TKS
MCID: TKN001
MIFTS: 35

Takenouchi-Kosaki Syndrome (TKS)

Categories: Blood diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Takenouchi-Kosaki Syndrome

MalaCards integrated aliases for Takenouchi-Kosaki Syndrome:

Name: Takenouchi-Kosaki Syndrome 58 60 76 30 6 41
Macrothrombocytopenia and Mental Retardation Syndrome 58 76
Tks 58 76
Macrothrombocytopenia-Lymphedema-Developmental Delay-Facial Dysmorphism-Camptodactyly Syndrome 60

Characteristics:

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
highly variable phenotype
de novo mutation (in most patients)


Classifications:



Summaries for Takenouchi-Kosaki Syndrome

OMIM : 58 Takenouchi-Kosaki syndrome is a highly heterogeneous autosomal dominant complex congenital developmental disorder affecting multiple organ systems. The core phenotype includes delayed psychomotor development with variable intellectual disability, dysmorphic facial features, and cardiac, genitourinary, and hematologic or lymphatic defects, including thrombocytopenia and lymphedema. Additional features may include abnormalities on brain imaging, skeletal anomalies, and recurrent infections. Some patients have a milder disease course reminiscent of Noonan syndrome (see, e.g., NS1, 163950) (summary by Martinelli et al., 2018). (616737)

MalaCards based summary : Takenouchi-Kosaki Syndrome, also known as macrothrombocytopenia and mental retardation syndrome, is related to diabetes and deafness, maternally inherited and myoclonic epilepsy associated with ragged-red fibers. An important gene associated with Takenouchi-Kosaki Syndrome is CDC42 (Cell Division Cycle 42). Affiliated tissues include brain, skin and colon, and related phenotypes are inguinal hernia and ptosis

UniProtKB/Swiss-Prot : 76 Takenouchi-Kosaki syndrome: A syndrome characterized by macrothrombocytopenia, lymphedema, mental retardation, developmental delay, and distinctive facial features.

Related Diseases for Takenouchi-Kosaki Syndrome

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

(show top 50) (show all 71)
# Related Disease Score Top Affiliating Genes
1 diabetes and deafness, maternally inherited 11.1
2 myoclonic epilepsy associated with ragged-red fibers 11.1
3 lymphoma 10.3
4 lung cancer 10.3
5 glioma 10.3
6 prostate cancer 10.2
7 herpes simplex 10.2
8 bladder cancer 10.2
9 prostate cancer, hereditary, 8 10.2
10 prostate cancer, hereditary, 6 10.2
11 glioblastoma 10.2
12 vaccinia 10.2
13 glioma susceptibility 1 10.1
14 ovarian cancer 10.1
15 small cell cancer of the lung 10.1
16 blood group, gerbich system 10.1
17 malignant glioma 10.1
18 glioblastoma multiforme 10.1
19 breast cancer 10.0
20 hepatocellular carcinoma 10.0
21 pancreatic cancer 10.0
22 nasopharyngeal carcinoma 10.0
23 cholangiocarcinoma 10.0
24 intrahepatic cholangiocarcinoma 10.0
25 colorectal cancer 10.0
26 keratitis, hereditary 10.0
27 ovarian cancer 1 10.0
28 infantile liver failure syndrome 1 10.0
29 acute liver failure 10.0
30 japanese encephalitis 10.0
31 epilepsy 10.0
32 adenocarcinoma 10.0
33 aplasia cutis congenita, nonsyndromic 9.8
34 esterase b 9.8
35 glaucoma, primary open angle 9.8
36 renal cell carcinoma, nonpapillary 9.8
37 mesothelioma, malignant 9.8
38 myositis 9.8
39 carney complex, type 1 9.8
40 retinoblastoma 9.8
41 schizophrenia 9.8
42 enterocolitis 9.8
43 osteogenic sarcoma 9.8
44 thymoma, familial 9.8
45 caronte 9.8
46 alzheimer disease 12 9.8
47 gastric cancer 9.8
48 blood group, junior system 9.8
49 human herpesvirus 8 9.8
50 leukemia 9.8

Graphical network of the top 20 diseases related to Takenouchi-Kosaki Syndrome:



Diseases related to Takenouchi-Kosaki Syndrome

Symptoms & Phenotypes for Takenouchi-Kosaki Syndrome

Human phenotypes related to Takenouchi-Kosaki Syndrome:

33 (show top 50) (show all 59)
# Description HPO Frequency HPO Source Accession
1 inguinal hernia 33 occasional (7.5%) HP:0000023
2 ptosis 33 very rare (1%) HP:0000508
3 seizures 33 very rare (1%) HP:0001250
4 ataxia 33 very rare (1%) HP:0001251
5 dental malocclusion 33 very rare (1%) HP:0000689
6 global developmental delay 33 very rare (1%) HP:0001263
7 sensorineural hearing impairment 33 very rare (1%) HP:0000407
8 patent ductus arteriosus 33 very rare (1%) HP:0001643
9 lymphedema 33 very rare (1%) HP:0001004
10 thrombocytopenia 33 very rare (1%) HP:0001873
11 ventriculomegaly 33 very rare (1%) HP:0002119
12 short philtrum 33 very rare (1%) HP:0000322
13 thin upper lip vermilion 33 very rare (1%) HP:0000219
14 midface retrusion 33 very rare (1%) HP:0011800
15 highly arched eyebrow 33 very rare (1%) HP:0002553
16 cerebellar atrophy 33 very rare (1%) HP:0001272
17 camptodactyly 33 very rare (1%) HP:0012385
18 exotropia 33 very rare (1%) HP:0000577
19 eversion of lateral third of lower eyelids 33 very rare (1%) HP:0007655
20 progressive microcephaly 33 very rare (1%) HP:0000253
21 increased mean platelet volume 33 very rare (1%) HP:0011877
22 hypertelorism 33 HP:0000316
23 low-set ears 33 HP:0000369
24 clinodactyly 33 HP:0030084
25 intellectual disability 33 HP:0001249
26 widely spaced teeth 33 HP:0000687
27 behavioral abnormality 33 HP:0000708
28 wide nasal bridge 33 HP:0000431
29 abnormal facial shape 33 HP:0001999
30 smooth philtrum 33 HP:0000319
31 optic atrophy 33 HP:0000648
32 prominent forehead 33 HP:0011220
33 immunodeficiency 33 HP:0002721
34 long philtrum 33 HP:0000343
35 absent speech 33 HP:0001344
36 cryptorchidism 33 HP:0000028
37 nevus 33 HP:0003764
38 cerebral cortical atrophy 33 HP:0002120
39 cerebellar hypoplasia 33 HP:0001321
40 wide mouth 33 HP:0000154
41 hypospadias 33 HP:0000047
42 downslanted palpebral fissures 33 HP:0000494
43 upslanted palpebral fissure 33 HP:0000582
44 downturned corners of mouth 33 HP:0002714
45 bulbous nose 33 HP:0000414
46 recurrent infections 33 HP:0002719
47 synophrys 33 HP:0000664
48 proximal placement of thumb 33 HP:0009623
49 hydronephrosis 33 HP:0000126
50 tapered finger 33 HP:0001182

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Eyes:
hypertelorism
ptosis
optic atrophy
strabismus
synophrys
more
Skeletal Hands:
clinodactyly
camptodactyly
proximally placed thumbs
tapered fingers

Skeletal Spine:
scoliosis

Head And Neck Teeth:
widely spaced teeth
malocclusion

Head And Neck Face:
smooth philtrum
long philtrum
short philtrum
midface hypoplasia
bitemporal narrowing
more
Immunology:
immunodeficiency
recurrent infections

Genitourinary External Genitalia Male:
cryptorchidism
hypospadias

Head And Neck Mouth:
wide mouth
thin upper lip
downturned corners of the mouth

Neurologic Behavioral Psychiatric Manifestations:
autistic features
behavioral disorders
attention-deficit

Growth Other:
poor postnatal growth

Cardiovascular Vascular:
pulmonary stenosis

Skeletal:
contractures

Head And Neck Ears:
low-set ears
hearing impairment
posteriorly rotated ears

Neurologic Central Nervous System:
intellectual disability
cerebellar hypoplasia
enlarged ventricles
cortical atrophy
delayed psychomotor development
more
Muscle Soft Tissue:
inguinal hernia
lymphedema
hypotonia

Head And Neck Nose:
wide nasal bridge
flared nostrils
bulbous nasal tip

Head And Neck Head:
prominent forehead
microcephaly (in some patients)

Cardiovascular Heart:
patent ductus arteriosus
septal defects
cardiac defects

Head And Neck Neck:
webbed neck

Genitourinary Kidneys:
hydronephrosis
unilateral renal agenesis

Skeletal Feet:
overlapping toes

Hematology:
thrombocytopenia (in some patients)
enlarged platelets (in some patients)

Skin Nails Hair Skin:
nevi
pigmentary abnormalities

Chest External Features:
pectus deformities

Clinical features from OMIM:

616737

Drugs & Therapeutics for Takenouchi-Kosaki Syndrome

Search Clinical Trials , NIH Clinical Center for Takenouchi-Kosaki Syndrome

Genetic Tests for Takenouchi-Kosaki Syndrome

Genetic tests related to Takenouchi-Kosaki Syndrome:

# Genetic test Affiliating Genes
1 Takenouchi-Kosaki Syndrome 30 CDC42

Anatomical Context for Takenouchi-Kosaki Syndrome

MalaCards organs/tissues related to Takenouchi-Kosaki Syndrome:

42
Brain, Skin, Colon, Bone Marrow, Nk Cells, Kidney

Publications for Takenouchi-Kosaki Syndrome

Articles related to Takenouchi-Kosaki Syndrome:

(show all 27)
# Title Authors Year
1
Tks adaptor proteins at a glance. ( 29311151 )
2018
2
A hot-spot mutation in CDC42 (p.Tyr64Cys) and novel phenotypes in the third patient with Takenouchi-Kosaki syndrome. ( 29335451 )
2018
3
Functional Dysregulation of CDC42 Causes Diverse Developmental Phenotypes. ( 29394990 )
2018
4
Constitutive interaction between 4-1BB and 4-1BBL on murine LPS-activated bone marrow dendritic cells masks detection of 4-1BBL by TKS-1 but not 19H3 antibody. ( 28789924 )
2017
5
Further evidence of a mutation in CDC42 as a cause of a recognizable syndromic form of thrombocytopenia. ( 26708094 )
2016
6
Correction: A Systematic Comparison of the Anti-Tumoural Activity and Toxicity of the Three Adv-TKs. ( 27054322 )
2016
7
Complete Genome Sequence of a γ-Hexachlorocyclohexane Degrader, Sphingobium sp. Strain TKS, Isolated from a γ-Hexachlorocyclohexane-Degrading Microbial Community. ( 27056231 )
2016
8
The role of Tks adaptor proteins in invadopodia formation, growth and metastasis of melanoma. ( 27802184 )
2016
9
Macrothrombocytopenia and developmental delay with a de novo CDC42 mutation: Yet another locus for thrombocytopenia and developmental delay. ( 26386261 )
2015
10
Novel permissive murine immunocompetent orthotopic colon carcinoma model for comparison of the antitumoral and safety profiles of three Adv-TKs. ( 25740134 )
2015
11
A development of chimeric VEGFR2 TK inhibitor based on two ligand conformers from PDB: 1Y6A complex--medicinal chemistry consequences of a TKs analysis. ( 24368209 )
2014
12
A systematic comparison of the anti-tumoural activity and toxicity of the three Adv-TKs. ( 24722669 )
2014
13
Novel permissive murine immunocompetent orthotopic colon carcinoma model for comparison of the antitumoral and safety profiles of three Adv-TKs. ( 25185643 )
2014
14
Tactile and Kinesthetic Stimulation (TKS) intervention improves outcomes in weanling rat bone in a neonatal stress model. ( 23728102 )
2013
15
Takotsubo syndrome (TKS): a possible mechanism of sudden unexplained death in epilepsy (SUDEP). ( 21996459 )
2012
16
Cell migration and invasion in human disease: the Tks adaptor proteins. ( 22260678 )
2012
17
Tactile/kinesthetic stimulation (TKS) increases tibial speed of sound and urinary osteocalcin (U-MidOC and unOC) in premature infants (29-32weeks PMA). ( 22846674 )
2012
18
Direct interaction between Tks proteins and the N-terminal proline-rich region (PRR) of NoxA1 mediates Nox1-dependent ROS generation. ( 20609497 )
2011
19
Regulation of cancer invasion by reactive oxygen species and Tks family scaffold proteins. ( 19755707 )
2009
20
Role of non-receptor and receptor tyrosine kinases (TKs) in the antitumor action of alpha-difluoromethylornithine (DFMO) in breast cancer cells. ( 18097746 )
2008
21
Commentary on Chung BPM, Wong TKS, Suen ESB & Chung JWY (2005) SARS: caring for patients in Hong Kong. Journal of Clinical Nursing 14, 510-517. ( 17038114 )
2006
22
A model for quantitative assessment of visual field changes in primary open-angle glaucoma with a computerized perimeter DICON TKS 4000. ( 9707812 )
1998
23
Differential intracellular compartmentalization of herpetic thymidine kinases (TKs) in TK gene-transfected tumor cells: molecular characterization of the nuclear localization signal of herpes simplex virus type 1 TK. ( 9811686 )
1998
24
Learning effect in automatic static perimetry with Dicon TKS 4000 computed perimeter. ( 10205990 )
1998
25
Influence of stage of glaucoma, age and examination time on reliability parameters in computed perimetry with Dicon TKS 4000. ( 10658349 )
1998
26
Comparing threshold visual fields between the Dicon TKS 4000 automated perimeter and the Humphrey Field Analyzer. ( 8576536 )
1995
27
Establishment of a new natural killer (NK) cell line, TKS-1, from a patient with aggressive type of large granular lymphocyte (LGL) leukemia. ( 7967745 )
1994

Variations for Takenouchi-Kosaki Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Takenouchi-Kosaki Syndrome:

76
# Symbol AA change Variation ID SNP ID
1 CDC42 p.Tyr64Cys VAR_076337 rs864309721

ClinVar genetic disease variations for Takenouchi-Kosaki Syndrome:

6 (show all 12)
# Gene Variation Type Significance SNP ID Assembly Location
1 CDC42 NM_001039802.1(CDC42): c.196A> G (p.Arg66Gly) single nucleotide variant Pathogenic rs797044870 GRCh37 Chromosome 1, 22412949: 22412949
2 CDC42 NM_001039802.1(CDC42): c.196A> G (p.Arg66Gly) single nucleotide variant Pathogenic rs797044870 GRCh38 Chromosome 1, 22086456: 22086456
3 CDC42 NM_001791.3(CDC42): c.191A> G (p.Tyr64Cys) single nucleotide variant Pathogenic/Likely pathogenic rs864309721 GRCh37 Chromosome 1, 22412944: 22412944
4 CDC42 NM_001791.3(CDC42): c.191A> G (p.Tyr64Cys) single nucleotide variant Pathogenic/Likely pathogenic rs864309721 GRCh38 Chromosome 1, 22086451: 22086451
5 CDC42 NM_001791.3(CDC42): c.62T> C (p.Ile21Thr) single nucleotide variant Likely pathogenic rs1064795845 GRCh38 Chromosome 1, 22078540: 22078540
6 CDC42 NM_001791.3(CDC42): c.62T> C (p.Ile21Thr) single nucleotide variant Likely pathogenic rs1064795845 GRCh37 Chromosome 1, 22405033: 22405033
7 CDC42 NM_001791.3(CDC42): c.242G> T (p.Cys81Phe) single nucleotide variant Likely pathogenic rs1553196100 GRCh37 Chromosome 1, 22412995: 22412995
8 CDC42 NM_001791.3(CDC42): c.242G> T (p.Cys81Phe) single nucleotide variant Likely pathogenic rs1553196100 GRCh38 Chromosome 1, 22086502: 22086502
9 CDC42 NM_001791.3(CDC42): c.247T> C (p.Ser83Pro) single nucleotide variant Pathogenic rs1553196101 GRCh38 Chromosome 1, 22086507: 22086507
10 CDC42 NM_001791.3(CDC42): c.247T> C (p.Ser83Pro) single nucleotide variant Pathogenic rs1553196101 GRCh37 Chromosome 1, 22413000: 22413000
11 CDC42 NM_001791.3(CDC42): c.511G> A (p.Glu171Lys) single nucleotide variant Pathogenic rs1553196539 GRCh38 Chromosome 1, 22091452: 22091452
12 CDC42 NM_001791.3(CDC42): c.511G> A (p.Glu171Lys) single nucleotide variant Pathogenic rs1553196539 GRCh37 Chromosome 1, 22417945: 22417945

Expression for Takenouchi-Kosaki Syndrome

Search GEO for disease gene expression data for Takenouchi-Kosaki Syndrome.

Pathways for Takenouchi-Kosaki Syndrome

GO Terms for Takenouchi-Kosaki Syndrome

Sources for Takenouchi-Kosaki Syndrome

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75 UMLS via Orphanet
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