MCID: WRS002
MIFTS: 44

Warsaw Breakage Syndrome

Categories: Genetic diseases, Fetal diseases, Rare diseases

Aliases & Classifications for Warsaw Breakage Syndrome

MalaCards integrated aliases for Warsaw Breakage Syndrome:

Name: Warsaw Breakage Syndrome 53 12 24 55 71 36 28 13 14 69
Wabs 53 12 24 55
Wbrs 71

Characteristics:

Orphanet epidemiological data:

55
warsaw breakage syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

53
Inheritance:
autosomal recessive


HPO:

31
warsaw breakage syndrome:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Warsaw Breakage Syndrome

Genetics Home Reference : 24 Warsaw breakage syndrome is a condition that can cause multiple abnormalities. People with Warsaw breakage syndrome have intellectual disability that varies from mild to severe. They also have impaired growth from birth leading to short stature and a small head size (microcephaly). Affected individuals have distinctive facial features that may include a small forehead, a short nose, a small lower jaw, a flat area between the nose and mouth (philtrum), and prominent cheeks. Other common features include hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss) and heart malformations.

MalaCards based summary : Warsaw Breakage Syndrome, also known as wabs, is related to roberts syndrome and fanconi anemia, complementation group a, and has symptoms including high palate, intellectual disability and hearing impairment. An important gene associated with Warsaw Breakage Syndrome is DDX11 (DEAD/H-Box Helicase 11), and among its related pathways/superpathways are DNA Double-Strand Break Repair and Cell Cycle Checkpoints. Affiliated tissues include skin and heart, and related phenotypes are Increased vaccinia virus (VACV) infection and Increased viability with MLN4924 (a NAE inhibitor)

Disease Ontology : 12 A syndrome mainly characterized by severe growth retardation and microcephaly. It is a new form of cohesinopathy showing defects in sister chromatid cohesion and hypersensitivity to chemicals that induce replication stress, thus combining distinct cytogenetic features seen in Roberts syndrome and Fanconi anemia, respectively. It has material basis in homozygous or compound heterozygous mutation in the DDX11 gene on chromosome 12p11.

UniProtKB/Swiss-Prot : 71 Warsaw breakage syndrome: A syndrome characterized by severe microcephaly, pre- and postnatal growth retardation, facial dysmorphism and abnormal skin pigmentation. Additional features include high arched palate, coloboma of the right optic disk, deafness, ventricular septal defect, toes and fingers abnormalities. At cellular level, drug-induced chromosomal breakage, a feature of Fanconi anemia, and sister chromatid cohesion defects, a feature of Roberts syndrome, coexist.

Description from OMIM: 613398

Related Diseases for Warsaw Breakage Syndrome

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

# Related Disease Score Top Affiliating Genes
1 roberts syndrome 30.0 DDX11 NIPBL
2 fanconi anemia, complementation group a 29.1 BRCA1 BRIP1 DDX11 ERCC1 FANCM
3 parkinsonism with spasticity, x-linked 10.0
4 xfe progeroid syndrome 10.0 ERCC1 WRN
5 bloom syndrome 9.8 BRCA1 FANCM WRN
6 baller-gerold syndrome 9.6 BRIP1 DDX11 ERCC1 TWNK WRN

Graphical network of the top 20 diseases related to Warsaw Breakage Syndrome:



Diseases related to Warsaw Breakage Syndrome

Symptoms & Phenotypes for Warsaw Breakage Syndrome

Symptoms via clinical synopsis from OMIM:

53
Head And Neck Head:
microcephaly

Neurologic Central Nervous System:
hypotonia
mental retardation
psychomotor retardation

Cardiovascular Heart:
tetralogy of fallot (rare)
ventricular septal defect (vsd)

Growth Other:
intrauterine growth retardation (iugr)

Skeletal Hands:
single palmar crease
bilateral clinodactyly of the fifth fingers

Skin Nails Hair Skin:
cutis marmorata (in some patients)
hypopigmented patches (in some patients)
hyperpigmented patches (in some patients)

Head And Neck Face:
small face
elongated face
narrow bifrontal diameter
receding forehead

Head And Neck Mouth:
high-arched palate
large mouth

Head And Neck Ears:
cup-shaped ears
deafness, sensorineural
bilateral hypoplastic cochlea

Skeletal Feet:
syndactyly of the second and third toes

Head And Neck Eyes:
bilateral epicanthal folds
coloboma of the right optic disc

Cardiovascular Vascular:
jugular hypoplasia


Clinical features from OMIM:

613398

Human phenotypes related to Warsaw Breakage Syndrome:

31 (show all 19)
# Description HPO Frequency HPO Source Accession
1 high palate 31 HP:0000218
2 intellectual disability 31 HP:0001249
3 hearing impairment 31 HP:0000365
4 global developmental delay 31 HP:0001263
5 microcephaly 31 HP:0000252
6 epicanthus 31 HP:0000286
7 intrauterine growth retardation 31 HP:0001511
8 wide mouth 31 HP:0000154
9 tetralogy of fallot 31 occasional (7.5%) HP:0001636
10 ventricular septal defect 31 HP:0001629
11 hypoplasia of the cochlea 31 HP:0008586
12 optic nerve coloboma 31 HP:0000588
13 sloping forehead 31 HP:0000340
14 cutis marmorata 31 HP:0000965
15 single transverse palmar crease 31 HP:0000954
16 cupped ear 31 HP:0000378
17 generalized hypotonia 31 HP:0001290
18 2-3 toe syndactyly 31 HP:0004691
19 small face 31 HP:0000274

GenomeRNAi Phenotypes related to Warsaw Breakage Syndrome according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased vaccinia virus (VACV) infection GR00249-S 9.93 UBTF WRN ARHGEF5 BRCA1 BRIP1 CBX1
2 Increased viability with MLN4924 (a NAE inhibitor) GR00250-A-3 9.1 BRCA1 BRIP1 ERCC1 FANCM POLI WRN

MGI Mouse Phenotypes related to Warsaw Breakage Syndrome:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 10 DDX11 ERCC1 FANCM MAU2 NIPBL POLI
2 mortality/aging MP:0010768 9.77 BRCA1 CBX1 DDX11 ERCC1 FANCM FES
3 embryo MP:0005380 9.76 BRCA1 DDX11 ERCC1 MAU2 NIPBL RTEL1
4 neoplasm MP:0002006 9.23 BRCA1 BRIP1 ERCC1 FANCM FES POLI

Drugs & Therapeutics for Warsaw Breakage Syndrome

Search Clinical Trials , NIH Clinical Center for Warsaw Breakage Syndrome

Genetic Tests for Warsaw Breakage Syndrome

Genetic tests related to Warsaw Breakage Syndrome:

# Genetic test Affiliating Genes
1 Warsaw Breakage Syndrome 28 DDX11

Anatomical Context for Warsaw Breakage Syndrome

MalaCards organs/tissues related to Warsaw Breakage Syndrome:

38
Skin, Heart

Publications for Warsaw Breakage Syndrome

Articles related to Warsaw Breakage Syndrome:

# Title Authors Year
1
Clinical Report: Warsaw Breakage Syndrome with small radii and fibulae. ( 28960803 )
2017
2
Tim/Timeless, a member of the replication fork protection complex, operates with the Warsaw breakage syndrome DNA helicase DDX11 in the same fork recovery pathway. ( 26503245 )
2015
3
Warsaw Breakage Syndrome - A further report, emphasising cutaneous findings. ( 25701697 )
2015
4
The Warsaw breakage syndrome-related protein DDX11 is required for ribosomal RNA synthesis and embryonic development. ( 26089203 )
2015
5
Molecular functions and cellular roles of the ChlR1 (DDX11) helicase defective in the rare cohesinopathy Warsaw breakage syndrome. ( 24487782 )
2014
6
Identification and biochemical characterization of a novel mutation in DDX11 causing warsaw breakage syndrome. ( 23033317 )
2013
7
Biochemical characterization of Warsaw breakage syndrome helicase. ( 22102414 )
2012
8
Diagnostic Overlap between Fanconi Anemia and the Cohesinopathies: Roberts Syndrome and Warsaw Breakage Syndrome. ( 21490908 )
2010
9
Warsaw breakage syndrome, a cohesinopathy associated with mutations in the XPD helicase family member DDX11/ChlR1. ( 20137776 )
2010

Variations for Warsaw Breakage Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Warsaw Breakage Syndrome:

71
# Symbol AA change Variation ID SNP ID
1 DDX11 p.Arg263Gln VAR_069099 rs201968272

ClinVar genetic disease variations for Warsaw Breakage Syndrome:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 DDX11 NM_030653.3(DDX11): c.2271+2T> C single nucleotide variant Pathogenic rs730880279 GRCh38 Chromosome 12, 31102313: 31102313
2 DDX11 NM_030653.3(DDX11): c.2689_2691delAAG (p.Lys897del) deletion Pathogenic rs730880280 GRCh37 Chromosome 12, 31256663: 31256665
3 DDX11 NM_030653.3(DDX11): c.788G> A (p.Arg263Gln) single nucleotide variant Pathogenic rs201968272 GRCh37 Chromosome 12, 31242081: 31242081

Expression for Warsaw Breakage Syndrome

Search GEO for disease gene expression data for Warsaw Breakage Syndrome.

Pathways for Warsaw Breakage Syndrome

Pathways related to Warsaw Breakage Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.76 BRCA1 BRIP1 ERCC1 FANCM POLI RTEL1
2
Show member pathways
12.33 BRCA1 BRIP1 CDC6 WRN
3 12.12 BRCA1 BRIP1 CDC6 ERCC1 WRN
4
Show member pathways
11.8 BRCA1 BRIP1 RTEL1 WRN
5
Show member pathways
11.65 BRCA1 BRIP1 ERCC1 RTEL1 WRN
6 11 BRCA1 BRIP1 ERCC1 FANCM POLI
7
Show member pathways
10.89 MAU2 NIPBL
8 10.81 BRCA1 WRN
9 10.52 BRIP1 RTEL1
10 10.37 POLR1A UBTF

GO Terms for Warsaw Breakage Syndrome

Cellular components related to Warsaw Breakage Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleus GO:0005634 9.89 ARHGEF5 BRCA1 BRIP1 CBX1 CDC6 DDX11
2 nucleoplasm GO:0005654 9.55 ARHGEF5 BRCA1 BRIP1 CBX1 CDC6 DDX11
3 chromatin GO:0000785 9.5 CBX1 MAU2 NIPBL
4 Scc2-Scc4 cohesin loading complex GO:0090694 9.26 MAU2 NIPBL
5 SMC loading complex GO:0032116 9.16 MAU2 NIPBL

Biological processes related to Warsaw Breakage Syndrome according to GeneCards Suite gene sharing:

(show all 25)
# Name GO ID Score Top Affiliating Genes
1 regulation of signal transduction by p53 class mediator GO:1901796 9.8 BRCA1 BRIP1 WRN
2 DNA recombination GO:0006310 9.8 BRCA1 ERCC1 RTEL1 WRN
3 nucleic acid phosphodiester bond hydrolysis GO:0090305 9.79 ERCC1 FANCM WRN
4 DNA repair GO:0006281 9.76 BRCA1 BRIP1 DDX11 ERCC1 FANCM POLI
5 double-strand break repair GO:0006302 9.73 BRCA1 BRIP1 ERCC1 WRN
6 nucleobase-containing compound metabolic process GO:0006139 9.71 BRIP1 DDX11 RTEL1 WRN
7 DNA synthesis involved in DNA repair GO:0000731 9.69 BRCA1 BRIP1 WRN
8 DNA duplex unwinding GO:0032508 9.67 BRIP1 DDX11 RTEL1 WRN
9 cellular response to DNA damage stimulus GO:0006974 9.65 BRCA1 BRIP1 DDX11 ERCC1 FANCM NIPBL
10 replication fork processing GO:0031297 9.62 DDX11 FANCM RTEL1 WRN
11 multicellular organism aging GO:0010259 9.61 ERCC1 WRN
12 t-circle formation GO:0090656 9.6 ERCC1 WRN
13 mitotic sister chromatid cohesion GO:0007064 9.59 MAU2 NIPBL
14 cellular response to angiotensin GO:1904385 9.58 BRIP1 CDC6
15 positive regulation of double-strand break repair GO:2000781 9.58 DDX11 TIMELESS
16 cellular response to hydroxyurea GO:0072711 9.57 DDX11 TIMELESS
17 G-quadruplex DNA unwinding GO:0044806 9.56 DDX11 WRN
18 strand displacement GO:0000732 9.56 BRCA1 BRIP1 RTEL1 WRN
19 cellular response to cisplatin GO:0072719 9.55 DDX11 TIMELESS
20 replicative cell aging GO:0001302 9.54 ERCC1 WRN
21 maintenance of mitotic sister chromatid cohesion GO:0034088 9.52 MAU2 NIPBL
22 cohesin loading GO:0071921 9.48 MAU2 NIPBL
23 cellular response to bleomycin GO:1904976 9.46 DDX11 TIMELESS
24 DNA replication GO:0006260 9.28 BRCA1 BRIP1 CDC6 DDX11 POLI RTEL1
25 cell cycle GO:0007049 10.01 BRCA1 CDC6 MAU2 NIPBL TIMELESS

Molecular functions related to Warsaw Breakage Syndrome according to GeneCards Suite gene sharing:

(show all 16)
# Name GO ID Score Top Affiliating Genes
1 nuclease activity GO:0004518 9.71 ERCC1 FANCM WRN
2 single-stranded DNA binding GO:0003697 9.7 DDX11 ERCC1 TWNK
3 iron-sulfur cluster binding GO:0051536 9.67 BRIP1 DDX11 RTEL1
4 damaged DNA binding GO:0003684 9.65 BRCA1 ERCC1 POLI
5 helicase activity GO:0004386 9.63 BRIP1 DDX11 FANCM RTEL1 TWNK WRN
6 4 iron, 4 sulfur cluster binding GO:0051539 9.58 BRIP1 DDX11 RTEL1
7 DNA helicase activity GO:0003678 9.56 TWNK WRN
8 ATP-dependent DNA helicase activity GO:0004003 9.56 BRIP1 DDX11 RTEL1 WRN
9 hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides GO:0016818 9.5 BRIP1 DDX11 RTEL1
10 G-quadruplex DNA binding GO:0051880 9.46 DDX11 WRN
11 chromatin binding GO:0003682 9.28 BRIP1 CBX1 DDX11 ENY2 FANCM NIPBL
12 ATP-dependent helicase activity GO:0008026 9.26 BRIP1 DDX11 RTEL1 WRN
13 protein binding GO:0005515 10.32 ARHGEF5 BRCA1 BRIP1 CBX1 CDC6 DDX11
14 DNA binding GO:0003677 10.16 BRCA1 BRIP1 DDX11 ERCC1 FANCM POLR1A
15 hydrolase activity GO:0016787 10.09 BRIP1 DDX11 ERCC1 FANCM RTEL1 TWNK
16 ATP binding GO:0005524 10.03 BRIP1 CDC6 DDX11 FANCM FES RTEL1

Sources for Warsaw Breakage Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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