TKS
MCID: TKN001
MIFTS: 33

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 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
Rare skin 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 and skin, and related phenotypes are inguinal hernia and ptosis

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 150)
# 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 10.9
4 hypothyroidism 10.6
5 glioma 10.6
6 glial tumor 10.6
7 glioblastoma multiforme 10.5
8 branchiootic syndrome 1 10.5
9 alacrima, achalasia, and mental retardation syndrome 10.5
10 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.5
11 congenital hypothyroidism 10.5
12 sensorineural hearing loss 10.5
13 thrombocytopenia 10.5
14 vaccinia 10.4
15 bladder cancer 10.4
16 chickenpox 10.4
17 graft-versus-host disease 10.4
18 lung cancer 10.4
19 hepatocellular carcinoma 10.3
20 ovarian cancer 10.3
21 malignant glioma 10.3
22 paragangliomas 3 10.3
23 lymphoma 10.3
24 renal cell carcinoma, nonpapillary 10.3
25 prostate cancer 10.3
26 pancreatic cancer 10.3
27 severe combined immunodeficiency 10.3
28 breast cancer 10.2
29 keratitis, hereditary 10.2
30 osteogenic sarcoma 10.2
31 nasopharyngeal carcinoma 10.2
32 squamous cell carcinoma 10.2
33 colorectal cancer 10.1
34 lung cancer susceptibility 3 10.1
35 oral squamous cell carcinoma 10.1
36 gliosarcoma 10.1
37 retinoblastoma 10.1
38 small cell cancer of the lung 10.1
39 triiodothyronine receptor auxiliary protein 10.1
40 suppressor of tumorigenicity 3 10.1
41 human immunodeficiency virus type 1 10.1
42 gastric cancer 10.1
43 cholangiocarcinoma 10.1
44 variola major 10.1
45 adenoid cystic carcinoma 10.1
46 melanoma 10.1
47 adenocarcinoma 10.1
48 astrocytoma 10.1
49 familial retinoblastoma 10.1
50 intrahepatic cholangiocarcinoma 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:

31 (show top 50) (show all 64)
# Description HPO Frequency HPO Source Accession
1 inguinal hernia 31 occasional (7.5%) HP:0000023
2 ptosis 31 very rare (1%) HP:0000508
3 seizures 31 very rare (1%) HP:0001250
4 ataxia 31 very rare (1%) HP:0001251
5 dental malocclusion 31 very rare (1%) HP:0000689
6 global developmental delay 31 very rare (1%) HP:0001263
7 sensorineural hearing impairment 31 very rare (1%) HP:0000407
8 midface retrusion 31 very rare (1%) HP:0011800
9 short philtrum 31 very rare (1%) HP:0000322
10 highly arched eyebrow 31 very rare (1%) HP:0002553
11 patent ductus arteriosus 31 very rare (1%) HP:0001643
12 lymphedema 31 very rare (1%) HP:0001004
13 thrombocytopenia 31 very rare (1%) HP:0001873
14 ventriculomegaly 31 very rare (1%) HP:0002119
15 thin upper lip vermilion 31 very rare (1%) HP:0000219
16 cerebellar atrophy 31 very rare (1%) HP:0001272
17 camptodactyly 31 very rare (1%) HP:0012385
18 increased mean platelet volume 31 very rare (1%) HP:0011877
19 exotropia 31 very rare (1%) HP:0000577
20 eversion of lateral third of lower eyelids 31 very rare (1%) HP:0007655
21 progressive microcephaly 31 very rare (1%) HP:0000253
22 hypertelorism 31 HP:0000316
23 low-set ears 31 HP:0000369
24 clinodactyly 31 HP:0030084
25 intellectual disability 31 HP:0001249
26 scoliosis 31 HP:0002650
27 widely spaced teeth 31 HP:0000687
28 behavioral abnormality 31 HP:0000708
29 wide nasal bridge 31 HP:0000431
30 abnormal facial shape 31 HP:0001999
31 cryptorchidism 31 HP:0000028
32 downslanted palpebral fissures 31 HP:0000494
33 cerebral cortical atrophy 31 HP:0002120
34 smooth philtrum 31 HP:0000319
35 optic atrophy 31 HP:0000648
36 prominent forehead 31 HP:0011220
37 immunodeficiency 31 HP:0002721
38 long philtrum 31 HP:0000343
39 narrow forehead 31 HP:0000341
40 generalized hypotonia 31 HP:0001290
41 absent speech 31 HP:0001344
42 webbed neck 31 HP:0000465
43 nevus 31 HP:0003764
44 cerebellar hypoplasia 31 HP:0001321
45 wide mouth 31 HP:0000154
46 hypospadias 31 HP:0000047
47 posteriorly rotated ears 31 HP:0000358
48 hydronephrosis 31 HP:0000126
49 upslanted palpebral fissure 31 HP:0000582
50 synophrys 31 HP:0000664

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, Skin

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. 6 56
26386261 2015
4
Multiple alterations of platelet functions dominated by increased secretion in mice lacking Cdc42 in platelets. 56
20139097 2010
5
Pathogenetic basis of Takenouchi-Kosaki syndrome: Electron microscopy study using platelets in patients and functional studies in a Caenorhabditis elegans model. 61
30872706 2019
6
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.247T>C (p.Ser83Pro)SNV Pathogenic 487652 rs1553196101 1:22413000-22413000 1:22086507-22086507
3 CDC42 NM_001791.4(CDC42):c.511G>A (p.Glu171Lys)SNV Pathogenic 487654 rs1553196539 1:22417945-22417945 1:22091452-22091452
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 NC_000001.11:g.22081753T>Cundetermined variant Likely pathogenic 666573

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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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