LIWAS
MCID: LNG113
MIFTS: 30

Liang-Wang Syndrome (LIWAS)

Categories: Bone diseases, Genetic diseases, Mental diseases, Neuronal diseases
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Aliases & Classifications for Liang-Wang Syndrome

MalaCards integrated aliases for Liang-Wang Syndrome:

Name: Liang-Wang Syndrome 57 73 28 5 38
Liwas 57 73

Characteristics:


Inheritance:

Autosomal dominant 57

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
onset in infancy
highly variable phenotype
de novo mutation
highly variable severity
patients with type a phenotype have the most severe disorder with multisystem involvement (last curated january 2020)


Classifications:



Summaries for Liang-Wang Syndrome

OMIM®: 57 Liang-Wang syndrome (LIWAS) is a polymalformation syndrome apparent from birth that shows large phenotypic variability and severity. However, all patients have some degree of neurologic dysfunction. The most severely affected individuals have severe global developmental delay with impaired intellectual development and poor or absent speech, marked craniofacial dysmorphism, and visceral and connective tissue abnormalities affecting the bones and vessels. The least severely affected individuals lack seizures, significant dysmorphism, and visceral involvement; they come to attention for neurologic signs and symptoms, including developmental delay with speech delay, strabismus, and/or ataxia. About half of patients have brain imaging anomalies, notably cerebral and cerebellar atrophy and thin corpus callosum, whereas the other half have normal brain imaging (summary by Liang et al., 2019). (618729) (Updated 08-Dec-2022)

MalaCards based summary: Liang-Wang Syndrome, also known as liwas, is related to neonatal diabetes and paroxysmal dystonia. An important gene associated with Liang-Wang Syndrome is KCNMA1 (Potassium Calcium-Activated Channel Subfamily M Alpha 1). Affiliated tissues include brain, bone and tongue, and related phenotypes are nystagmus and ataxia

UniProtKB/Swiss-Prot: 73 An autosomal dominant syndrome characterized by a highly variable phenotype and severity. The broad spectrum of clinical features includes developmental delay, intellectual disability, ataxia, axial hypotonia, and poor or absent speech, visceral and cardiac malformations, connective tissue presentations with arterial involvement, bone dysplasia and characteristic craniofacial dysmorphism. About half of patients have cerebral and cerebellar atrophy, and thin corpus callosum.

Related Diseases for Liang-Wang Syndrome

Diseases related to Liang-Wang Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 neonatal diabetes 10.1
2 paroxysmal dystonia 10.1
3 paroxysmal dyskinesia 10.1
4 paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy 9.5 KCNMA1-AS1 KCNMA1

Symptoms & Phenotypes for Liang-Wang Syndrome

Human phenotypes related to Liang-Wang Syndrome:

30 (show all 24)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nystagmus 30 Very rare (1%) HP:0000639
2 ataxia 30 Very rare (1%) HP:0001251
3 macroglossia 30 Very rare (1%) HP:0000158
4 gingival overgrowth 30 Very rare (1%) HP:0000212
5 hypertelorism 30 Very rare (1%) HP:0000316
6 wide nasal bridge 30 Very rare (1%) HP:0000431
7 delayed speech and language development 30 Very rare (1%) HP:0000750
8 everted lower lip vermilion 30 Very rare (1%) HP:0000232
9 strabismus 30 Very rare (1%) HP:0000486
10 downslanted palpebral fissures 30 Very rare (1%) HP:0000494
11 downturned corners of mouth 30 Very rare (1%) HP:0002714
12 laryngomalacia 30 Very rare (1%) HP:0001601
13 thin upper lip vermilion 30 Very rare (1%) HP:0000219
14 wide mouth 30 Very rare (1%) HP:0000154
15 megalocornea 30 Very rare (1%) HP:0000485
16 dystonia 30 Very rare (1%) HP:0001332
17 synophrys 30 Very rare (1%) HP:0000664
18 cerebellar atrophy 30 Very rare (1%) HP:0001272
19 status epilepticus 30 Very rare (1%) HP:0002133
20 cerebral atrophy 30 Very rare (1%) HP:0002059
21 generalized non-motor (absence) seizure 30 Very rare (1%) HP:0002121
22 diastema 30 Very rare (1%) HP:0000699
23 macrodontia of permanent maxillary central incisor 30 Very rare (1%) HP:0000675
24 axial hypotonia 30 Very rare (1%) HP:0008936

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Head And Neck Eyes:
nystagmus
hypertelorism
strabismus
downslanting palpebral fissures

Head And Neck Face:
coarse facial features
craniofacial dysmorphism, severe (phenotypic group a)

Cardiovascular Vascular:
aortic aneurysm
vascular ectasia
vascular tortuosity, intracranial and aortic (group a)

Head And Neck Nose:
broad nasal root

Head And Neck Ears:
sensorineural deafness (1 patient)

Abdomen Gastrointestinal:
pseudoobstruction (group a)
intestinal atresia (group a)
intestinal dilatation (group a)
malrotation (group a)

Skeletal:
increased bone density (group a)
dysplastic bones, axial and appendicular (group a)
sclerosing dysplasia (group a)

Skin Nails Hair Skin:
hemangioma (group a)

Neurologic Central Nervous System:
ataxia
tremor
cerebellar atrophy
cerebral atrophy
speech apraxia
more
Head And Neck Mouth:
wide mouth
thin upper lip
downturned corners of the mouth
gingival hyperplasia
thick everted lower lip
more
Muscle Soft Tissue:
axial hypotonia

Neurologic Behavioral Psychiatric Manifestations:
autistic features (1 patient)

Chest Ribs Sternum Clavicles And Scapulae:
enlarged ribs (group a)

Genitourinary Bladder:
enlarged bladder (group a)

Skeletal Skull:
thickened skull base (group a)

Skin Nails Hair Hair:
hirsutism (group a)

Clinical features from OMIM®:

618729 (Updated 08-Dec-2022)

Drugs & Therapeutics for Liang-Wang Syndrome

Search Clinical Trials, NIH Clinical Center for Liang-Wang Syndrome

Genetic Tests for Liang-Wang Syndrome

Genetic tests related to Liang-Wang Syndrome:

# Genetic test Affiliating Genes
1 Liang-Wang Syndrome 28 KCNMA1

Anatomical Context for Liang-Wang Syndrome

Organs/tissues related to Liang-Wang Syndrome:

MalaCards : Brain, Bone, Tongue

Publications for Liang-Wang Syndrome

Articles related to Liang-Wang Syndrome:

(show all 16)
# Title Authors PMID Year
1
De novo loss-of-function KCNMA1 variants are associated with a new multiple malformation syndrome and a broad spectrum of developmental and neurological phenotypes. 57 5
31152168 2019
2
Cerebellar ataxia and Purkinje cell dysfunction caused by Ca2+-activated K+ channel deficiency. 57 5
15194823 2004
3
Loss-of-function BK channel mutation causes impaired mitochondria and progressive cerebellar ataxia. 5
32132200 2020
4
Autozygosity reveals recessive mutations and novel mechanisms in dominant genes: implications in variant interpretation. 5
28383543 2017
5
Homozygous KCNMA1 mutation as a cause of cerebellar atrophy, developmental delay and seizures. 5
27567911 2016
6
De novo KCNMA1 mutations in children with early-onset paroxysmal dyskinesia and developmental delay. 5
26195193 2015
7
Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder. 5
15937479 2005
8
Overactive bladder and incontinence in the absence of the BK large conductance Ca2+-activated K+ channel. 5
15184377 2004
9
Early-onset absence epilepsy and paroxysmal dyskinesia. 5
12366739 2002
10
The long and winding road to personalized medicine in KCNMA1-linked channelopathies revealed by novel variants associated with the Liang-Wang syndrome. 62
35730691 2022
11
Identification and functional analysis of two new de novo KCNMA1 variants associated with Liang-Wang syndrome. 62
35156297 2022
12
Neonatal Diabetes in Patients Affected by Liang-Wang Syndrome Carrying KCNMA1 Variant p.(Gly375Arg) Suggest a Potential Role of Ca2+ and Voltage-Activated K+ Channel Activity in Human Insulin Secretion. 62
34563042 2021
13
Ticks (Ixodoidea) of domestic animals in Iraq. 5. Infestations in the Liwas of Diwaniya and Nasiriya (spring), Karbala (winter), and Hilla (autumn and winter). 62
5807852 1969
14
Ticks (Ixodoidea) of domestic animals in Iraq. 3. Autumn infestations in the Liwas of Kut, Amara and Basra; winter and summer infestations in the Liwa of Baghdad. 62
5690608 1968
15
Ticks (Ixodoidea) of domestic animals in Iraq. 2. Summer infestations in the Liwas of Hilla, Karbala, Diwaniya and Nasiriya. 62
5642174 1968
16
Ticks (Ixodoidea) of domestic animals in Iraq. Spring and early summer infestations in the Liwas of Baghdad, Kut, Amara, and Basra. 62
6069350 1967

Variations for Liang-Wang Syndrome

ClinVar genetic disease variations for Liang-Wang Syndrome:

5 (show all 15)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 KCNMA1 NM_001161352.2(KCNMA1):c.1052C>A (p.Ser351Tyr) SNV Pathogenic
804292 GRCh37: 10:78870010-78870010
GRCh38: 10:77110252-77110252
2 KCNMA1-AS1, KCNMA1 NM_001161352.2(KCNMA1):c.3022G>A (p.Asp1008Asn) SNV Pathogenic
978933 rs2049489016 GRCh37: 10:78669849-78669849
GRCh38: 10:76910091-76910091
3 KCNMA1 NM_001161352.2(KCNMA1):c.1987A>G (p.Ile663Val) SNV Pathogenic
916048 rs2092522027 GRCh37: 10:78778799-78778799
GRCh38: 10:77019041-77019041
4 KCNMA1 NM_001161352.2(KCNMA1):c.1123G>A (p.Gly375Arg) SNV Likely Pathogenic
521128 rs1554829003 GRCh37: 10:78869939-78869939
GRCh38: 10:77110181-77110181
5 KCNMA1-AS1, KCNMA1 NM_001161352.2(KCNMA1):c.2588C>T (p.Pro863Leu) SNV Likely Pathogenic
975413 rs150678882 GRCh37: 10:78709021-78709021
GRCh38: 10:76949263-76949263
6 KCNMA1 NM_001161352.2(KCNMA1):c.1334+1G>T SNV Likely Pathogenic
1526134 GRCh37: 10:78850157-78850157
GRCh38: 10:77090399-77090399
7 KCNMA1 NM_001161352.2(KCNMA1):c.379-114292C>G SNV Uncertain Significance
1679731 GRCh37: 10:79278073-79278073
GRCh38: 10:77518315-77518315
8 KCNMA1-AS1, KCNMA1 NM_001161352.2(KCNMA1):c.2594G>A (p.Arg865His) SNV Uncertain Significance
1684501 GRCh37: 10:78709015-78709015
GRCh38: 10:76949257-76949257
9 KCNMA1-AS1, KCNMA1 NM_001161352.2(KCNMA1):c.2312G>A (p.Arg771Gln) SNV Uncertain Significance
1683547 GRCh37: 10:78729780-78729780
GRCh38: 10:76970022-76970022
10 KCNMA1-AS1, KCNMA1 NM_001161352.2(KCNMA1):c.3147+6T>C SNV Uncertain Significance
947681 rs558650814 GRCh37: 10:78669718-78669718
GRCh38: 10:76909960-76909960
11 KCNMA1 NM_001161352.2(KCNMA1):c.1224-326G>C SNV Uncertain Significance
1696505 GRCh37: 10:78850594-78850594
GRCh38: 10:77090836-77090836
12 KCNMA1-AS1, KCNMA1 NM_001161352.2(KCNMA1):c.2547C>A (p.Asp849Glu) SNV Uncertain Significance
1696557 GRCh37: 10:78709062-78709062
GRCh38: 10:76949304-76949304
13 KCNMA1 NM_001161352.2(KCNMA1):c.379-51304del DEL Uncertain Significance
1696560 GRCh37: 10:79215085-79215085
GRCh38: 10:77455327-77455327
14 KCNMA1-AS1, KCNMA1 NM_001161352.2(KCNMA1):c.2282C>T (p.Pro761Leu) SNV Uncertain Significance
1191330 rs771363378 GRCh37: 10:78729810-78729810
GRCh38: 10:76970052-76970052
15 KCNMA1 NM_001161352.2(KCNMA1):c.687C>T (p.Phe229=) SNV Benign
129328 rs1131824 GRCh37: 10:78944590-78944590
GRCh38: 10:77184832-77184832

UniProtKB/Swiss-Prot genetic disease variations for Liang-Wang Syndrome:

73
# Symbol AA change Variation ID SNP ID
1 KCNMA1 p.Gly375Arg VAR_083554 rs1554829003

Expression for Liang-Wang Syndrome

Search GEO for disease gene expression data for Liang-Wang Syndrome.

Pathways for Liang-Wang Syndrome

GO Terms for Liang-Wang Syndrome

Sources for Liang-Wang Syndrome

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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