LIDLS
MCID: LDD002
MIFTS: 53

Liddle Syndrome (LIDLS) malady

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

Aliases & Classifications for Liddle Syndrome

Aliases & Descriptions for Liddle Syndrome:

Name: Liddle Syndrome 54 38 12 50 25 56 66 13 42 14 69
Pseudoaldosteronism 12 50 25 56 66
Pseudoprimary Hyperaldosteronism 25 29 69
Liddle's Syndrome 12 50
Pseudohyperaldosteronism Type 1 56
Liddles Syndrome 52
Lidls 66

Characteristics:

Orphanet epidemiological data:

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

HPO:

32
liddle syndrome:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 54 177200
Disease Ontology 12 DOID:0050477
MeSH 42 D056929
NCIt 47 C84827
Orphanet 56 ORPHA526
MESH via Orphanet 43 D056929
UMLS via Orphanet 70 C0221043
ICD10 via Orphanet 34 I15.1
MedGen 40 C0221043
UMLS 69 C0221043

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, scnn1g-related and liddle syndrome, scnn1b-related, 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 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,... (177200) more...

UniProtKB/Swiss-Prot : 66 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, scnn1g-related 11.8
2 liddle syndrome, scnn1b-related 11.8
3 gitelman syndrome 10.9
4 lyz-related familial visceral amyloidosis 10.3 SCNN1B SCNN1G
5 lztfl1- related bardet-biedl syndrome 10.3 SCNN1B SCNN1G
6 hyperuricemic nephropathy, familial juvenile 1 10.2 CFTR SCNN1B
7 malignant biphasic mesothelioma 10.1 REN SCNN1B SCNN1G
8 pertussis 10.1 CFTR SCNN1G
9 fasciitis 10.1 CFTR SCNN1A SCNN1B
10 bickerstaff brainstem encephalitis 10.0 CFTR SCNN1A SCNN1B SCNN1G
11 dystonia 25 10.0 NR3C2 REN
12 squamous blepharitis 10.0 CFTR SCNN1G
13 clear cell acanthoma 10.0 HSD11B2 REN
14 hypogonadism mitral valve prolapse mental retardation 10.0 CYP11B2 REN
15 hyperaldosteronism, familial, type iii 10.0 NR3C2 REN SCNN1B SCNN1G
16 pulmonary sarcoidosis 10.0 NR3C2 SCNN1A SCNN1B SCNN1G
17 clubfoot, congenital, with or without deficiency of long bones and/or mirror-image polydactyly 9.9 NR3C1 NR3C2
18 prostate neuroendocrine neoplasm 9.9 HSD11B2 NR3C2 REN
19 apparent mineralocorticoid excess 9.9
20 hyperlysinemia 9.9 CFTR SCNN1A SCNN1B SGK1
21 aorta angiosarcoma 9.9 HSD11B2 NR3C2 REN
22 panuveitis 9.8 CYP11B2 NR3C2 REN
23 immune system organ benign neoplasm 9.8 CYP11B2 NR3C2 REN
24 clear cell adenocarcinoma 9.8 CYP11B2 NR3C2 REN
25 splenic tuberculosis 9.8 HSD11B2 NR3C1 NR3C2
26 critical limb ischemia 9.7 CYP11B2 NR3C2 REN
27 pseudohypoaldosteronism 9.7
28 microphthalmia, isolated, with coloboma 7 9.7 CYP11B2 NR3C2 REN SCNN1G
29 cataract 21, multiple types 9.7 HSD11B2 NR3C1 NR3C2 REN
30 smith-mccort dysplasia 2 9.7 NR3C2 REN SCNN1A SCNN1B SCNN1G SGK1
31 lymphoproliferative syndrome 2 9.7 NR3C2 REN SCNN1A SCNN1B SCNN1G SGK1
32 familial nasal acilia 9.6 CYP11B2 HSD11B2 NR3C2 REN
33 hypoaldosteronism, congenital, due to cmo i deficiency 9.4 CYP11B2 HSD11B2 NR3C1 NR3C2 REN
34 merkel cell carcinoma 9.4 CYP11B2 HSD11B2 NR3C1 NR3C2 REN
35 esophagus squamous cell papilloma 9.4 CYP11B2 HSD11B2 NR3C1 NR3C2 REN
36 hypertension, essential 9.3 CYP11B2 HSD11B2 NEDD4L NR3C1 NR3C2 REN
37 bronchiectasis with or without elevated sweat chloride 3 8.4 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 by clinical synopsis from OMIM:

177200

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

MGI Mouse Phenotypes related to Liddle Syndrome:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.06 REN CFTR HSD11B2 NEDD4L NR3C1 NR3C2
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 CYP11B2 HSD11B2 NEDD4L NR3C1 NR3C2 REN
5 digestive/alimentary MP:0005381 9.95 SCNN1G CFTR HSD11B2 NEDD4L NR3C1 SCNN1A
6 mortality/aging MP:0010768 9.91 CFTR HSD11B2 NEDD4L NR3C1 NR3C2 REN
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
1 Juvenile Detention to Community Life Completed NCT01910324
2 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 40)
id Title Authors Year
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

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

66
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 11.88 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:

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 steroid binding GO:0005496 9.33 HSD11B2 NR3C1 NR3C2
4 chloride channel regulator activity GO:0017081 9.32 CFTR SGK1
5 sodium channel inhibitor activity GO:0019871 9.26 NEDD4 NEDD4L
6 WW domain binding GO:0050699 9.13 SCNN1A SCNN1B SCNN1G
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 Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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