WITKOS
MCID: WTT002
MIFTS: 41

Witteveen-Kolk Syndrome (WITKOS)

Categories: Fetal diseases, Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases
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Aliases & Classifications for Witteveen-Kolk Syndrome

MalaCards integrated aliases for Witteveen-Kolk Syndrome:

Name: Witteveen-Kolk Syndrome 57 58 73 75
Sin3a-Related Intellectual Disability Syndrome Due to a Point Mutation 58 28 5
Witkos 57 58 73
Sin3a-Related Intellectual Disability Syndrome 58 5

Characteristics:


Inheritance:

Witteveen-Kolk Syndrome: Autosomal dominant 58 57
Sin3a-Related Intellectual Disability Syndrome Due to a Point Mutation: Autosomal dominant 58

Prevelance:

<1/1000000 (Worldwide) 58

Age Of Onset:

Antenatal,Neonatal 58

OMIM®:

57 (Updated 24-Oct-2022)
Miscellaneous:
variable phenotype
caused by a de novo heterozygous gene deletion syndrome at chromosome 15q24 (in some patients)


Classifications:

Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis


Summaries for Witteveen-Kolk Syndrome

UniProtKB/Swiss-Prot: 73 An autosomal dominant syndrome characterized by global developmental delay, mild to severe intellectual disability, and facial dysmorphism. Additional features include short stature, microcephaly, joint hypermotility, and small hands and feet with digital abnormalities. Brain imaging shows dilated ventricles, thin corpus callosum and, in some cases, dysgyria or polymicrogyria.

MalaCards based summary: Witteveen-Kolk Syndrome, also known as sin3a-related intellectual disability syndrome due to a point mutation, is related to alacrima, achalasia, and mental retardation syndrome and chromosome 15q24 deletion syndrome. An important gene associated with Witteveen-Kolk Syndrome is SIN3A (SIN3 Transcription Regulator Family Member A), and among its related pathways/superpathways are Assembly of the pre-replicative complex and RNA Polymerase II Transcription Initiation And Promoter Clearance. Affiliated tissues include brain and eye, and related phenotypes are abnormal facial shape and intellectual disability, mild

OMIM®: 57 Witteveen-Kolk syndrome (WITKOS) is an autosomal dominant disorder with characteristic distinctive facial features, microcephaly, short stature, and mildly impaired intellectual development with delayed cognitive and motor development and subtle anomalies on MRI-brain imaging (summary by Balasubramanian et al., 2021). (613406) (Updated 24-Oct-2022)

Orphanet: 58 A rare genetic neurodevelopmental syndrome characterized by mild intellectual disability, developmental delay, dysmorphic facial features, growth- and feeding problems, hypotonia, epilepsy, behavioral problems and a variety of congenital abnormalities.

Wikipedia: 75 Witteveen-Kolk syndrome, also known as WITKOS and 15q24 microdeletion syndrome, is a rare... more...

Related Diseases for Witteveen-Kolk Syndrome

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

(show all 13)
# Related Disease Score Top Affiliating Genes
1 alacrima, achalasia, and mental retardation syndrome 10.5
2 chromosome 15q24 deletion syndrome 10.4
3 attention deficit-hyperactivity disorder 10.2
4 down syndrome 10.2
5 glaucoma 3, primary congenital, a 10.2
6 megalocornea 10.2
7 brittle bone disorder 10.2
8 autism spectrum disorder 10.2
9 anterior segment dysgenesis 10.2
10 mucolipidosis 10.2
11 microcephaly 10.2
12 albinism 10.2
13 acute promyelocytic leukemia 9.5 SIN3B SIN3A

Graphical network of the top 20 diseases related to Witteveen-Kolk Syndrome:



Diseases related to Witteveen-Kolk Syndrome

Symptoms & Phenotypes for Witteveen-Kolk Syndrome

Human phenotypes related to Witteveen-Kolk Syndrome:

58 30 (show top 50) (show all 128)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormal facial shape 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0001999
2 intellectual disability, mild 58 30 Very rare (1%) Very frequent (99-80%)
HP:0001256
3 brain imaging abnormality 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0410263
4 hearing impairment 58 30 Frequent (33%) Frequent (79-30%)
HP:0000365
5 joint hypermobility 58 30 Frequent (33%) Frequent (79-30%)
HP:0001382
6 ventriculomegaly 58 30 Very rare (1%) Frequent (79-30%)
HP:0002119
7 autistic behavior 58 30 Frequent (33%) Frequent (79-30%)
HP:0000729
8 decreased head circumference 58 30 Frequent (33%) Frequent (79-30%)
HP:0040195
9 mild malformation of cortical development 58 30 Frequent (33%) Frequent (79-30%)
HP:0032059
10 delayed skeletal maturation 58 30 Very rare (1%) Occasional (29-5%)
HP:0002750
11 abnormality of the dentition 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000164
12 obsessive-compulsive behavior 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000722
13 fine hair 58 30 Very rare (1%) Occasional (29-5%)
HP:0002213
14 short attention span 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000736
15 fragile nails 58 30 Very rare (1%) Occasional (29-5%)
HP:0001808
16 clinodactyly 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0030084
17 dysplastic corpus callosum 58 30 Very rare (1%) Occasional (29-5%)
HP:0006989
18 seizure 30 Very rare (1%) HP:0001250
19 frontal bossing 30 Very rare (1%) HP:0002007
20 constipation 30 Very rare (1%) HP:0002019
21 sleep apnea 30 Very rare (1%) HP:0010535
22 high palate 30 Very rare (1%) HP:0000218
23 cataract 30 Very rare (1%) HP:0000518
24 global developmental delay 30 Very rare (1%) HP:0001263
25 depressed nasal bridge 30 Very rare (1%) HP:0005280
26 type ii diabetes mellitus 30 Very rare (1%) HP:0005978
27 hypertelorism 30 Very rare (1%) HP:0000316
28 macrotia 30 Very rare (1%) HP:0000400
29 wide nasal bridge 30 Very rare (1%) HP:0000431
30 delayed speech and language development 30 Very rare (1%) HP:0000750
31 short nose 30 Very rare (1%) HP:0003196
32 microcephaly 30 Very rare (1%) HP:0000252
33 smooth philtrum 30 Very rare (1%) HP:0000319
34 sensorineural hearing impairment 30 Very rare (1%) HP:0000407
35 anteverted nares 30 Very rare (1%) HP:0000463
36 short stature 30 Very rare (1%) HP:0004322
37 gastroesophageal reflux 30 Very rare (1%) HP:0002020
38 fatigue 30 Very rare (1%) HP:0012378
39 intellectual disability, severe 30 Very rare (1%) HP:0010864
40 prominent forehead 30 Very rare (1%) HP:0011220
41 strabismus 30 Very rare (1%) HP:0000486
42 autism 30 Very rare (1%) HP:0000717
43 intrauterine growth retardation 30 Very rare (1%) HP:0001511
44 anxiety 30 Very rare (1%) HP:0000739
45 obesity 30 Very rare (1%) HP:0001513
46 epicanthus 30 Very rare (1%) HP:0000286
47 joint laxity 30 Very rare (1%) HP:0001388
48 downslanted palpebral fissures 30 Very rare (1%) HP:0000494
49 narrow mouth 30 Very rare (1%) HP:0000160
50 clinodactyly of the 5th finger 30 Very rare (1%) HP:0004209

Symptoms via clinical synopsis from OMIM®:

57 (Updated 24-Oct-2022)
Skeletal Spine:
scoliosis

Head And Neck Eyes:
hypertelorism
strabismus
downslanting palpebral fissures
epicanthal folds
microphthalmia, mild
more
Head And Neck Face:
smooth philtrum
facial asymmetry
long face
long philtrum
microretrognathia

Neurologic Central Nervous System:
intellectual disability, mild
hypotonia
thin corpus callosum
enlarged ventricles
mental retardation
more
Growth Other:
intrauterine growth retardation
poor postnatal growth

Head And Neck Mouth:
open mouth
small mouth
high arched palate
full lower lip

Skin Nails Hair Hair:
high anterior hairline
thin hair
broad medial eyebrows that taper laterally

Head And Neck Ears:
large ears
cupped ears

Chest Diaphragm:
diaphragmatic hernia (less common)

Muscle Soft Tissue:
loose connective tissue

Head And Neck Nose:
depressed nasal bridge
broad nasal bridge
high nasal bridge
flaring of nasal alae
wide, short nose

Head And Neck Head:
microcephaly
high forehead

Growth Height:
short stature

Genitourinary External Genitalia Male:
cryptorchidism
hypospadias
microphallus

Skeletal:
joint laxity

Skeletal Hands:
brachydactyly
clinodactyly
hypoplastic thumbs
long, slender fingers
digital abnormalities, variable
more
Neurologic Behavioral Psychiatric Manifestations:
hyperactivity
autistic features
aggression
attention deficit

Growth Weight:
low birth weight
obesity (less common)

Skeletal Feet:
abnormal insertion of the toes

Endocrine Features:
growth hormone deficiency (2 patients)
hypogonadotropic hypogonadism (1 patient)

Clinical features from OMIM®:

613406 (Updated 24-Oct-2022)

GenomeRNAi Phenotypes related to Witteveen-Kolk Syndrome according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-1 9.32 SIN3B
2 Increased shRNA abundance (Z-score > 2) GR00366-A-137 9.32 SIN3A
3 Increased shRNA abundance (Z-score > 2) GR00366-A-150 9.32 SIN3A
4 Increased shRNA abundance (Z-score > 2) GR00366-A-156 9.32 SIN3B
5 Increased shRNA abundance (Z-score > 2) GR00366-A-177 9.32 SIN3A
6 Increased shRNA abundance (Z-score > 2) GR00366-A-186 9.32 SIN3B
7 Increased shRNA abundance (Z-score > 2) GR00366-A-207 9.32 SIN3B
8 Increased shRNA abundance (Z-score > 2) GR00366-A-211 9.32 SIN3A
9 Increased shRNA abundance (Z-score > 2) GR00366-A-74 9.32 SIN3A
10 Increased shRNA abundance (Z-score > 2) GR00366-A-9 9.32 SIN3B

Drugs & Therapeutics for Witteveen-Kolk Syndrome

Search Clinical Trials, NIH Clinical Center for Witteveen-Kolk Syndrome

Genetic Tests for Witteveen-Kolk Syndrome

Genetic tests related to Witteveen-Kolk Syndrome:

# Genetic test Affiliating Genes
1 Sin3a-Related Intellectual Disability Syndrome Due to a Point Mutation 28 SIN3A

Anatomical Context for Witteveen-Kolk Syndrome

Organs/tissues related to Witteveen-Kolk Syndrome:

MalaCards : Brain, Eye

Publications for Witteveen-Kolk Syndrome

Articles related to Witteveen-Kolk Syndrome:

(show all 15)
# Title Authors PMID Year
1
Novel SIN3A mutation identified in a Japanese patient with Witteveen-Kolk syndrome. 62 57 5
30267900 2019
2
Haploinsufficiency of MeCP2-interacting transcriptional co-repressor SIN3A causes mild intellectual disability by affecting the development of cortical integrity. 57 5
27399968 2016
3
Comprehensive study of 28 individuals with SIN3A-related disorder underscoring the associated mild cognitive and distinctive facial phenotype. 62 57
33437032 2021
4
Redefined genomic architecture in 15q24 directed by patient deletion/duplication breakpoint mapping. 57
19557438 2009
5
Congenital diaphragmatic hernia is part of the new 15q24 microdeletion syndrome. 57
19233321 2009
6
A 15q24 microduplication, reciprocal to the recently described 15q24 microdeletion, in a boy sharing clinical features with 15q24 microdeletion syndrome patients. 57
18755302 2008
7
Characterization of a recurrent 15q24 microdeletion syndrome. 57
17360722 2007
8
A report of three patients with an interstitial deletion of chromosome 15q24. 57
16007617 2005
9
Two cases of prenatally diagnosed diaphragmatic hernia accompanied by the same undescribed chromosomal deletion (15q24 de novo) 57
9650775 1998
10
Interstitial deletion of chromosome 15: two cases. 57
3198122 1988
11
Exome Sequencing Identifies a Novel SIN3A Variant in a Patient with Witteveen-Kolk Syndrome. 62
36158056 2022
12
Anterior megalophthalmos in sisters with Witteveen-Kolk syndrome. 62
35144002 2022
13
Witteveen-Kolk syndrome: The first patient from Turkey. 62
33142042 2021
14
Behavior and cognitive functioning in Witteveen-Kolk syndrome. 62
32783353 2020
15
Three rare disease diagnoses in one patient through exome sequencing. 62
31427378 2019

Variations for Witteveen-Kolk Syndrome

ClinVar genetic disease variations for Witteveen-Kolk Syndrome:

5 (show all 37)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SIN3A NM_001145358.2(SIN3A):c.2955_2956del (p.Glu985fs) MICROSAT Pathogenic
253073 rs886037847 GRCh37: 15:75682058-75682059
GRCh38: 15:75389717-75389718
2 SIN3A NM_001145358.2(SIN3A):c.803dup (p.Leu269fs) DUP Pathogenic
253070 rs879255618 GRCh37: 15:75704037-75704038
GRCh38: 15:75411696-75411697
3 SIN3A NM_001145358.2(SIN3A):c.3310C>T (p.Arg1104Ter) SNV Pathogenic
253074 rs879255621 GRCh37: 15:75673043-75673043
GRCh38: 15:75380702-75380702
4 SIN3A NM_001145358.2(SIN3A):c.1759del (p.Ser587fs) DEL Pathogenic
253072 rs879255620 GRCh37: 15:75692476-75692476
GRCh38: 15:75400135-75400135
5 SIN3A NM_001145358.2(SIN3A):c.3118_3119del (p.Gln1040fs) MICROSAT Pathogenic
431101 rs1135401768 GRCh37: 15:75676681-75676682
GRCh38: 15:75384340-75384341
6 SIN3A NM_001145358.2(SIN3A):c.1229del (p.Lys410fs) DEL Pathogenic
1031165 rs2073599549 GRCh37: 15:75702265-75702265
GRCh38: 15:75409924-75409924
7 SIN3A NM_001145358.2(SIN3A):c.1015C>T (p.Gln339Ter) SNV Pathogenic
1065454 GRCh37: 15:75702621-75702621
GRCh38: 15:75410280-75410280
8 SIN3A NM_001145358.2(SIN3A):c.2258_2259dup (p.Glu754fs) DUP Pathogenic
1031167 rs2073271481 GRCh37: 15:75687038-75687039
GRCh38: 15:75394697-75394698
9 SIN3A NM_001145358.2(SIN3A):c.2809_2810del (p.Lys937fs) DEL Pathogenic
450723 rs1555443600 GRCh37: 15:75684624-75684625
GRCh38: 15:75392283-75392284
10 SIN3A NM_001145358.2(SIN3A):c.2803C>T (p.Arg935Ter) SNV Pathogenic
1325072 GRCh37: 15:75684631-75684631
GRCh38: 15:75392290-75392290
11 SIN3A NM_001145358.2(SIN3A):c.848dup (p.His283fs) DUP Pathogenic
560386 rs1567368243 GRCh37: 15:75703992-75703993
GRCh38: 15:75411651-75411652
12 SIN3A NM_001145357.1(SIN3A):c.1010_1013del DEL Pathogenic
253071 rs879255619 GRCh37: 15:75702623-75702626
GRCh38: 15:75410282-75410285
13 SIN3A NM_001145358.2(SIN3A):c.349C>T (p.Gln117Ter) SNV Pathogenic
1700222 GRCh37: 15:75715005-75715005
GRCh38: 15:75422664-75422664
14 SIN3A NM_001145358.2(SIN3A):c.1261dup (p.Ser421fs) DUP Likely Pathogenic
1683675 GRCh37: 15:75702232-75702233
GRCh38: 15:75409891-75409892
15 SIN3A NM_001145358.2(SIN3A):c.3045_3046dup (p.Ile1016fs) MICROSAT Likely Pathogenic
1333264 GRCh37: 15:75676753-75676754
GRCh38: 15:75384412-75384413
16 SIN3A NM_001145358.2(SIN3A):c.3473dup (p.Asn1158fs) DUP Likely Pathogenic
1338870 GRCh37: 15:75668123-75668124
GRCh38: 15:75375782-75375783
17 SIN3A NM_001145358.2(SIN3A):c.2948dup (p.Arg984fs) DUP Likely Pathogenic
1308659 GRCh37: 15:75682065-75682066
GRCh38: 15:75389724-75389725
18 SIN3A NM_001145358.2(SIN3A):c.2005C>T (p.Leu669Phe) SNV Likely Pathogenic
1031166 rs2073302769 GRCh37: 15:75688687-75688687
GRCh38: 15:75396346-75396346
19 SIN3A NM_001145358.2(SIN3A):c.2006T>A (p.Leu669His) SNV Likely Pathogenic
803108 rs1595897117 GRCh37: 15:75688686-75688686
GRCh38: 15:75396345-75396345
20 SIN3A NM_001145358.2(SIN3A):c.866C>A (p.Ser289Ter) SNV Likely Pathogenic
930683 rs1347764887 GRCh37: 15:75703975-75703975
GRCh38: 15:75411634-75411634
21 overlap with 10 genes DUP Uncertain Significance
560141 GRCh37: 15:75600108-76063285
GRCh38:
22 SIN3A NM_001145358.2(SIN3A):c.1477G>C (p.Glu493Gln) SNV Uncertain Significance
1319297 GRCh37: 15:75694242-75694242
GRCh38: 15:75401901-75401901
23 SIN3A NM_001145358.2(SIN3A):c.776A>C (p.His259Pro) SNV Uncertain Significance
1031168 rs1180165033 GRCh37: 15:75704065-75704065
GRCh38: 15:75411724-75411724
24 SIN3A NM_001145358.2(SIN3A):c.1051C>T (p.Pro351Ser) SNV Uncertain Significance
1098647 GRCh37: 15:75702585-75702585
GRCh38: 15:75410244-75410244
25 SIN3A NM_001145358.2(SIN3A):c.212C>T (p.Ser71Phe) SNV Uncertain Significance
1184396 GRCh37: 15:75715142-75715142
GRCh38: 15:75422801-75422801
26 SIN3A NM_001145358.2(SIN3A):c.3640G>A (p.Val1214Ile) SNV Uncertain Significance
1299295 GRCh37: 15:75664502-75664502
GRCh38: 15:75372161-75372161
27 SIN3A NM_001145358.2(SIN3A):c.3346C>T (p.Arg1116Cys) SNV Uncertain Significance
1342453 GRCh37: 15:75673007-75673007
GRCh38: 15:75380666-75380666
28 SIN3A NM_001145358.2(SIN3A):c.2485G>C (p.Gly829Arg) SNV Uncertain Significance
1342510 GRCh37: 15:75684949-75684949
GRCh38: 15:75392608-75392608
29 SIN3A NM_001145358.2(SIN3A):c.3591G>A (p.Gln1197=) SNV Uncertain Significance
1342579 GRCh37: 15:75668006-75668006
GRCh38: 15:75375665-75375665
30 SIN3A NM_001145358.2(SIN3A):c.2063C>T (p.Pro688Leu) SNV Uncertain Significance
1319928 GRCh37: 15:75688629-75688629
GRCh38: 15:75396288-75396288
31 SIN3A NM_001145358.2(SIN3A):c.2842A>G (p.Lys948Glu) SNV Uncertain Significance
1328147 GRCh37: 15:75684592-75684592
GRCh38: 15:75392251-75392251
32 SIN3A NM_001145358.2(SIN3A):c.1373A>G (p.His458Arg) SNV Uncertain Significance
1213737 GRCh37: 15:75699430-75699430
GRCh38: 15:75407089-75407089
33 SIN3A NM_001145358.2(SIN3A):c.3614G>A (p.Arg1205His) SNV Uncertain Significance
1696625 GRCh37: 15:75664528-75664528
GRCh38: 15:75372187-75372187
34 SIN3A NM_001145358.2(SIN3A):c.3359C>G (p.Ala1120Gly) SNV Uncertain Significance
1699067 GRCh37: 15:75672994-75672994
GRCh38: 15:75380653-75380653
35 SIN3A NM_001145358.2(SIN3A):c.286G>A (p.Gly96Ser) SNV Uncertain Significance
1701674 GRCh37: 15:75715068-75715068
GRCh38: 15:75422727-75422727
36 SIN3A NM_001145358.2(SIN3A):c.3592-21T>A SNV Benign
1332968 GRCh37: 15:75664571-75664571
GRCh38: 15:75372230-75372230
37 SIN3A NM_001145358.2(SIN3A):c.3592-20T>A SNV Benign
1274358 GRCh37: 15:75664570-75664570
GRCh38: 15:75372229-75372229

Expression for Witteveen-Kolk Syndrome

Search GEO for disease gene expression data for Witteveen-Kolk Syndrome.

Pathways for Witteveen-Kolk Syndrome

Pathways related to Witteveen-Kolk Syndrome according to GeneCards Suite gene sharing:

(show all 11)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.43 SIN3B SIN3A
2
Show member pathways
12.31 SIN3B SIN3A
3
Show member pathways
12.11 SIN3B SIN3A
4
Show member pathways
11.94 SIN3B SIN3A
5
Show member pathways
11.67 SIN3B SIN3A
6 11.19 SIN3B SIN3A
7 11.1 SIN3B SIN3A
8 11.09 SIN3B SIN3A
9
Show member pathways
10.87 SIN3B SIN3A
10 10.54 SIN3B SIN3A
11 10.17 SIN3B SIN3A

GO Terms for Witteveen-Kolk Syndrome

Cellular components related to Witteveen-Kolk Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 histone deacetylase complex GO:0000118 9.26 SIN3B SIN3A
2 Sin3 complex GO:0016580 8.92 SIN3B SIN3A

Biological processes related to Witteveen-Kolk Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 negative regulation of cell migration GO:0030336 9.26 SIN3B SIN3A
2 histone deacetylation GO:0016575 8.92 SIN3A SIN3B

Molecular functions related to Witteveen-Kolk Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromatin binding GO:0003682 9.26 SIN3B SIN3A
2 transcription corepressor activity GO:0003714 8.92 SIN3A SIN3B

Sources for Witteveen-Kolk Syndrome

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 24-Oct-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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