MCID: TMT001
MIFTS: 48

Timothy Syndrome malady

Genetic diseases, Rare diseases categories

Aliases & Classifications for Timothy Syndrome

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Sources:
45OMIM, 9Disease Ontology, 10diseasecard, 19GeneReviews, 41NIH Rare Diseases, 20GeneTests, 21Genetics Home Reference, 11DISEASES, 47Orphanet, 22GTR, 60UMLS, 34MESH via Orphanet, 26ICD10 via Orphanet, 61UMLS via Orphanet
See all sources

Timothy Syndrome, Aliases & Descriptions:

Name: Timothy Syndrome 45 9 10 19 41 20 21 11 47 22 60
Long Qt Syndrome with Syndactyly 19 41 21
Lqt8 41 21 47
Long Qt Syndrome - Syndactyly 41 47
 
Long Qt Syndrome Type 8 41 47
Long Qt Syndrome 8 19 41
Ts 21


Classifications:

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


Characteristics (Orphanet epidemiological data):

47
timothy syndrome:
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide)


External Ids:

OMIM45 601005
Disease Ontology9 DOID:0060173
Orphanet47 65283
MESH via Orphanet34 C536962
ICD10 via Orphanet26 I45.8
UMLS via Orphanet61 C1832916

Summaries for Timothy Syndrome

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NIH Rare Diseases:41 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 atrial fibrillation, and has symptoms including syndactylyand prolonged qt interval. 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:9 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.

OMIM:45 Timothy syndrome is characterized by multiorgan dysfunction, including lethal arrhythmias, webbing of fingers and toes,... (601005) more...

Wikipedia:63 Timothy syndrome is a rare autosomal dominant disorder characterized by physical malformations, as well... more...

GeneReviews summary for timothy

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:

31
Heart, Skin

Animal Models for Timothy Syndrome or affiliated genes

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MGI Mouse Phenotypes related to Timothy Syndrome:

35
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053858.1KCNE1, CACNA2D1, CACNB2, CACNA1C, CACNA1H
2MP:00036317.0KCNE1, PSMC4, CACNA2D1, CACNB2, CACNA1C, CACNA1H

Publications for Timothy Syndrome

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Articles related to Timothy Syndrome:

(show all 35)
idTitleAuthorsYear
1
Gain-of-function mutations in the calcium channel CACNA1C (Cav1.2) cause non-syndromic long-QT but not Timothy syndrome. (25633834)
2015
2
Expanding the phenotype of Timothy syndrome type 2: an adolescent with ventricular fibrillation but normal development. (25691416)
2015
3
Unusual retrospective prenatal findings in a male newborn with Timothy syndrome type 1. (25882468)
2015
4
Exome sequencing helped the fine diagnosis of two siblings afflicted with atypical Timothy syndrome (TS2). (24773605)
2014
5
Cellular mechanisms of ventricular arrhythmias in a mouse model of Timothy syndrome (long QT syndrome 8). (24215710)
2014
6
Dentition abnormalities in a Timothy syndrome patient with a novel genetic mutation: a case report. (24960393)
2014
7
Alteration in basal and depolarization induced transcriptional network in iPSC derived neurons from Timothy syndrome. (25360157)
2014
8
Novel Timothy syndrome mutation leading to increase in CACNA1C window current. (25260352)
2014
9
Modeling Timothy syndrome with iPS cells. (23299782)
2013
10
Inhibition of late sodium current by mexiletine: a novel pharmotherapeutical approach in timothy syndrome. (23580742)
2013
11
Sudden cardiac arrest during anesthesia in a 30-month-old boy with syndactyly: a case of genetically proven Timothy syndrome. (23678275)
2013
12
Timothy syndrome is associated with activity-dependent dendritic retraction in rodent and human neurons. (23313911)
2013
13
Case scenario: anesthesia-related cardiac arrest in a child with Timothy syndrome. (23011317)
2012
14
Ca(V)1.2 I-II linker structure and Timothy syndrome. (22990809)
2012
15
Ranolazine safely decreases ventricular and atrial fibrillation in Timothy syndrome (LQT8). (20883512)
2012
16
Long QT, syndactyly, joint contractures, stroke and novel CACNA1C mutation: expanding the spectrum of Timothy syndrome. (22106044)
2012
17
L-type Ca2+ channel function during Timothy syndrome. (22999068)
2012
18
A Mouse Model of Timothy Syndrome: a Complex Autistic Disorder Resulting from a Point Mutation in Cav1.2. (24371506)
2012
19
Two mechanistically distinct effects of dihydropyridine nifedipine on CaV1.2 L-type CaA^a8_ channels revealed by Timothy syndrome mutation. (22554770)
2012
20
Mouse model of Timothy syndrome recapitulates triad of autistic traits. (21878566)
2011
21
A rare association of long QT syndrome and syndactyly: Timothy syndrome (LQT 8). (21915623)
2011
22
Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome. (22120178)
2011
23
Somatic mosaicism contributes to phenotypic variation in Timothy syndrome. (21910241)
2011
24
Restoration of normal L-type Ca2+ channel function during Timothy syndrome by ablation of an anchoring protein. (21700933)
2011
25
Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome. (21307850)
2011
26
Increased coupled gating of L-type Ca2+ channels during hypertension and Timothy syndrome. (20110531)
2010
27
The Timothy syndrome mutation of cardiac CaV1.2 (L-type) channels: multiple altered gating mechanisms and pharmacological restoration of inactivation. (19074970)
2009
28
The Timothy syndrome mutation differentially affects voltage- and calcium-dependent inactivation of CaV1.2 L-type calcium channels. (18250309)
2008
29
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
30
Proarrhythmic defects in Timothy syndrome require calmodulin kinase II. (19001023)
2008
31
A life-threatening complication of the arterial tourniquet in Timothy syndrome. (17474959)
2007
32
Cellular basis for the electrocardiographic and arrhythmic manifestations of Timothy syndrome: effects of ranolazine. (17467634)
2007
33
Cyclosporin and Timothy syndrome increase mode 2 gating of CaV1.2 calcium channels through aberrant phosphorylation of S6 helices. (16537462)
2006
34
Verapamil decreases ventricular tachyarrhythmias in a patient with Timothy syndrome (LQT8). (16876748)
2006
35
Timothy Syndrome (20301577)
1993

Variations for Timothy Syndrome

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

62
id Symbol AA change Variation ID SNP ID
1CACNA1Cp.Gly402SerVAR_026741
2CACNA1Cp.Gly406ArgVAR_026742
3CACNA1Cp.Ile1186ThrVAR_072381

Clinvar genetic disease variations for Timothy Syndrome:

6
id Gene Variation 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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Search GEO for disease gene expression data for Timothy Syndrome.

Pathways for genes affiliated with Timothy Syndrome

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

(show all 38)
idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
Development Activation of ERK by Alpha 1 adrenergic receptors58
9.8CACNA1C, CAMK2G
2
Show member pathways
9.8CACNA1C, CAMK2G
3
Show member pathways
9.8CACNA1C, CAMK2G
4
Show member pathways
9.8CAMK2G, CACNA1C
5
Show member pathways
9.5CACNA1C, CACNB2
69.3CAMK2G, CACNA1C, CACNA1H
7
Show member pathways
9.3CAMK2G, CACNA1C, CACNA1H
8
Show member pathways
9.2CAMK2G, CACNA2D1, SCN4B
99.1KCNE1, CACNB2, CACNA1C
10
Show member pathways
9.1CACNA1H, CACNA1C, CACNB2
11
Show member pathways
9.1CACNA1H, CACNA1C, CACNB2
129.0CACNA2D1, CACNB2, CACNA1C
13
Show member pathways
Arrhythmogenic right ventricular cardiomyopathy36
9.0CACNA1C, CACNB2, CACNA2D1
149.0CACNA1C, CACNB2, CACNA2D1
15
Show member pathways
9.0CAMK2G, CACNB2, CACNA2D1
16
Show member pathways
8.6CACNA1C, CAMK2G, CACNB2, CACNA2D1
17
Show member pathways
8.6CACNA1H, CACNA1C, CACNB2, CACNA2D1
18
Show member pathways
8.6CACNA1H, CACNA1C, CACNB2, CACNA2D1
198.6CACNA1H, CACNA1C, CACNB2, CACNA2D1
20
Show member pathways
8.6CACNA1H, CACNA1C, CACNB2, CACNA2D1
21
Show member pathways
8.6CACNA2D1, CACNB2, CACNA1C, CACNA1H
22
Show member pathways
MAPK signaling pathway36
8.6CACNA2D1, CACNB2, CACNA1C, CACNA1H
23
Show member pathways
8.6CACNA2D1, CACNB2, CACNA1C, CACNA1H
248.3KCNE1, SCN4B, CACNB2, CACNA1C, CACNA1H
25
Show member pathways
8.2SCN4B, CACNA2D1, CACNB2, CACNA1C, CACNA1H
26
Show member pathways
8.2CACNA2D1, CACNB2, CAMK2G, CACNA1C, CACNA1H
27
Show member pathways
Development Ligand independent activation of ESR1 and ESR258
8.2CACNA1H, CACNA1C, CAMK2G, CACNB2, CACNA2D1
28
Show member pathways
8.2CACNA1H, CACNA1C, CAMK2G, CACNB2, CACNA2D1
29
Show member pathways
8.2CACNA2D1, CACNB2, CAMK2G, CACNA1C, CACNA1H
30
Show member pathways
8.2CACNA2D1, CACNB2, CAMK2G, CACNA1C, CACNA1H
31
Show member pathways
8.2CACNA1H, CACNA1C, CAMK2G, CACNB2, CACNA2D1
32
Show member pathways
8.2CACNA2D1, CACNB2, CAMK2G, CACNA1C, CACNA1H
337.9CACNA1C, CAMK2G, CACNB2, CACNA2D1, SCN4B, KCNE1
34
Show member pathways
7.8SCN4B, CACNA2D1, CACNB2, CAMK2G, CACNA1C, CACNA1H
357.7PSMC4, CACNA2D1, CACNB2, CACNA1C, CACNA1H
36
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 Suite gene sharing:

(show all 23)
idCompoundScoreTop Affiliating Genes
1(+-)-bay k 8644599.9CACNA1C, CACNA1H
2nnc 55-0396 dihydrochloride599.9CACNA1C, CACNA1H
3ibutilide43 1210.9CACNA2D1, CACNA1C
4mibefradil dihydrochloride599.9CACNA1C, CACNA1H
5omega-conotoxin gvia59 2810.9CACNA1C, CACNA1H
6pregabalin59 43 1211.8CACNA1H, CACNA1C
7zonisamide43 49 1211.7SCN4B, CACNA1H
8tetrodotoxin43 59 2811.7SCN4B, CAMK2G
9nimodipine43 28 1211.6CACNA1C, CACNB2
10verapamil43 28 49 24 1213.5CACNA1C, CACNB2
11nisoldipine28 43 1211.3CACNA1C, CACNB2, CACNA2D1
12nilvadipine43 1210.3CACNA2D1, CACNB2, CACNA1C
13amlodipine43 49 24 1212.3CACNA1C, CACNB2, CACNA2D1
14nicardipine43 28 1211.3CACNA1C, CACNB2, CACNA2D1
15anisomycin43 1210.0CAMK2G, PSMC4
16isradipine43 28 1210.9CACNA1H, CACNA1C, CACNB2, CACNA2D1
17nitrendipine43 49 28 1211.9CACNA2D1, CACNB2, CACNA1C, CACNA1H
18felodipine43 28 1210.9CACNA2D1, CACNB2, CACNA1C, CACNA1H
19potassium43 24 1210.9CAMK2G, PSMC4, KCNE1
20sodium43 249.8CAMK2G, PSMC4, SCN4B, KCNE1
21mibefradil43 28 1210.6CACNA1H, CACNA1C, CACNB2, PSMC4
22nifedipine43 28 49 1211.5CACNA2D1, CACNB2, CAMK2G, CACNA1C, CACNA1H
23calcium43 49 24 1210.6PSMC4, 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 Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1Z discGO:00300189.7CACNA1C, KCNE1
2sarcolemmaGO:00423839.1CACNA1H, CACNB2
3voltage-gated calcium channel complexGO:00058918.5CACNA1H, CACNA1C, CACNB2, CACNA2D1

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

(show all 9)
idNameGO IDScoreTop Affiliating Genes
1cardiac muscle cell action potential involved in contractionGO:00860029.9SCN4B, KCNE1
2regulation of ventricular cardiac muscle cell membrane repolarizationGO:00603079.9SCN4B, KCNE1
3regulation of heart rate by cardiac conductionGO:00860919.8SCN4B, KCNE1
4insulin secretionGO:00300739.8CAMK2G, CACNA1C
5regulation of calcium ion transportGO:00519249.6CAMK2G, CACNA2D1
6calcium ion transportGO:00068169.6CAMK2G, CACNA2D1
7calcium ion importGO:00705099.5CACNB2, CACNA1H
8axon guidanceGO:00074119.0CACNA1H, CACNA1C, CACNB2
9synaptic transmissionGO:00072688.9CACNA1C, CAMK2G, CACNB2

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

idNameGO IDScoreTop Affiliating Genes
1high voltage-gated calcium channel activityGO:00083319.5CACNA1C, CACNB2
2voltage-gated calcium channel activityGO:00052458.7CACNA1C, 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
33MeSH
34MESH via Orphanet
35MGI
38NCIt
39NDF-RT
42NINDS
43Novoseek
45OMIM
46OMIM via Orphanet
50PubMed
51QIAGEN
56SNOMED-CT via Orphanet
60UMLS
61UMLS via Orphanet