 16, 23392046: 23392046
4 SCNN1B NM_000336.2(SCNN1B): c.1858T> C (p.Tyr620His) single nucleotide variant Pathogenic rs137852707 GRCh37 Chromosome 16, 23392057: 23392057
5 SCNN1B SCNN1B, 1-BP INS, 592C insertion Pathogenic
6 SCNN1B SCNN1B, 32-BP DEL deletion Pathogenic
7 SCNN1B NM_000336.2(SCNN1B): c.1849C> T (p.Pro617Ser) single nucleotide variant Pathogenic rs137852708 GRCh37 Chromosome 16, 23392048: 23392048
8 SCNN1B NM_000336.2(SCNN1B): c.1847C> G (p.Pro616Arg) single nucleotide variant Pathogenic rs387906402 GRCh37 Chromosome 16, 23392046: 23392046

Expression for Liddle Syndrome

Search GEO for disease gene expression data for Liddle Syndrome.

Pathways for Liddle Syndrome

Pathways related to Liddle Syndrome according to KEGG:

36
# Name Kegg Source Accession
1 Aldosterone-regulated sodium reabsorption hsa04960

Pathways related to Liddle Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.08 ASIC5 CFTR NEDD4L SCNN1A SCNN1B SCNN1G
2
Show member pathways
12.36 CFTR NEDD4 SCNN1A SCNN1B SCNN1G
3
Show member pathways
12.29 ASIC5 NEDD4L SCNN1A SCNN1B SCNN1G SGK1
4 11.88 CFTR NEDD4 NEDD4L
5
Show member pathways
11.72 SCNN1A SCNN1B SCNN1G
6
Show member pathways
11.51 CYP11B2 NR3C2 REN
7 11.1 CFTR NEDD4 SCNN1A SCNN1B SCNN1G
8 10.82 NEDD4L SCNN1A SCNN1B SCNN1G SGK1
9 10.74 HSD11B2 NEDD4L NR3C2 SCNN1A SCNN1B SCNN1G
10 10.67 CFTR SCNN1A SCNN1B SCNN1G

GO Terms for Liddle Syndrome

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

# Name GO ID Score Top Affiliating Genes
1 plasma membrane GO:0005886 9.91 ASIC5 CFTR NEDD4 NEDD4L REN SCNN1A
2 membrane GO:0016020 9.9 ASIC5 CFTR CYP11B2 HSD11B2 NEDD4 NR3C2
3 apical plasma membrane GO:0016324 9.26 CFTR SCNN1A SCNN1B SCNN1G
4 sodium channel complex GO:0034706 8.8 SCNN1A SCNN1B SCNN1G

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

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 ion transport GO:0006811 9.91 ASIC5 CFTR SCNN1A SCNN1B SCNN1G
2 ion transmembrane transport GO:0034220 9.73 ASIC5 NEDD4L SCNN1A SCNN1B SCNN1G SGK1
3 sodium ion transport GO:0006814 9.63 ASIC5 NEDD4L SCNN1A SCNN1B SCNN1G SGK1
4 sodium ion transmembrane transport GO:0035725 9.62 ASIC5 SCNN1A SCNN1B SCNN1G
5 sensory perception of taste GO:0050909 9.61 SCNN1A SCNN1B SCNN1G
6 excretion GO:0007588 9.58 NEDD4L SCNN1B SCNN1G
7 protein monoubiquitination GO:0006513 9.52 NEDD4 NEDD4L
8 glucocorticoid receptor signaling pathway GO:0042921 9.49 NEDD4 NR3C1
9 regulation of potassium ion transmembrane transporter activity GO:1901016 9.48 NEDD4 NEDD4L
10 negative regulation of sodium ion transmembrane transporter activity GO:2000650 9.46 NEDD4 NEDD4L
11 regulation of blood volume by renal aldosterone GO:0002017 9.37 CYP11B2 HSD11B2
12 sodium ion homeostasis GO:0055078 9.26 CYP11B2 SCNN1A SCNN1B SCNN1G
13 multicellular organismal water homeostasis GO:0050891 8.92 CFTR SCNN1A SCNN1B SCNN1G

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

# Name GO ID Score Top Affiliating Genes
1 potassium channel regulator activity GO:0015459 9.4 NEDD4L SGK1
2 sodium channel regulator activity GO:0017080 9.37 NEDD4L SGK1
3 WW domain binding GO:0050699 9.33 SCNN1A SCNN1B SCNN1G
4 chloride channel regulator activity GO:0017081 9.32 CFTR SGK1
5 sodium channel inhibitor activity GO:0019871 9.26 NEDD4 NEDD4L
6 steroid binding GO:0005496 9.13 HSD11B2 NR3C1 NR3C2
7 ligand-gated sodium channel activity GO:0015280 8.92 ASIC5 SCNN1A SCNN1B SCNN1G

Sources for Liddle Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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