TKS
MCID: TKN001
MIFTS: 35

Takenouchi-Kosaki Syndrome (TKS)

Categories: Blood diseases, Cardiovascular 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 circulatory system 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, heart and skin, and related phenotypes are abnormal facial shape and brain imaging abnormality

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 10.8
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 bladder cancer 10.4
16 vaccinia 10.4
17 chickenpox 10.4
18 graft-versus-host disease 10.4
19 lung cancer 10.4
20 hepatocellular carcinoma 10.3
21 ovarian cancer 10.3
22 malignant glioma 10.3
23 paragangliomas 3 10.3
24 severe combined immunodeficiency 10.3
25 prostate cancer 10.3
26 pancreatic cancer 10.3
27 lymphoma 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 leukemia, chronic myeloid 10.1
35 lung cancer susceptibility 3 10.1
36 oral squamous cell carcinoma 10.1
37 gliosarcoma 10.1
38 colorectal cancer 10.1
39 retinoblastoma 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 pachyonychia congenita 3 10.1
45 variola major 10.1
46 adenoid cystic carcinoma 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:

58 31 (show top 50) (show all 84)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormal facial shape 58 31 hallmark (90%) Very frequent (99-80%) HP:0001999
2 brain imaging abnormality 58 31 hallmark (90%) Very frequent (99-80%) HP:0410263
3 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
4 scoliosis 58 31 frequent (33%) Frequent (79-30%) HP:0002650
5 postnatal growth retardation 58 31 frequent (33%) Frequent (79-30%) HP:0008897
6 thrombocytopenia 58 31 very rare (1%) Frequent (79-30%) HP:0001873
7 abnormality of the endocrine system 58 31 frequent (33%) Frequent (79-30%) HP:0000818
8 abnormality of the sternum 58 31 frequent (33%) Frequent (79-30%) HP:0000766
9 hypoplasia of the corpus callosum 58 31 frequent (33%) Frequent (79-30%) HP:0002079
10 recurrent infections 58 31 frequent (33%) Frequent (79-30%) HP:0002719
11 abnormal heart morphology 58 31 frequent (33%) Frequent (79-30%) HP:0001627
12 abnormality of the periventricular white matter 58 31 frequent (33%) Frequent (79-30%) HP:0002518
13 increased mean platelet volume 58 31 very rare (1%) Frequent (79-30%) HP:0011877
14 hearing impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000365
15 global developmental delay 58 31 very rare (1%) Occasional (29-5%) HP:0001263
16 inguinal hernia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000023
17 hypertelorism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000316
18 widely spaced teeth 58 31 occasional (7.5%) Occasional (29-5%) HP:0000687
19 dental malocclusion 58 31 very rare (1%) Occasional (29-5%) HP:0000689
20 wide nasal bridge 58 31 occasional (7.5%) Occasional (29-5%) HP:0000431
21 microcephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0000252
22 smooth philtrum 58 31 occasional (7.5%) Occasional (29-5%) HP:0000319
23 optic atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0000648
24 prominent forehead 58 31 occasional (7.5%) Occasional (29-5%) HP:0011220
25 immunodeficiency 58 31 occasional (7.5%) Occasional (29-5%) HP:0002721
26 absent speech 58 31 occasional (7.5%) Occasional (29-5%) HP:0001344
27 lymphedema 58 31 very rare (1%) Occasional (29-5%) HP:0001004
28 webbed neck 58 31 occasional (7.5%) Occasional (29-5%) HP:0000465
29 ptosis 58 31 very rare (1%) Occasional (29-5%) HP:0000508
30 nevus 58 31 occasional (7.5%) Occasional (29-5%) HP:0003764
31 wide mouth 58 31 occasional (7.5%) Occasional (29-5%) HP:0000154
32 downslanted palpebral fissures 58 31 occasional (7.5%) Occasional (29-5%) HP:0000494
33 upslanted palpebral fissure 58 31 occasional (7.5%) Occasional (29-5%) HP:0000582
34 downturned corners of mouth 58 31 occasional (7.5%) Occasional (29-5%) HP:0002714
35 abnormality of the lymphatic system 58 31 occasional (7.5%) Occasional (29-5%) HP:0100763
36 low-set, posteriorly rotated ears 58 31 occasional (7.5%) Occasional (29-5%) HP:0000368
37 patent ductus arteriosus 58 31 very rare (1%) Occasional (29-5%) HP:0001643
38 hydronephrosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000126
39 dandy-walker malformation 58 31 occasional (7.5%) Occasional (29-5%) HP:0001305
40 highly arched eyebrow 58 31 very rare (1%) Occasional (29-5%) HP:0002553
41 thin upper lip vermilion 58 31 very rare (1%) Occasional (29-5%) HP:0000219
42 long philtrum 58 31 occasional (7.5%) Occasional (29-5%) HP:0000343
43 reduced visual acuity 58 31 occasional (7.5%) Occasional (29-5%) HP:0007663
44 hypospadias 58 31 occasional (7.5%) Occasional (29-5%) HP:0000047
45 short philtrum 58 31 very rare (1%) Occasional (29-5%) HP:0000322
46 bulbous nose 58 31 occasional (7.5%) Occasional (29-5%) HP:0000414
47 proximal placement of thumb 58 31 occasional (7.5%) Occasional (29-5%) HP:0009623
48 midface retrusion 58 31 very rare (1%) Occasional (29-5%) HP:0011800
49 tented upper lip vermilion 58 31 occasional (7.5%) Occasional (29-5%) HP:0010804
50 synophrys 58 31 occasional (7.5%) Occasional (29-5%) HP:0000664

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Ears:
hearing impairment
low-set ears
posteriorly rotated ears

Muscle Soft Tissue:
inguinal hernia
lymphedema
hypotonia

Skeletal Spine:
scoliosis

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

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

Genitourinary External Genitalia Male:
cryptorchidism
hypospadias

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

Genitourinary Kidneys:
hydronephrosis
unilateral renal agenesis

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

Growth Other:
poor postnatal growth

Cardiovascular Vascular:
pulmonary stenosis

Skeletal:
contractures

Neurologic Central Nervous System:
intellectual disability
cerebellar hypoplasia
enlarged ventricles
seizures (in some patients)
delayed psychomotor development
more
Head And Neck Eyes:
hypertelorism
optic atrophy
strabismus
ptosis
synophrys
more
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

Head And Neck Neck:
webbed neck

Cardiovascular Heart:
patent ductus arteriosus
septal defects
cardiac defects

Skeletal Hands:
camptodactyly
clinodactyly
proximally placed thumbs
tapered fingers

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, Heart, 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. 6 56
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
Systemic Inflammation and Myelofibrosis in a Patient with Takenouchi-Kosaki Syndrome due to CDC42 Tyr64Cys Mutation. 61
31953712 2020
6
De novo heterozygous missense and loss-of-function variants in CDC42BPB are associated with a neurodevelopmental phenotype. 61
32031333 2020
7
A Novel CDC42 Mutation in an 11-Year Old Child Manifesting as Syndromic Immunodeficiency, Autoinflammation, Hemophagocytic Lymphohistiocytosis, and Malignancy: A Case Report. 61
32231661 2020
8
Pathogenetic basis of Takenouchi-Kosaki syndrome: Electron microscopy study using platelets in patients and functional studies in a Caenorhabditis elegans model. 61
30872706 2019
9
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.247T>C (p.Ser83Pro)SNV Pathogenic 487652 rs1553196101 1:22413000-22413000 1:22086507-22086507
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.196A>G (p.Arg66Gly)SNV Pathogenic 208668 rs797044870 1:22412949-22412949 1:22086456-22086456
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.137T>C (p.Ile46Thr)SNV Likely pathogenic 666573 1:22408246-22408246 1:22081753-22081753
6 CDC42 NM_001791.4(CDC42):c.62T>C (p.Ile21Thr)SNV Likely pathogenic 422537 rs1064795845 1:22405033-22405033 1:22078540-22078540
7 CDC42 NM_001791.4(CDC42):c.242G>T (p.Cys81Phe)SNV Likely pathogenic 432071 rs1553196100 1:22412995-22412995 1:22086502-22086502

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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72 UMLS via Orphanet
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