TKS
MCID: TKN001
MIFTS: 35

Takenouchi-Kosaki Syndrome (TKS)

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

Aliases & Classifications for Takenouchi-Kosaki Syndrome

MalaCards integrated aliases for Takenouchi-Kosaki Syndrome:

Name: Takenouchi-Kosaki Syndrome 56 58 73 29 6 39
Macrothrombocytopenia and Mental Retardation Syndrome 56 73
Tks 56 73
Macrothrombocytopenia-Lymphedema-Developmental Delay-Facial Dysmorphism-Camptodactyly Syndrome 58

Characteristics:

OMIM:

56
Inheritance:
autosomal dominant

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


HPO:

31
takenouchi-kosaki syndrome:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis
Rare haematological diseases


Summaries for Takenouchi-Kosaki Syndrome

OMIM : 56 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, lung and t cells, and related phenotypes are inguinal hernia and seizures

UniProtKB/Swiss-Prot : 73 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 153)
# Related Disease Score Top Affiliating Genes
1 diabetes and deafness, maternally inherited 11.3
2 myoclonic epilepsy associated with ragged-red fibers 11.3
3 herpes simplex 10.8
4 hypothyroidism 10.6
5 glioma 10.6
6 glial tumor 10.6
7 glioblastoma multiforme 10.5
8 myelofibrosis 10.5
9 branchiootic syndrome 1 10.5
10 alacrima, achalasia, and mental retardation syndrome 10.5
11 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.5
12 congenital hypothyroidism 10.5
13 sensorineural hearing loss 10.5
14 thrombocytopenia 10.5
15 vaccinia 10.4
16 bladder cancer 10.4
17 chickenpox 10.4
18 lung cancer 10.4
19 graft-versus-host disease 10.4
20 lymphoma 10.4
21 hepatocellular carcinoma 10.3
22 ovarian cancer 10.3
23 malignant glioma 10.3
24 paragangliomas 3 10.3
25 prostate cancer 10.3
26 pancreatic cancer 10.3
27 severe combined immunodeficiency 10.3
28 breast cancer 10.2
29 renal cell carcinoma, nonpapillary 10.2
30 keratitis, hereditary 10.2
31 osteogenic sarcoma 10.2
32 nasopharyngeal carcinoma 10.2
33 squamous cell carcinoma 10.2
34 colorectal cancer 10.1
35 lung cancer susceptibility 3 10.1
36 oral squamous cell carcinoma 10.1
37 gliosarcoma 10.1
38 retinoblastoma 10.1
39 small cell cancer of the lung 10.1
40 triiodothyronine receptor auxiliary protein 10.1
41 suppressor of tumorigenicity 3 10.1
42 human immunodeficiency virus type 1 10.1
43 cholangiocarcinoma 10.1
44 variola major 10.1
45 adenoid cystic carcinoma 10.1
46 adenocarcinoma 10.1
47 astrocytoma 10.1
48 familial retinoblastoma 10.1
49 intrahepatic cholangiocarcinoma 10.1
50 smallpox 10.1

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:

58 31 (show top 50) (show all 83)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 inguinal hernia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000023
2 seizures 58 31 very rare (1%) Occasional (29-5%) HP:0001250
3 ptosis 58 31 very rare (1%) Occasional (29-5%) HP:0000508
4 global developmental delay 58 31 very rare (1%) Occasional (29-5%) HP:0001263
5 dental malocclusion 58 31 very rare (1%) Occasional (29-5%) HP:0000689
6 midface retrusion 58 31 very rare (1%) Occasional (29-5%) HP:0011800
7 short philtrum 58 31 very rare (1%) Occasional (29-5%) HP:0000322
8 highly arched eyebrow 58 31 very rare (1%) Occasional (29-5%) HP:0002553
9 patent ductus arteriosus 58 31 very rare (1%) Occasional (29-5%) HP:0001643
10 lymphedema 58 31 very rare (1%) Occasional (29-5%) HP:0001004
11 thrombocytopenia 58 31 very rare (1%) Frequent (79-30%) HP:0001873
12 ventriculomegaly 58 31 very rare (1%) Frequent (79-30%) HP:0002119
13 thin upper lip vermilion 58 31 very rare (1%) Occasional (29-5%) HP:0000219
14 cerebellar atrophy 58 31 very rare (1%) Occasional (29-5%) HP:0001272
15 camptodactyly 58 31 very rare (1%) Occasional (29-5%) HP:0012385
16 increased mean platelet volume 58 31 very rare (1%) Frequent (79-30%) HP:0011877
17 exotropia 58 31 very rare (1%) Occasional (29-5%) HP:0000577
18 eversion of lateral third of lower eyelids 58 31 very rare (1%) Occasional (29-5%) HP:0007655
19 ataxia 31 very rare (1%) HP:0001251
20 sensorineural hearing impairment 31 very rare (1%) HP:0000407
21 progressive microcephaly 31 very rare (1%) HP:0000253
22 hypertelorism 58 31 Occasional (29-5%) HP:0000316
23 clinodactyly 58 31 Occasional (29-5%) HP:0030084
24 intellectual disability 58 31 Frequent (79-30%) HP:0001249
25 scoliosis 58 31 Frequent (79-30%) HP:0002650
26 widely spaced teeth 58 31 Occasional (29-5%) HP:0000687
27 wide nasal bridge 58 31 Occasional (29-5%) HP:0000431
28 abnormal facial shape 58 31 Very frequent (99-80%) HP:0001999
29 downslanted palpebral fissures 58 31 Occasional (29-5%) HP:0000494
30 smooth philtrum 58 31 Occasional (29-5%) HP:0000319
31 optic atrophy 58 31 Occasional (29-5%) HP:0000648
32 prominent forehead 58 31 Occasional (29-5%) HP:0011220
33 immunodeficiency 58 31 Occasional (29-5%) HP:0002721
34 long philtrum 58 31 Occasional (29-5%) HP:0000343
35 narrow forehead 58 31 Occasional (29-5%) HP:0000341
36 absent speech 58 31 Occasional (29-5%) HP:0001344
37 webbed neck 58 31 Occasional (29-5%) HP:0000465
38 nevus 58 31 Occasional (29-5%) HP:0003764
39 wide mouth 58 31 Occasional (29-5%) HP:0000154
40 hypospadias 58 31 Occasional (29-5%) HP:0000047
41 hydronephrosis 58 31 Occasional (29-5%) HP:0000126
42 upslanted palpebral fissure 58 31 Occasional (29-5%) HP:0000582
43 synophrys 58 31 Occasional (29-5%) HP:0000664
44 downturned corners of mouth 58 31 Occasional (29-5%) HP:0002714
45 overlapping toe 58 31 Occasional (29-5%) HP:0001845
46 bulbous nose 58 31 Occasional (29-5%) HP:0000414
47 recurrent infections 58 31 Frequent (79-30%) HP:0002719
48 hypoplasia of the corpus callosum 58 31 Frequent (79-30%) HP:0002079
49 proximal placement of thumb 58 31 Occasional (29-5%) HP:0009623
50 tapered finger 58 31 Occasional (29-5%) HP:0001182

Symptoms via clinical synopsis from OMIM:

56
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

Genitourinary External Genitalia Male:
cryptorchidism
hypospadias

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

Cardiovascular Heart:
patent ductus arteriosus
septal defects
cardiac defects

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

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 29 CDC42

Anatomical Context for Takenouchi-Kosaki Syndrome

MalaCards organs/tissues related to Takenouchi-Kosaki Syndrome:

40
Brain, Lung, T Cells, Myeloid, Heart, Liver, Thyroid

Publications for Takenouchi-Kosaki Syndrome

Articles related to Takenouchi-Kosaki Syndrome:

# Title Authors PMID Year
1
Functional Dysregulation of CDC42 Causes Diverse Developmental Phenotypes. 56 6
29394990 2018
2
Further evidence of a mutation in CDC42 as a cause of a recognizable syndromic form of thrombocytopenia. 56 6
26708094 2016
3
Macrothrombocytopenia and developmental delay with a de novo CDC42 mutation: Yet another locus for thrombocytopenia and developmental delay. 56 6
26386261 2015
4
Multiple alterations of platelet functions dominated by increased secretion in mice lacking Cdc42 in platelets. 56
20139097 2010
5
De novo heterozygous missense and loss-of-function variants in CDC42BPB are associated with a neurodevelopmental phenotype. 61
32031333 2020
6
Systemic Inflammation and Myelofibrosis in a Patient with Takenouchi-Kosaki Syndrome due to CDC42 Tyr64Cys Mutation. 61
31953712 2020
7
Pathogenetic basis of Takenouchi-Kosaki syndrome: Electron microscopy study using platelets in patients and functional studies in a Caenorhabditis elegans model. 61
30872706 2019
8
A hot-spot mutation in CDC42 (p.Tyr64Cys) and novel phenotypes in the third patient with Takenouchi-Kosaki syndrome. 61
29335451 2018

Variations for Takenouchi-Kosaki Syndrome

ClinVar genetic disease variations for Takenouchi-Kosaki Syndrome:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 CDC42 NM_001791.4(CDC42):c.196A>G (p.Arg66Gly)SNV Pathogenic 208668 rs797044870 1:22412949-22412949 1:22086456-22086456
2 CDC42 NM_001791.4(CDC42):c.511G>A (p.Glu171Lys)SNV Pathogenic 487654 rs1553196539 1:22417945-22417945 1:22091452-22091452
3 CDC42 NM_001791.4(CDC42):c.247T>C (p.Ser83Pro)SNV Pathogenic 487652 rs1553196101 1:22413000-22413000 1:22086507-22086507
4 CDC42 NM_001791.4(CDC42):c.191A>G (p.Tyr64Cys)SNV Pathogenic/Likely pathogenic 218950 rs864309721 1:22412944-22412944 1:22086451-22086451
5 CDC42 NM_001791.4(CDC42):c.62T>C (p.Ile21Thr)SNV Likely pathogenic 422537 rs1064795845 1:22405033-22405033 1:22078540-22078540
6 CDC42 NM_001791.4(CDC42):c.242G>T (p.Cys81Phe)SNV Likely pathogenic 432071 rs1553196100 1:22412995-22412995 1:22086502-22086502
7 CDC42 NM_001791.4(CDC42):c.137T>C (p.Ile46Thr)SNV Likely pathogenic 666573 1:22408246-22408246 1:22081753-22081753

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

73
# Symbol AA change Variation ID SNP ID
1 CDC42 p.Tyr64Cys VAR_076337 rs864309721

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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68 SNOMED-CT via HPO
69 TGDB
70 Tocris
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72 UMLS via Orphanet
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