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 54 38 12 50 25 56 71 13 42 14 69
Pseudoaldosteronism 12 50 25 56 71
Pseudoprimary Hyperaldosteronism 25 29 69
Liddle's Syndrome 12 50
Pseudohyperaldosteronism Type 1 56
Liddles Syndrome 52
Lidls 71

Characteristics:

Orphanet epidemiological data:

56
liddle syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Age of death: adult;

OMIM:

54
Inheritance:
autosomal dominant (16p)


HPO:

32
liddle syndrome:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Liddle Syndrome

NIH Rare Diseases : 50 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 fatigue, muscle weakness and renal insufficiency. An important gene associated with Liddle Syndrome is SCNN1B (Sodium Channel Epithelial 1 Beta Subunit), and among its related pathways/superpathways are Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds and Neuropathic Pain-Signaling in Dorsal Horn Neurons. Affiliated tissues include Kidney, heart and kidney, and related phenotypes are behavior/neurological and homeostasis/metabolism

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 : 54
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.

Related Diseases for Liddle Syndrome

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)
id Related Disease Score Top Affiliating Genes
1 liddle syndrome, scnn1b-related 11.8
2 liddle syndrome, scnn1g-related 11.8
3 pertussis 10.5 CFTR SCNN1G
4 bronchiectasis with or without elevated sweat chloride 3 10.5 CFTR SCNN1B
5 squamous blepharitis 10.3 CFTR SCNN1G
6 rhinitis 10.3 REN SCNN1B SCNN1G
7 hyperaldosteronism 10.3
8 marden-walker syndrome 10.1 NR3C2 REN
9 mazabraud syndrome 10.0 CFTR SCNN1A SCNN1B SCNN1G
10 retinal vein occlusion 10.0 NR3C2 REN SCNN1G
11 venezuelan equine encephalitis 10.0 CFTR SCNN1A SCNN1B SCNN1G
12 clear cell acanthoma 10.0 HSD11B2 REN
13 hypodontia of incisors and premolars 9.9 CYP11B2 REN
14 pyogenic arthritis, pyoderma gangrenosum and acne 9.9 NEDD4L REN
15 apparent mineralocorticoid excess 9.9
16 branchiootorenal/branchiootic syndrome 9.9 CYP11B2 REN
17 long qt syndrome 13 9.8 NR3C2 REN SCNN1B SCNN1G
18 pulmonary fibrosis 9.8 NR3C2 SCNN1A SCNN1B SCNN1G
19 myopia 25, autosomal dominant 9.8 NR3C1 NR3C2
20 pseudohypoaldosteronism 9.7
21 adenocarcinoma 9.7 HSD11B2 NR3C2 REN
22 cutis laxa, autosomal recessive, type ia 9.6 HSD11B2 NR3C1
23 congenital bilateral absence of vas deferens 9.6 CFTR SCNN1A SCNN1B SCNN1G SGK1
24 laryngostenosis 9.5 CYP11B2 NR3C2
25 cardiovascular organ benign neoplasm 9.5 CYP11B2 NR3C2 REN
26 panuveitis 9.5 CYP11B2 NR3C2 REN
27 renal clear cell carcinoma 9.4 CYP11B2 NR3C2 REN
28 craniosynostosis 9.3 CYP11B2 NR3C2 REN
29 microphthalmia, isolated, with coloboma 7 9.2 CYP11B2 NR3C2 REN SCNN1G
30 north american indian childhood cirrhosis 9.2 HSD11B2 NR3C1 NR3C2 REN
31 hypertension, early-onset, autosomal dominant, with exacerbation in pregnancy 9.1 NR3C2 REN SCNN1A SCNN1B SCNN1G SGK1
32 bronchiectasis with or without elevated sweat chloride 2 9.1 NR3C2 REN SCNN1A SCNN1B SCNN1G SGK1
33 hypoaldosteronism, congenital, due to cmo ii deficiency 8.4 CYP11B2 HSD11B2 NR3C1 NR3C2 REN
34 trabecular follicular adenocarcinoma 8.4 CYP11B2 HSD11B2 NR3C1 NR3C2 REN
35 bronchiectasis 8.4 CYP11B2 HSD11B2 NR3C1 NR3C2 REN
36 hypertension, essential 8.1 CYP11B2 HSD11B2 NEDD4L NR3C1 NR3C2 REN
37 bronchiectasis with or without elevated sweat chloride 1 5.7 ASIC5 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

Symptoms via clinical synopsis from OMIM:

54

Renal:
renal failure
renal epithelial sodium channel defect

Endocrine:
hypertension
pseudoaldosteronism

Lab:
hypokalemia
decreased renin
hypoaldosteronism
decreased angiotensin

Metabolic:
hypokalemic alkalosis


Clinical features from OMIM:

177200

Human phenotypes related to Liddle Syndrome:

56 32 (show all 12)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 fatigue 56 32 frequent (33%) Frequent (79-30%) HP:0012378
2 muscle weakness 56 32 frequent (33%) Frequent (79-30%) HP:0001324
3 renal insufficiency 56 32 frequent (33%) Frequent (79-30%) HP:0000083
4 hypokalemia 56 32 hallmark (90%) Very frequent (99-80%) HP:0002900
5 constipation 56 32 hallmark (90%) Very frequent (99-80%) HP:0002019
6 hypertension 56 32 hallmark (90%) Very frequent (99-80%) HP:0000822
7 arrhythmia 56 32 hallmark (90%) Very frequent (99-80%) HP:0011675
8 nephropathy 56 32 frequent (33%) Frequent (79-30%) HP:0000112
9 cerebral ischemia 56 32 frequent (33%) Frequent (79-30%) HP:0002637
10 hypokalemic alkalosis 32 HP:0001949
11 decreased circulating aldosterone level 32 HP:0004319
12 decreased circulating renin level 32 HP:0003351

MGI Mouse Phenotypes related to Liddle Syndrome:

44
id 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 NEDD4L NR3C1 NR3C2 REN SCNN1A SCNN1B
3 growth/size/body region MP:0005378 10.02 CFTR CYP11B2 NR3C1 NR3C2 REN SCNN1A
4 cardiovascular system MP:0005385 9.98 CYP11B2 HSD11B2 NEDD4L NR3C1 NR3C2 REN
5 digestive/alimentary MP:0005381 9.95 CFTR HSD11B2 NEDD4L NR3C1 SCNN1A SCNN1B
6 mortality/aging MP:0010768 9.91 NR3C2 REN SCNN1A SCNN1B SCNN1G CFTR
7 normal MP:0002873 9.7 CFTR HSD11B2 NR3C1 REN SCNN1A SCNN1B
8 renal/urinary system MP:0005367 9.65 CYP11B2 HSD11B2 NEDD4L NR3C1 NR3C2 REN
9 respiratory system MP:0005388 9.1 CFTR NEDD4L NR3C1 SCNN1A SCNN1B SCNN1G

Drugs & Therapeutics for Liddle Syndrome

Interventional clinical trials:


id 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:

id Genetic test Affiliating Genes
1 Pseudoprimary Hyperaldosteronism 29

Anatomical Context for Liddle Syndrome

MalaCards organs/tissues related to Liddle Syndrome:

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

Variations for Liddle Syndrome

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

71
id 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
id 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 GeneCards Suite gene sharing:

id 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 11.86 CFTR NEDD4 NEDD4L
5
Show member pathways
11.7 SCNN1A SCNN1B SCNN1G
6 11.1 CFTR NEDD4 SCNN1A SCNN1B SCNN1G
7 10.82 NEDD4L SCNN1A SCNN1B SCNN1G SGK1
8 10.74 HSD11B2 NEDD4L NR3C2 SCNN1A SCNN1B SCNN1G
9 10.67 CFTR SCNN1A SCNN1B SCNN1G

GO Terms for Liddle Syndrome

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

id Name GO ID Score Top Affiliating Genes
1 plasma membrane GO:0005886 9.81 ASIC5 CFTR NEDD4 NEDD4L REN SCNN1A
2 apical plasma membrane GO:0016324 9.26 CFTR SCNN1A SCNN1B SCNN1G
3 sodium channel complex GO:0034706 8.8 SCNN1A SCNN1B SCNN1G
4 membrane GO:0016020 10 ASIC5 CFTR CYP11B2 HSD11B2 NEDD4 NR3C2

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

(show all 13)
id 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 negative regulation of sodium ion transmembrane transporter activity GO:2000650 9.48 NEDD4 NEDD4L
10 regulation of potassium ion transmembrane transporter activity GO:1901016 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:

id 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
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 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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