ZTTKS
MCID: ZTT001
MIFTS: 36

Zttk Syndrome (ZTTKS)

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

Aliases & Classifications for Zttk Syndrome

MalaCards integrated aliases for Zttk Syndrome:

Name: Zttk Syndrome 57 20 58 72 36 29 6
Zhu-Tokita-Takenouchi-Kim Syndrome 57 20 58 72
Brain Malformations-Musculoskeletal Abnormalities-Facial Dysmorphism-Intellectual Disability Syndrome 20 58
Zttk Multiple Congenital Anomalies-Mental Retardation Syndrome 57 72
Zttks 57 72
Syndrome, Zhu-Tokita-Takenouchi-Kim 39

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal dominant

Miscellaneous:
variable features
mutations occur de novo


HPO:

31
zttk syndrome:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis


Summaries for Zttk Syndrome

OMIM® : 57 ZTTK syndrome is a severe multisystem developmental disorder characterized by delayed psychomotor development and intellectual disability. Affected individuals have characteristic dysmorphic facial features, hypotonia, poor feeding, poor overall growth, and eye or visual abnormalities. Most patients also have musculoskeletal abnormalities, and some have congenital defects of the heart and urogenital system. Brain imaging usually shows developmental abnormalities such as gyral changes, cortical and/or cerebellar atrophy, and thin corpus callosum (summary by Kim et al., 2016). (617140) (Updated 05-Apr-2021)

MalaCards based summary : Zttk Syndrome, also known as zhu-tokita-takenouchi-kim syndrome, is related to duodenal atresia and gastroparesis. An important gene associated with Zttk Syndrome is SON (SON DNA And RNA Binding Protein). Affiliated tissues include cortex, brain and eye, and related phenotypes are global developmental delay and intellectual disability, severe

KEGG : 36 ZTTK syndrome is an intellectual disability syndrome characterized by intellectual disability and/or developmental delay, malformations of the cerebral cortex, epilepsy, vision problems, musculoskeletal abnormalities, and congenital malformations. Several studies have reported that deleterious variants in SON gene are associated with this disease.

UniProtKB/Swiss-Prot : 72 ZTTK syndrome: An autosomal dominant syndrome characterized by intellectual disability, developmental delay, malformations of the cerebral cortex, epilepsy, vision problems, musculo-skeletal abnormalities, and congenital malformations.

Wikipedia : 73 ZTTK Syndrome (Zhu-Tokita-Takenouchi-Kim syndrome) is a rare disease caused in humans by a genetic... more...

Related Diseases for Zttk Syndrome

Diseases related to Zttk Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 duodenal atresia 10.4
2 gastroparesis 10.4
3 hypoplastic left heart syndrome 10.4
4 growth hormone deficiency 10.4
5 febrile seizures 10.4
6 alacrima, achalasia, and mental retardation syndrome 10.2
7 hypotonia 10.0

Graphical network of the top 20 diseases related to Zttk Syndrome:



Diseases related to Zttk Syndrome

Symptoms & Phenotypes for Zttk Syndrome

Human phenotypes related to Zttk Syndrome:

58 31 (show top 50) (show all 125)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
2 intellectual disability, severe 58 31 frequent (33%) Frequent (79-30%) HP:0010864
3 intrauterine growth retardation 58 31 frequent (33%) Frequent (79-30%) HP:0001511
4 failure to thrive in infancy 58 31 frequent (33%) Frequent (79-30%) HP:0001531
5 hypoplasia of the corpus callosum 58 31 frequent (33%) Frequent (79-30%) HP:0002079
6 autistic behavior 58 31 frequent (33%) Frequent (79-30%) HP:0000729
7 hypermetropia 58 31 frequent (33%) Frequent (79-30%) HP:0000540
8 proportionate short stature 58 31 frequent (33%) Frequent (79-30%) HP:0003508
9 infantile muscular hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0008947
10 spasticity 58 31 occasional (7.5%) Occasional (29-5%) HP:0001257
11 frontal bossing 58 31 occasional (7.5%) Occasional (29-5%) HP:0002007
12 nystagmus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000639
13 dysphagia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002015
14 developmental regression 58 31 occasional (7.5%) Occasional (29-5%) HP:0002376
15 hearing impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000365
16 depressed nasal bridge 58 31 occasional (7.5%) Occasional (29-5%) HP:0005280
17 wide nasal bridge 58 31 occasional (7.5%) Occasional (29-5%) HP:0000431
18 short nose 58 31 occasional (7.5%) Occasional (29-5%) HP:0003196
19 smooth philtrum 58 31 occasional (7.5%) Occasional (29-5%) HP:0000319
20 optic atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0000648
21 gastroesophageal reflux 58 31 occasional (7.5%) Occasional (29-5%) HP:0002020
22 prominent forehead 58 31 occasional (7.5%) Occasional (29-5%) HP:0011220
23 full cheeks 58 31 occasional (7.5%) Occasional (29-5%) HP:0000293
24 progressive visual loss 58 31 occasional (7.5%) Occasional (29-5%) HP:0000529
25 low-set ears 58 31 occasional (7.5%) Occasional (29-5%) HP:0000369
26 horseshoe kidney 58 31 occasional (7.5%) Occasional (29-5%) HP:0000085
27 epicanthus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000286
28 myopia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000545
29 atrial septal defect 58 31 occasional (7.5%) Occasional (29-5%) HP:0001631
30 slender long bone 58 31 occasional (7.5%) Occasional (29-5%) HP:0003100
31 kyphoscoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002751
32 emphysema 58 31 occasional (7.5%) Occasional (29-5%) HP:0002097
33 transient ischemic attack 58 31 occasional (7.5%) Occasional (29-5%) HP:0002326
34 hypoplasia of the maxilla 58 31 occasional (7.5%) Occasional (29-5%) HP:0000327
35 arachnodactyly 58 31 occasional (7.5%) Occasional (29-5%) HP:0001166
36 downslanted palpebral fissures 58 31 occasional (7.5%) Occasional (29-5%) HP:0000494
37 downturned corners of mouth 58 31 occasional (7.5%) Occasional (29-5%) HP:0002714
38 facial asymmetry 58 31 occasional (7.5%) Occasional (29-5%) HP:0000324
39 hemivertebrae 58 31 occasional (7.5%) Occasional (29-5%) HP:0002937
40 protruding ear 58 31 occasional (7.5%) Occasional (29-5%) HP:0000411
41 deeply set eye 58 31 occasional (7.5%) Occasional (29-5%) HP:0000490
42 short philtrum 58 31 occasional (7.5%) Occasional (29-5%) HP:0000322
43 arnold-chiari malformation 58 31 occasional (7.5%) Occasional (29-5%) HP:0002308
44 rib fusion 58 31 occasional (7.5%) Occasional (29-5%) HP:0000902
45 chronic diarrhea 58 31 occasional (7.5%) Occasional (29-5%) HP:0002028
46 thin vermilion border 58 31 occasional (7.5%) Occasional (29-5%) HP:0000233
47 blue sclerae 58 31 occasional (7.5%) Occasional (29-5%) HP:0000592
48 polymicrogyria 58 31 occasional (7.5%) Occasional (29-5%) HP:0002126
49 respiratory failure 58 31 occasional (7.5%) Occasional (29-5%) HP:0002878
50 bifid uvula 58 31 occasional (7.5%) Occasional (29-5%) HP:0000193

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
intellectual disability
developmental regression
cerebellar hypoplasia
hypotonia
enlarged ventricles
more
Head And Neck Face:
frontal bossing
facial asymmetry
short philtrum
midface retraction

Head And Neck Nose:
depressed nasal bridge
broad nasal bridge

Growth Height:
short stature

Head And Neck Ears:
low-set ears

Skeletal:
joint hypermobility
joint contractures

Abdomen Gastrointestinal:
feeding difficulties
gastrointestinal malformations (in some patients)

Cardiovascular Heart:
congenital heart defects (in some patients)

Chest Ribs Sternum Clavicles And Scapulae:
rib abnormalities

Skeletal Feet:
small feet

Immunology:
decreased immunoglobulin levels (in some patients)

Growth Other:
failure to thrive
poor overall growth

Skeletal Spine:
scoliosis
kyphosis
hemivertebrae

Head And Neck Eyes:
optic atrophy
strabismus
hypermetropia
downslanting palpebral fissures
deep-set eyes
more
Head And Neck Mouth:
cleft palate
thin upper lip
high-arched palate
small mouth

Genitourinary Kidneys:
horseshoe kidney
single kidney
dysplastic kidney

Skeletal Skull:
craniosynostosis

Muscle Soft Tissue:
hypotonia

Head And Neck Teeth:
dental abnormalities

Skeletal Hands:
small hands

Genitourinary:
urogenital malformations (in some patients)

Clinical features from OMIM®:

617140 (Updated 05-Apr-2021)

Drugs & Therapeutics for Zttk Syndrome

Search Clinical Trials , NIH Clinical Center for Zttk Syndrome

Genetic Tests for Zttk Syndrome

Genetic tests related to Zttk Syndrome:

# Genetic test Affiliating Genes
1 Zttk Syndrome 29 SON

Anatomical Context for Zttk Syndrome

MalaCards organs/tissues related to Zttk Syndrome:

40
Cortex, Brain, Eye, Kidney, Heart, Bone, Lung

Publications for Zttk Syndrome

Articles related to Zttk Syndrome:

# Title Authors PMID Year
1
Establishing SON in 21q22.11 as a cause a new syndromic form of intellectual disability: Possible contribution to Braddock-Carey syndrome phenotype. 6 57
27256762 2016
2
De Novo Truncating Variants in SON Cause Intellectual Disability, Congenital Malformations, and Failure to Thrive. 57 6
27545676 2016
3
De Novo Mutations in SON Disrupt RNA Splicing of Genes Essential for Brain Development and Metabolism, Causing an Intellectual-Disability Syndrome. 57 6
27545680 2016
4
Whole-exome sequencing in undiagnosed genetic diseases: interpreting 119 trios. 57 6
25590979 2015
5
A de novo heterozygous variant in the SON gene is associated with Zhu-Tokita-Takenouchi-Kim syndrome. 61
32926520 2020
6
Phenotypic expansion in Zhu-Tokita-Takenouchi-Kim syndrome caused by de novo variants in the SON gene. 61
32705777 2020
7
A novel frameshift variant in SON causes Zhu-Tokita-Takenouchi-Kim Syndrome. 61
32291808 2020
8
Knockdown of Son, a mouse homologue of the ZTTK syndrome gene, causes neuronal migration defects and dendritic spine abnormalities. 61
32448361 2020
9
Skin and nails abnormalities in a patient with ZTTK syndrome and a de novo mutation in SON. 61
32045494 2020
10
Clinical and genetic analysis of ZTTK syndrome caused by SON heterozygous mutation c.394C>T. 61
31557424 2019

Variations for Zttk Syndrome

ClinVar genetic disease variations for Zttk Syndrome:

6 (show top 50) (show all 54)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SON NM_138927.3(SON):c.3556C>T (p.Gln1186Ter) SNV Pathogenic 548026 rs1275312464 GRCh37: 21:34925093-34925093
GRCh38: 21:33552787-33552787
2 SON NM_001291412.2(SON):c.245-4852dup Duplication Pathogenic 252927 rs886039778 GRCh37: 21:34924609-34924610
GRCh38: 21:33552303-33552304
3 SON NM_032195.2(SON):c.6233del (p.Pro2078fs) Deletion Pathogenic 252930 rs886039779 GRCh37: 21:34929533-34929533
GRCh38: 21:33557227-33557227
4 SON NM_138927.3(SON):c.3334C>T (p.Arg1112Ter) SNV Pathogenic 423520 rs1064796472 GRCh37: 21:34924871-34924871
GRCh38: 21:33552565-33552565
5 SON NM_138927.3(SON):c.5753_5756del (p.Val1918fs) Deletion Pathogenic 252929 rs886039773 GRCh37: 21:34927288-34927291
GRCh38: 21:33554982-33554985
6 SON NM_001291412.2(SON):c.244+3236del Deletion Pathogenic 631519 rs778418096 GRCh37: 21:34921914-34921914
GRCh38: 21:33549608-33549608
7 SON NM_001291412.2(SON):c.245-5006dup Duplication Pathogenic 803629 rs1601263223 GRCh37: 21:34924455-34924456
GRCh38: 21:33552149-33552150
8 SON NM_138927.4(SON):c.6920G>A (p.Gly2307Glu) SNV Pathogenic 827763 rs1601299278 GRCh37: 21:34945648-34945648
GRCh38: 21:33573342-33573342
9 SON NM_138927.3(SON):c.286C>T (p.Gln96Ter) SNV Pathogenic 252926 rs886039777 GRCh37: 21:34921823-34921823
GRCh38: 21:33549517-33549517
10 SON NM_032195.2(SON):c.6022C>T (p.Arg2008Ter) SNV Pathogenic 453018 rs1555899560 GRCh37: 21:34927559-34927559
GRCh38: 21:33555253-33555253
11 SON NM_138927.4(SON):c.6321+1G>A SNV Pathogenic 973267 GRCh37: 21:34929623-34929623
GRCh38: 21:33557317-33557317
12 SON NM_138927.4(SON):c.5533delinsACG (p.Ser1845fs) Indel Pathogenic 988008 GRCh37: 21:34927070-34927070
GRCh38: 21:33554764-33554764
13 SON NM_138927.3(SON):c.6002_6003insCC (p.Arg2002fs) Insertion Pathogenic/Likely pathogenic 265775 rs886039775 GRCh37: 21:34927538-34927539
GRCh38: 21:33555232-33555233
14 SON NM_001291412.2(SON):c.245-2376_245-2375del Microsatellite Pathogenic/Likely pathogenic 265774 rs886039774 GRCh37: 21:34927083-34927084
GRCh38: 21:33554777-33554778
15 SON NM_001291412.2(SON):c.245-3285del Deletion Pathogenic/Likely pathogenic 265776 rs886039776 GRCh37: 21:34926177-34926177
GRCh38: 21:33553871-33553871
16 SON NM_138927.3(SON):c.268del (p.Ser90fs) Deletion Likely pathogenic 617867 rs1569050345 GRCh37: 21:34921801-34921801
GRCh38: 21:33549495-33549495
17 SON NM_138927.3(SON):c.4055del (p.Pro1352fs) Deletion Likely pathogenic 617868 rs1569056484 GRCh37: 21:34925589-34925589
GRCh38: 21:33553283-33553283
18 SON NM_138927.3(SON):c.4549dup (p.Glu1517fs) Duplication Likely pathogenic 617869 rs1569057333 GRCh37: 21:34926084-34926085
GRCh38: 21:33553778-33553779
19 SON NM_138927.3(SON):c.1881_1882del (p.Val629fs) Deletion Likely pathogenic 617860 rs1569053308 GRCh37: 21:34923418-34923419
GRCh38: 21:33551112-33551113
20 SON NM_001291412.2(SON):c.245-4073_245-4069del Deletion Likely pathogenic 252928 rs1114167303 GRCh37: 21:34925385-34925389
GRCh38: 21:33553079-33553083
21 SON NM_138927.3(SON):c.4999_5013del (p.Asp1667_Asn1671del) Deletion Likely pathogenic 617861 rs1569058041 GRCh37: 21:34926535-34926549
GRCh38: 21:33554229-33554243
22 SON and overlap with 1 gene(s) NM_138927.4(SON):c.1002_5016del (p.Glu335fs) Deletion Likely pathogenic 617862 GRCh37: 21:34922536-34926550
GRCh38: 21:33550230-33554244
23 SON NM_001291412.2(SON):c.245-3567_245-3566del Microsatellite Likely pathogenic 617863 rs1601268952 GRCh37: 21:34925893-34925894
GRCh38: 21:33553587-33553588
24 SON NM_138927.3(SON):c.6087del (p.Ser2029fs) Deletion Likely pathogenic 617864 rs1569059792 GRCh37: 21:34927624-34927624
GRCh38: 21:33555318-33555318
25 SON NM_138927.3(SON):c.3597_3598dup (p.Pro1200fs) Duplication Likely pathogenic 617865 rs1569055781 GRCh37: 21:34925133-34925134
GRCh38: 21:33552827-33552828
26 SON NM_138927.3(SON):c.4151_4174del (p.Leu1384_Val1391del) Deletion Likely pathogenic 617866 rs769691894 GRCh37: 21:34925681-34925704
GRCh38: 21:33553375-33553398
27 SON NM_001291412.2(SON):c.244+5217del Deletion Likely pathogenic 440941 rs1555898531 GRCh37: 21:34923902-34923902
GRCh38: 21:33551596-33551596
28 SON NM_138927.4(SON):c.1658del (p.Val553fs) Deletion Likely pathogenic 869477 GRCh37: 21:34923195-34923195
GRCh38: 21:33550889-33550889
29 SON NM_138927.4(SON):c.245-485_273delinsGTTG Indel Likely pathogenic 996849 GRCh37: 21:34921297-34921810
GRCh38: 21:33548991-33549504
30 SON NM_138927.4(SON):c.7091T>C (p.Met2364Thr) SNV Uncertain significance 992444 GRCh37: 21:34947959-34947959
GRCh38: 21:33575653-33575653
31 SON NM_138927.4(SON):c.2191A>G (p.Met731Val) SNV Uncertain significance 976349 GRCh37: 21:34923728-34923728
GRCh38: 21:33551422-33551422
32 SON NM_138927.4(SON):c.490G>A (p.Ala164Thr) SNV Uncertain significance 873535 GRCh37: 21:34922027-34922027
GRCh38: 21:33549721-33549721
33 SON NM_138927.4(SON):c.5221G>C (p.Asp1741His) SNV Uncertain significance 930395 GRCh37: 21:34926758-34926758
GRCh38: 21:33554452-33554452
34 SON NM_001291412.2(SON):c.244+4931_244+4933del Microsatellite Uncertain significance 634520 rs1601261295 GRCh37: 21:34923612-34923614
GRCh38: 21:33551306-33551308
35 SON NM_138927.4(SON):c.1091T>C (p.Leu364Pro) SNV Uncertain significance 1028929 GRCh37: 21:34922628-34922628
GRCh38: 21:33550322-33550322
36 SON NM_138927.4(SON):c.1568A>G (p.Glu523Gly) SNV Uncertain significance 1028930 GRCh37: 21:34923105-34923105
GRCh38: 21:33550799-33550799
37 SON NM_138927.4(SON):c.2715G>A (p.Met905Ile) SNV Uncertain significance 1028931 GRCh37: 21:34924252-34924252
GRCh38: 21:33551946-33551946
38 SON NM_138927.4(SON):c.311C>A (p.Pro104His) SNV Uncertain significance 1028932 GRCh37: 21:34921848-34921848
GRCh38: 21:33549542-33549542
39 SON NM_138927.4(SON):c.3136G>A (p.Glu1046Lys) SNV Uncertain significance 1030012 GRCh37: 21:34924673-34924673
GRCh38: 21:33552367-33552367
40 SON NM_032195.2(SON):c.3587C>T (p.Pro1196Leu) SNV Uncertain significance 451038 rs1225874870 GRCh37: 21:34925124-34925124
GRCh38: 21:33552818-33552818
41 SON NM_138927.4(SON):c.4548G>A (p.Glu1516=) SNV Uncertain significance 1030013 GRCh37: 21:34926085-34926085
GRCh38: 21:33553779-33553779
42 SON NM_138927.4(SON):c.4901C>T (p.Thr1634Ile) SNV Uncertain significance 1030014 GRCh37: 21:34926438-34926438
GRCh38: 21:33554132-33554132
43 SON NM_138927.4(SON):c.4972C>T (p.Pro1658Ser) SNV Uncertain significance 1030015 GRCh37: 21:34926509-34926509
GRCh38: 21:33554203-33554203
44 SON NM_138927.4(SON):c.5840G>A (p.Arg1947Lys) SNV Uncertain significance 1030016 GRCh37: 21:34927377-34927377
GRCh38: 21:33555071-33555071
45 SON NM_138927.4(SON):c.5891_5892delinsTT (p.Ser1964Ile) Indel Uncertain significance 1030017 GRCh37: 21:34927428-34927429
GRCh38: 21:33555122-33555123
46 SON NM_138927.4(SON):c.5978G>A (p.Arg1993His) SNV Uncertain significance 1030018 GRCh37: 21:34927515-34927515
GRCh38: 21:33555209-33555209
47 SON NM_138927.4(SON):c.637G>C (p.Glu213Gln) SNV Uncertain significance 1030019 GRCh37: 21:34922174-34922174
GRCh38: 21:33549868-33549868
48 SON NM_138927.4(SON):c.6657+316G>A SNV Uncertain significance 1030020 GRCh37: 21:34932397-34932397
GRCh38: 21:33560091-33560091
49 SON NM_138927.4(SON):c.2449G>T (p.Ala817Ser) SNV Uncertain significance 1032269 GRCh37: 21:34923986-34923986
GRCh38: 21:33551680-33551680
50 SON NM_138927.4(SON):c.3530C>T (p.Pro1177Leu) SNV Uncertain significance 1032270 GRCh37: 21:34925067-34925067
GRCh38: 21:33552761-33552761

Expression for Zttk Syndrome

Search GEO for disease gene expression data for Zttk Syndrome.

Pathways for Zttk Syndrome

GO Terms for Zttk Syndrome

Sources for Zttk Syndrome

3 CDC
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10 dbSNP
11 DGIdb
17 EFO
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19 FMA
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30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
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44 MeSH
45 MESH via Orphanet
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56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
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69 Tocris
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71 UMLS via Orphanet
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