MCID: WRS002
MIFTS: 43

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 57 12 25 59 75 37 29 13 6 15 40 73
Wabs 57 12 25 59
Wbrs 75

Characteristics:

Orphanet epidemiological data:

59
warsaw breakage syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive


HPO:

32
warsaw breakage syndrome:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Warsaw Breakage Syndrome

Genetics Home Reference : 25 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. 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 wide mouth and high palate

UniProtKB/Swiss-Prot : 75 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.

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.

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 29.9 DDX11 NIPBL
2 fanconi anemia, complementation group a 28.4 BRCA1 BRIP1 DDX11 ERCC1 FANCM
3 xfe progeroid syndrome 9.9 ERCC1 WRN
4 baller-gerold syndrome 9.3 BRIP1 DDX11 ERCC1 TWNK WRN

Symptoms & Phenotypes for Warsaw Breakage Syndrome

Symptoms via clinical synopsis from OMIM:

57
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:

32 (show all 19)
# Description HPO Frequency HPO Source Accession
1 wide mouth 32 HP:0000154
2 high palate 32 HP:0000218
3 microcephaly 32 HP:0000252
4 small face 32 HP:0000274
5 epicanthus 32 HP:0000286
6 sloping forehead 32 HP:0000340
7 hearing impairment 32 HP:0000365
8 cupped ear 32 HP:0000378
9 optic nerve coloboma 32 HP:0000588
10 single transverse palmar crease 32 HP:0000954
11 cutis marmorata 32 HP:0000965
12 intellectual disability 32 HP:0001249
13 global developmental delay 32 HP:0001263
14 generalized hypotonia 32 HP:0001290
15 intrauterine growth retardation 32 HP:0001511
16 ventricular septal defect 32 HP:0001629
17 tetralogy of fallot 32 occasional (7.5%) HP:0001636
18 2-3 toe syndactyly 32 HP:0004691
19 hypoplasia of the cochlea 32 HP:0008586

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

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased vaccinia virus (VACV) infection GR00249-S 9.93 CDC6 DDX11 ENY2 ERCC1 FANCM FES
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:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 10 BRCA1 BRIP1 DDX11 ERCC1 FANCM MAU2
2 mortality/aging MP:0010768 9.77 DDX11 ERCC1 FANCM FES MAU2 NIPBL
3 embryo MP:0005380 9.76 TWNK UBTF BRCA1 DDX11 ERCC1 MAU2
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 29 DDX11

Anatomical Context for Warsaw Breakage Syndrome

MalaCards organs/tissues related to Warsaw Breakage Syndrome:

41
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
The Warsaw breakage syndrome-related protein DDX11 is required for ribosomal RNA synthesis and embryonic development. ( 26089203 )
2015
4
Warsaw Breakage Syndrome - A further report, emphasising cutaneous findings. ( 25701697 )
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:

75
# 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.2271+2T> C single nucleotide variant Pathogenic rs730880279 GRCh37 Chromosome 12, 31255247: 31255247
3 DDX11 NM_030653.3(DDX11): c.2689_2691delAAG (p.Lys897del) deletion Pathogenic rs730880280 GRCh37 Chromosome 12, 31256663: 31256665
4 DDX11 NM_030653.3(DDX11): c.2689_2691delAAG (p.Lys897del) deletion Pathogenic rs730880280 GRCh38 Chromosome 12, 31103729: 31103731
5 DDX11 NM_030653.3(DDX11): c.788G> A (p.Arg263Gln) single nucleotide variant Pathogenic rs201968272 GRCh37 Chromosome 12, 31242081: 31242081
6 DDX11 NM_030653.3(DDX11): c.788G> A (p.Arg263Gln) single nucleotide variant Pathogenic rs201968272 GRCh38 Chromosome 12, 31089147: 31089147

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 12.13 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 10.99 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 chromosome GO:0005694 9.72 BRCA1 DDX11 MAU2 NIPBL WRN
3 nucleoplasm GO:0005654 9.55 ARHGEF5 BRCA1 BRIP1 CBX1 CDC6 DDX11
4 chromatin GO:0000785 9.54 CBX1 MAU2 NIPBL
5 Scc2-Scc4 cohesin loading complex GO:0090694 9.26 MAU2 NIPBL
6 SMC loading complex GO:0032116 9.16 MAU2 NIPBL

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

(show all 26)
# Name GO ID Score Top Affiliating Genes
1 DNA repair GO:0006281 9.81 BRCA1 BRIP1 DDX11 ERCC1 FANCM POLI
2 regulation of signal transduction by p53 class mediator GO:1901796 9.8 BRCA1 BRIP1 WRN
3 nucleic acid phosphodiester bond hydrolysis GO:0090305 9.8 ERCC1 FANCM WRN
4 DNA recombination GO:0006310 9.8 BRCA1 ERCC1 RTEL1 WRN
5 nucleobase-containing compound metabolic process GO:0006139 9.73 BRIP1 DDX11 RTEL1 WRN
6 DNA duplex unwinding GO:0032508 9.71 BRIP1 DDX11 RTEL1 WRN
7 DNA synthesis involved in DNA repair GO:0000731 9.69 BRCA1 BRIP1 WRN
8 replication fork processing GO:0031297 9.67 DDX11 FANCM RTEL1 WRN
9 double-strand break repair GO:0006302 9.65 BRCA1 BRIP1 ERCC1 NIPBL WRN
10 cellular response to DNA damage stimulus GO:0006974 9.65 BRCA1 BRIP1 DDX11 ERCC1 FANCM NIPBL
11 strand displacement GO:0000732 9.62 BRCA1 BRIP1 RTEL1 WRN
12 multicellular organism aging GO:0010259 9.61 ERCC1 WRN
13 mitotic sister chromatid cohesion GO:0007064 9.61 MAU2 NIPBL
14 cellular response to angiotensin GO:1904385 9.6 BRIP1 CDC6
15 t-circle formation GO:0090656 9.59 ERCC1 WRN
16 DNA replication checkpoint GO:0000076 9.58 CDC6 TIMELESS
17 positive regulation of double-strand break repair GO:2000781 9.58 DDX11 TIMELESS
18 cellular response to hydroxyurea GO:0072711 9.57 DDX11 TIMELESS
19 G-quadruplex DNA unwinding GO:0044806 9.56 DDX11 WRN
20 cellular response to cisplatin GO:0072719 9.55 DDX11 TIMELESS
21 replicative cell aging GO:0001302 9.54 ERCC1 WRN
22 maintenance of mitotic sister chromatid cohesion GO:0034088 9.52 MAU2 NIPBL
23 cellular response to bleomycin GO:1904976 9.48 DDX11 TIMELESS
24 cohesin loading GO:0071921 9.46 MAU2 NIPBL
25 DNA replication GO:0006260 9.28 BRCA1 BRIP1 CDC6 DDX11 POLI RTEL1
26 cell cycle GO:0007049 10.02 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 damaged DNA binding GO:0003684 9.69 BRCA1 ERCC1 POLI
4 iron-sulfur cluster binding GO:0051536 9.67 BRIP1 DDX11 RTEL1
5 helicase activity GO:0004386 9.63 BRIP1 DDX11 FANCM RTEL1 TWNK WRN
6 4 iron, 4 sulfur cluster binding GO:0051539 9.61 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 9.48 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 10.1 BRCA1 BRIP1 DDX11 ERCC1 FANCM POLR1A
15 hydrolase activity GO:0016787 10.09 BRIP1 DDX11 ERCC1 FANCM RTEL1 TWNK
16 ATP binding GO:0005524 10.06 BRIP1 CDC6 DDX11 FANCM FES RTEL1

Sources for Warsaw Breakage Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 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 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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