TS
MCID: TMT001
MIFTS: 55

Timothy Syndrome (TS) malady

Genetic diseases, Rare diseases categories
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Summaries for Timothy Syndrome

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NIH Rare Diseases:42 Timothy syndrome is a type of long qt syndrome. it affects many parts of the body including the heart, fingers, toes, face, and the nervous system. it is characterized by long qt syndrome, although some people with timothy syndrome also have other heart defects that affect the heart’s ability to pump blood effectively. other symptoms of timothy syndrome include fusion of the skin between fingers or toes and distinctive facial features. in addition, many children with this syndrome have developmental delay and characteristic features of autism. mental retardation and seizures can also occur in children with timothy syndrome.there are two forms of timothy syndrome. type 1 includes all of the characteristic features described. type 2 causes a more severe form of long qt syndrome and does not appear to cause fusion of skin between fingers or toes. all cases of timothy syndrome appear to be due to changes in the cacna1c gene. this syndrome is inherited in an autosomal dominant manner. however, most cases are not inherited from an affected parent, but occur for the first time in a family due to a spontaneous or random change in the cacna1c gene. last updated: 12/18/2008

MalaCards based summary: Timothy Syndrome, also known as long qt syndrome with syndactyly, is related to long qt syndrome and colorectal cancer, and has symptoms including An important gene associated with Timothy Syndrome is CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit), and among its related pathways are Translation Translation regulation by Alpha 1 adrenergic receptors and Amphetamine addiction. The compounds (+-)-bay k 8644 and nnc 55-0396 dihydrochloride have been mentioned in the context of this disorder. Affiliated tissues include heart and skin, and related mouse phenotypes are cardiovascular system and nervous system.

Disease Ontology:8 An autosomal dominant disease that is characterized by cardiac, hand/foot, facial, and neurodevelopmental features. the two forms are type 1 (classic) and type 2, a rare form caused by mutations in a transcript variant of cacna1c.

Genetics Home Reference:21 Timothy syndrome is a rare disorder that affects many parts of the body including the heart, digits (fingers and toes), and the nervous system.

Wikipedia:65 Timothy syndrome is a rare autosomal dominant disorder characterized by physical malformations, as well... more...

Description from OMIM:46 601005

GeneReviews summary for timothy

Aliases & Classifications for Timothy Syndrome

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Sources:
8Disease Ontology, 9diseasecard, 19GeneReviews, 42NIH Rare Diseases, 20GeneTests, 22GTR, 21Genetics Home Reference, 46OMIM, 10DISEASES, 48Orphanet, 62UMLS, 35MESH via Orphanet, 26ICD10 via Orphanet, 63UMLS via Orphanet
See all sources

Timothy Syndrome, Aliases & Descriptions:

Name: Timothy Syndrome 8 9 19 42 20 22 21 46 10 48 62
Long Qt Syndrome with Syndactyly 19 42 21 62
Long Qt Syndrome 8 19 42 62
Lqt8 42 21 48
 
Long Qt Syndrome - Syndactyly 48
Long Qt Syndrome Type 8 48
Ts 21


Classifications:

Malacards categories (disease lists): (See all malacards categories)
Global: Genetic diseases, Rare diseases


Characteristics (Orphanet epidemiological data):

48
timothy syndrome:
Inheritance: Autosomal dominant; Prevalence: <1/1000000


External Ids:

Disease Ontology8 DOID:0060173
OMIM46 601005
MESH via Orphanet35 C536962
ICD10 via Orphanet26 I45.8
UMLS via Orphanet63 C1832916

Related Diseases for Timothy Syndrome

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



Diseases related to timothy syndrome

Symptoms for Timothy Syndrome

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Symptoms by clinical synopsis from OMIM:

601005

Clinical features from OMIM:

601005

HPO human phenotypes related to Timothy Syndrome:

id Description Frequency HPO Source Accession
1 syndactyly HP:0001159
2 prolonged qt interval HP:0001657

Drugs & Therapeutics for Timothy Syndrome

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Drug clinical trials:

Search ClinicalTrials for Timothy Syndrome

Search NIH Clinical Center for Timothy Syndrome

Genetic Tests for Timothy Syndrome

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Genetic tests related to Timothy Syndrome:

id Genetic test Affiliating Genes
1 Timothy Syndrome20 22 CACNA1C

Anatomical Context for Timothy Syndrome

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MalaCards organs/tissues related to Timothy Syndrome:

32
Heart, Skin

Animal Models for Timothy Syndrome or affiliated genes

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MGI Mouse Phenotypes related to Timothy Syndrome:

36
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053858.1CACNA1H, CACNA1C, CACNB2, CACNA2D1, KCNE1
2MP:00036317.0CACNA1H, KCNE1, PSMC4, CACNA2D1, CACNB2, CACNA1C

Publications for Timothy Syndrome

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Articles related to Timothy Syndrome:

(show all 33)
idTitleAuthorsYear
1
Exome sequencing helped the fine diagnosis of two siblings afflicted with atypical Timothy syndrome (TS2). (24773605)
2014
2
Cellular mechanisms of ventricular arrhythmias in a mouse model of Timothy syndrome (long QT syndrome 8). (24215710)
2014
3
Dentition abnormalities in a Timothy syndrome patient with a novel genetic mutation: a case report. (24960393)
2014
4
Alteration in basal and depolarization induced transcriptional network in iPSC derived neurons from Timothy syndrome. (25360157)
2014
5
Novel Timothy syndrome mutation leading to increase in CACNA1C window current. (25260352)
2014
6
Maternal mosaicism confounds the neonatal diagnosis of type 1 Timothy syndrome. (23690510)
2013
7
Modeling Timothy syndrome with iPS cells. (23299782)
2013
8
Inhibition of late sodium current by mexiletine: a novel pharmotherapeutical approach in timothy syndrome. (23580742)
2013
9
Sudden cardiac arrest during anesthesia in a 30-month-old boy with syndactyly: a case of genetically proven Timothy syndrome. (23678275)
2013
10
Timothy syndrome is associated with activity-dependent dendritic retraction in rodent and human neurons. (23313911)
2013
11
Case scenario: anesthesia-related cardiac arrest in a child with Timothy syndrome. (23011317)
2012
12
Ca(V)1.2 I-II linker structure and Timothy syndrome. (22990809)
2012
13
Ranolazine safely decreases ventricular and atrial fibrillation in Timothy syndrome (LQT8). (20883512)
2012
14
Long QT, syndactyly, joint contractures, stroke and novel CACNA1C mutation: expanding the spectrum of Timothy syndrome. (22106044)
2012
15
L-type Ca2+ channel function during Timothy syndrome. (22999068)
2012
16
A Mouse Model of Timothy Syndrome: a Complex Autistic Disorder Resulting from a Point Mutation in Cav1.2. (24371506)
2012
17
Two mechanistically distinct effects of dihydropyridine nifedipine on CaV1.2 L-type CaA^a8_ channels revealed by Timothy syndrome mutation. (22554770)
2012
18
Mouse model of Timothy syndrome recapitulates triad of autistic traits. (21878566)
2011
19
A rare association of long QT syndrome and syndactyly: Timothy syndrome (LQT 8). (21915623)
2011
20
Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome. (22120178)
2011
21
Somatic mosaicism contributes to phenotypic variation in Timothy syndrome. (21910241)
2011
22
Restoration of normal L-type Ca2+ channel function during Timothy syndrome by ablation of an anchoring protein. (21700933)
2011
23
Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome. (21307850)
2011
24
Increased coupled gating of L-type Ca2+ channels during hypertension and Timothy syndrome. (20110531)
2010
25
The Timothy syndrome mutation of cardiac CaV1.2 (L-type) channels: multiple altered gating mechanisms and pharmacological restoration of inactivation. (19074970)
2009
26
The Timothy syndrome mutation differentially affects voltage- and calcium-dependent inactivation of CaV1.2 L-type calcium channels. (18250309)
2008
27
Introduction into Ca(v)2.1 of the homologous mutation of Ca(v)1.2 causing the Timothy syndrome questions the role of V421 in the phenotypic definition of P-type Ca(2+) channel. (18536931)
2008
28
Proarrhythmic defects in Timothy syndrome require calmodulin kinase II. (19001023)
2008
29
A life-threatening complication of the arterial tourniquet in Timothy syndrome. (17474959)
2007
30
Cellular basis for the electrocardiographic and arrhythmic manifestations of Timothy syndrome: effects of ranolazine. (17467634)
2007
31
Cyclosporin and Timothy syndrome increase mode 2 gating of CaV1.2 calcium channels through aberrant phosphorylation of S6 helices. (16537462)
2006
32
Verapamil decreases ventricular tachyarrhythmias in a patient with Timothy syndrome (LQT8). (16876748)
2006
33
Timothy Syndrome (20301577)
1993

Variations for Timothy Syndrome

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

64
id Symbol AA change Variation ID SNP ID
1CACNA1Cp.Gly402SerVAR_026741
2CACNA1Cp.Gly406ArgVAR_026742

Clinvar genetic disease variations for Timothy Syndrome:

6
id Gene Name Type Significance SNP ID Assembly Location
1CACNA1CNM_000719.6(CACNA1C): c.1216G> A (p.Gly406Arg)single nucleotide variantPathogenicrs79891110GRCh37Chr 12, 2614110: 2614110
2CACNA1CNM_000719.6(CACNA1C): c.1204G> A (p.Gly402Ser)single nucleotide variantPathogenicrs80315385GRCh37Chr 12, 2614098: 2614098

Expression for genes affiliated with Timothy Syndrome

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Expression patterns in normal tissues for genes affiliated with Timothy Syndrome

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Pathways for genes affiliated with Timothy Syndrome

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Pathways related to Timothy Syndrome according to GeneCards/GeneDecks:

(show all 38)
idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
Development Activation of ERK by Alpha 1 adrenergic receptors60
9.8CACNA1C, CAMK2G
2
Show member pathways
9.8CACNA1C, CAMK2G
3
Show member pathways
9.8CACNA1C, CAMK2G
4
Show member pathways
9.8CAMK2G, CACNA1C
59.7CACNA1H, CACNA1C
69.7CACNA1H, CACNA1C
7
Show member pathways
9.5CACNA1C, CACNB2
89.3CAMK2G, CACNA1C, CACNA1H
9
Show member pathways
9.3CAMK2G, CACNA1C, CACNA1H
10
Show member pathways
9.2CAMK2G, CACNA2D1, SCN4B
119.1KCNE1, CACNB2, CACNA1C
12
Show member pathways
9.1CACNA1H, CACNA1C, CACNB2
13
Show member pathways
9.1CACNA1H, CACNA1C, CACNB2
149.0CACNA2D1, CACNB2, CACNA1C
15
Show member pathways
Arrhythmogenic right ventricular cardiomyopathy37
9.0CACNA1C, CACNB2, CACNA2D1
169.0CACNA1C, CACNB2, CACNA2D1
17
Show member pathways
9.0CAMK2G, CACNB2, CACNA2D1
18
Show member pathways
8.6CACNA1C, CAMK2G, CACNB2, CACNA2D1
19
Show member pathways
8.6CACNA1H, CACNA1C, CACNB2, CACNA2D1
20
Show member pathways
8.6CACNA1H, CACNA1C, CACNB2, CACNA2D1
218.6CACNA1H, CACNA1C, CACNB2, CACNA2D1
22
Show member pathways
8.6CACNA1H, CACNA1C, CACNB2, CACNA2D1
23
Show member pathways
8.6CACNA2D1, CACNB2, CACNA1C, CACNA1H
24
Show member pathways
MAPK signaling pathway37
8.6CACNA2D1, CACNB2, CACNA1C, CACNA1H
25
Show member pathways
8.6CACNA2D1, CACNB2, CACNA1C, CACNA1H
268.3KCNE1, SCN4B, CACNB2, CACNA1C, CACNA1H
27
Show member pathways
8.2SCN4B, CACNA2D1, CACNB2, CACNA1C, CACNA1H
28
Show member pathways
8.2CACNA2D1, CACNB2, CAMK2G, CACNA1C, CACNA1H
29
Show member pathways
Development Ligand independent activation of ESR1 and ESR260
8.2CACNA1H, CACNA1C, CAMK2G, CACNB2, CACNA2D1
30
Show member pathways
8.2CACNA1H, CACNA1C, CAMK2G, CACNB2, CACNA2D1
31
Show member pathways
8.2CACNA2D1, CACNB2, CAMK2G, CACNA1C, CACNA1H
32
Show member pathways
8.2CACNA2D1, CACNB2, CAMK2G, CACNA1C, CACNA1H
33
Show member pathways
8.2CACNA1H, CACNA1C, CAMK2G, CACNB2, CACNA2D1
34
Show member pathways
8.2CACNA2D1, CACNB2, CAMK2G, CACNA1C, CACNA1H
357.9CACNA1C, CAMK2G, CACNB2, CACNA2D1, SCN4B, KCNE1
36
Show member pathways
7.8SCN4B, CACNA2D1, CACNB2, CAMK2G, CACNA1C, CACNA1H
377.7PSMC4, CACNA2D1, CACNB2, CACNA1C, CACNA1H
38
Show member pathways
7.7PSMC4, CACNA2D1, CACNB2, CACNA1C, CACNA1H

Compounds for genes affiliated with Timothy Syndrome

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Compounds related to Timothy Syndrome according to GeneCards/GeneDecks:

(show all 23)
idCompoundScoreTop Affiliating Genes
1(+-)-bay k 8644619.9CACNA1C, CACNA1H
2nnc 55-0396 dihydrochloride619.9CACNA1C, CACNA1H
3ibutilide44 1110.9CACNA2D1, CACNA1C
4mibefradil dihydrochloride619.9CACNA1C, CACNA1H
5omega-conotoxin gvia61 2810.9CACNA1C, CACNA1H
6pregabalin61 44 1111.8CACNA1H, CACNA1C
7zonisamide44 50 1111.7SCN4B, CACNA1H
8tetrodotoxin44 61 2811.7SCN4B, CAMK2G
9nimodipine44 28 1111.6CACNA1C, CACNB2
10verapamil44 28 50 24 1113.5CACNA1C, CACNB2
11nisoldipine28 44 1111.3CACNA1C, CACNB2, CACNA2D1
12nilvadipine44 1110.3CACNA2D1, CACNB2, CACNA1C
13amlodipine44 50 24 1112.3CACNA1C, CACNB2, CACNA2D1
14nicardipine44 28 1111.3CACNA1C, CACNB2, CACNA2D1
15anisomycin44 1110.0CAMK2G, PSMC4
16isradipine44 28 1110.9CACNA1H, CACNA1C, CACNB2, CACNA2D1
17nitrendipine44 50 28 1111.9CACNA2D1, CACNB2, CACNA1C, CACNA1H
18felodipine44 28 1110.9CACNA2D1, CACNB2, CACNA1C, CACNA1H
19potassium44 24 1110.9CAMK2G, PSMC4, KCNE1
20sodium44 249.8CAMK2G, PSMC4, SCN4B, KCNE1
21mibefradil44 28 1110.6CACNA1H, CACNA1C, CACNB2, PSMC4
22nifedipine44 28 50 1111.5CACNA2D1, CACNB2, CAMK2G, CACNA1C, CACNA1H
23calcium44 50 24 1110.6PSMC4, CACNA2D1, CACNB2, CAMK2G, CACNA1C, CACNA1H

GO Terms for genes affiliated with Timothy Syndrome

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Cellular components related to Timothy Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1Z discGO:0300189.7CACNA1C, KCNE1
2sarcolemmaGO:0423839.1CACNA1H, CACNB2
3voltage-gated calcium channel complexGO:0058918.5CACNA1H, CACNA1C, CACNB2, CACNA2D1

Biological processes related to Timothy Syndrome according to GeneCards/GeneDecks:

(show all 9)
idNameGO IDScoreTop Affiliating Genes
1cardiac muscle cell action potential involved in contractionGO:0860029.9SCN4B, KCNE1
2regulation of ventricular cardiac muscle cell membrane repolarizationGO:0603079.9SCN4B, KCNE1
3regulation of heart rate by cardiac conductionGO:0860919.8SCN4B, KCNE1
4insulin secretionGO:0300739.8CAMK2G, CACNA1C
5regulation of calcium ion transportGO:0519249.6CAMK2G, CACNA2D1
6calcium ion transportGO:0068169.6CAMK2G, CACNA2D1
7calcium ion importGO:0705099.5CACNB2, CACNA1H
8axon guidanceGO:0074119.0CACNA1H, CACNA1C, CACNB2
9synaptic transmissionGO:0072688.9CACNA1C, CAMK2G, CACNB2

Molecular functions related to Timothy Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1high voltage-gated calcium channel activityGO:0083319.5CACNA1C, CACNB2
2voltage-gated calcium channel activityGO:0052458.7CACNA1C, CACNB2, CACNA2D1

Products for genes affiliated with Timothy Syndrome

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Sources for Timothy Syndrome

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet