TKS
MCID: TKN001
MIFTS: 31

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 57 59 74 29 6 40
Macrothrombocytopenia and Mental Retardation Syndrome 57 74
Tks 57 74
Macrothrombocytopenia-Lymphedema-Developmental Delay-Facial Dysmorphism-Camptodactyly Syndrome 59

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

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


HPO:

32
takenouchi-kosaki syndrome:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 57 616737
Orphanet 59 ORPHA487796

Summaries for Takenouchi-Kosaki Syndrome

OMIM : 57 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 : 74 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 lymphoma 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 glioblastoma multiforme 10.5
14 glioblastoma 10.5
15 vaccinia 10.4
16 bladder cancer 10.4
17 chickenpox 10.4
18 graft-versus-host disease 10.4
19 lung cancer 10.3
20 hepatocellular carcinoma 10.3
21 ovarian cancer 10.3
22 prostate cancer 10.3
23 paragangliomas 3 10.3
24 malignant glioma 10.3
25 renal cell carcinoma, nonpapillary 10.2
26 pancreatic cancer 10.2
27 hematopoietic stem cell transplantation 10.2
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 severe combined immunodeficiency 10.2
34 colorectal cancer 10.1
35 small cell cancer of the lung 10.1
36 lung cancer susceptibility 3 10.1
37 oral squamous cell carcinoma 10.1
38 gliosarcoma 10.1
39 retinoblastoma 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 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:

32 (show top 50) (show all 64)
# Description HPO Frequency HPO Source Accession
1 inguinal hernia 32 occasional (7.5%) HP:0000023
2 ptosis 32 very rare (1%) HP:0000508
3 seizures 32 very rare (1%) HP:0001250
4 ataxia 32 very rare (1%) HP:0001251
5 dental malocclusion 32 very rare (1%) HP:0000689
6 global developmental delay 32 very rare (1%) HP:0001263
7 sensorineural hearing impairment 32 very rare (1%) HP:0000407
8 short philtrum 32 very rare (1%) HP:0000322
9 highly arched eyebrow 32 very rare (1%) HP:0002553
10 patent ductus arteriosus 32 very rare (1%) HP:0001643
11 lymphedema 32 very rare (1%) HP:0001004
12 thrombocytopenia 32 very rare (1%) HP:0001873
13 ventriculomegaly 32 very rare (1%) HP:0002119
14 thin upper lip vermilion 32 very rare (1%) HP:0000219
15 midface retrusion 32 very rare (1%) HP:0011800
16 cerebellar atrophy 32 very rare (1%) HP:0001272
17 camptodactyly 32 very rare (1%) HP:0012385
18 increased mean platelet volume 32 very rare (1%) HP:0011877
19 exotropia 32 very rare (1%) HP:0000577
20 eversion of lateral third of lower eyelids 32 very rare (1%) HP:0007655
21 progressive microcephaly 32 very rare (1%) HP:0000253
22 hypertelorism 32 HP:0000316
23 low-set ears 32 HP:0000369
24 clinodactyly 32 HP:0030084
25 intellectual disability 32 HP:0001249
26 scoliosis 32 HP:0002650
27 widely spaced teeth 32 HP:0000687
28 behavioral abnormality 32 HP:0000708
29 wide nasal bridge 32 HP:0000431
30 abnormal facial shape 32 HP:0001999
31 smooth philtrum 32 HP:0000319
32 optic atrophy 32 HP:0000648
33 prominent forehead 32 HP:0011220
34 immunodeficiency 32 HP:0002721
35 long philtrum 32 HP:0000343
36 narrow forehead 32 HP:0000341
37 generalized hypotonia 32 HP:0001290
38 absent speech 32 HP:0001344
39 cryptorchidism 32 HP:0000028
40 webbed neck 32 HP:0000465
41 nevus 32 HP:0003764
42 cerebral cortical atrophy 32 HP:0002120
43 cerebellar hypoplasia 32 HP:0001321
44 wide mouth 32 HP:0000154
45 hypospadias 32 HP:0000047
46 hydronephrosis 32 HP:0000126
47 downslanted palpebral fissures 32 HP:0000494
48 upslanted palpebral fissure 32 HP:0000582
49 downturned corners of mouth 32 HP:0002714
50 bulbous nose 32 HP:0000414

Symptoms via clinical synopsis from OMIM:

57
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 29 CDC42

Anatomical Context for Takenouchi-Kosaki Syndrome

MalaCards organs/tissues related to Takenouchi-Kosaki Syndrome:

41
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. 8 71
29394990 2018
2
Further evidence of a mutation in CDC42 as a cause of a recognizable syndromic form of thrombocytopenia. 8 71
26708094 2016
3
Macrothrombocytopenia and developmental delay with a de novo CDC42 mutation: Yet another locus for thrombocytopenia and developmental delay. 8 71
26386261 2015
4
Multiple alterations of platelet functions dominated by increased secretion in mice lacking Cdc42 in platelets. 8
20139097 2010
5
Pathogenetic basis of Takenouchi-Kosaki syndrome: Electron microscopy study using platelets in patients and functional studies in a Caenorhabditis elegans model. 38
30872706 2019
6
A hot-spot mutation in CDC42 (p.Tyr64Cys) and novel phenotypes in the third patient with Takenouchi-Kosaki syndrome. 38
29335451 2018

Variations for Takenouchi-Kosaki Syndrome

ClinVar genetic disease variations for Takenouchi-Kosaki Syndrome:

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

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

74
# 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 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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