MCID: WHM001
MIFTS: 52

Whim Syndrome

Categories: Genetic diseases, Rare diseases, Blood diseases, Immune diseases

Aliases & Classifications for Whim Syndrome

MalaCards integrated aliases for Whim Syndrome:

Name: Whim Syndrome 53 12 49 55 71 13 51 41 14 69
Whims 53 12 49 71
Warts, Hypogammaglobulinemia, Infections, and Myelokathexis 12 49 28
Warts-Hypogammaglobulinemia-Infections-Myelokathexis Syndrome 12 55
Warts, Hypogammaglobulinemia, Infections, and Myelokathexis Syndrome 53
Warts, Hypogammaglobulinemia, Infections and Myelokathexis 71
Warts-Infections-Leukopenia-Myelokatexis Syndrome 55
Wilm 55

Characteristics:

Orphanet epidemiological data:

55
whim syndrome
Inheritance: Autosomal dominant,Autosomal recessive,Not applicable; Prevalence: <1/1000000 (Worldwide),<1/1000000 (France); Age of onset: Adolescent,Adult,Childhood; Age of death: adult;

OMIM:

53
Inheritance:
autosomal dominant

Miscellaneous:
onset in infancy or early childhood


HPO:

31
whim syndrome:
Onset and clinical course infantile onset
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 55  
Rare immunological diseases


External Ids:

OMIM 53 193670
Disease Ontology 12 DOID:0060591
ICD10 32 D81.8
MeSH 41 C536697
Orphanet 55 ORPHA51636
MESH via Orphanet 42 C536697
UMLS via Orphanet 70 C0472817
ICD10 via Orphanet 33 D81.8
MedGen 39 C0472817
UMLS 69 C0472817

Summaries for Whim Syndrome

NIH Rare Diseases : 49 WHIM syndrome is an acronym for a rare immunodeficiency disorder with each letter representing a predominant feature of the condition: (W) = warts; (H) = hypogammaglobulinemia; (I) = infections; and (M) = myelokathexis (retention of neutrophils in the bone marrow). Symptoms usually begin in early childhood with recurrent bacterial infections such as respiratory infections and cellulitis. In later childhood, individuals develop widespread warts that often become persistent despite treatments that are normally effective. Warts that involve the genital area may eventually cause cancer. It is caused by mutations in the CXCR4 gene and is inherited in an autosomal dominant manner. Treatment may include medications that replace antibodies (intravenous immunoglobulin) or increase the number of neutrophils; vaccinations; and prophylacticantibiotics to reduce the risk of infections. Last updated: 11/13/2011

MalaCards based summary : Whim Syndrome, also known as whims, is related to macroglobulinemia and wilms tumor 1, and has symptoms including recurrent upper respiratory tract infections, decreased antibody level in blood and neutropenia. An important gene associated with Whim Syndrome is CXCR4 (C-X-C Motif Chemokine Receptor 4), and among its related pathways/superpathways are Signaling by GPCR and CCR5 Pathway in Macrophages. The drugs Lenograstim and Anti-HIV Agents have been mentioned in the context of this disorder. Affiliated tissues include bone, bone marrow and myeloid, and related phenotype is nervous system.

Disease Ontology : 12 An immunodeficiency disease characterized by neutropenia, hypogammaglobulinemia, and extensive human papillomavirus (HPV) infection. It has material basis in heterozygous mutation in the CXCR4 gene on chromosome 2q22.

OMIM : 53 WHIM syndrome is an immunodeficiency disease characterized by neutropenia, hypogammaglobulinemia, and extensive human papillomavirus (HPV) infection. Despite the peripheral neutropenia, bone marrow aspirates from affected individuals contain abundant mature myeloid cells, a condition termed myelokathexis. The susceptibility to HPV is disproportionate compared with other immunodeficiency conditions (summary by Hernandez et al., 2003). (193670)

UniProtKB/Swiss-Prot : 71 WHIM syndrome: Immunodeficiency disease characterized by neutropenia, hypogammaglobulinemia and extensive human papillomavirus (HPV) infection. Despite the peripheral neutropenia, bone marrow aspirates from affected individuals contain abundant mature myeloid cells, a condition termed myelokathexis.

Related Diseases for Whim Syndrome

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

(show top 50) (show all 98)
# Related Disease Score Top Affiliating Genes
1 macroglobulinemia 29.6 CXCL12 CXCR4
2 wilms tumor 1 12.5
3 wilms tumor 5 12.5
4 wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome 12.4
5 wilms tumor 6 12.4
6 hereditary wilms' tumor 12.3
7 cervical wilms' tumor 12.1
8 wilms tumor 4 12.1
9 wilms tumor 2 12.0
10 perlman syndrome 12.0
11 denys-drash syndrome 12.0
12 wilms tumor and radial bilateral aplasia 11.9
13 wilms tumor predisposition 11.9
14 wilms tumor 3 11.9
15 epithelial predominant wilms' tumor 11.9
16 mixed cell type kidney wilms' tumor 11.9
17 blastema predominant kidney wilms' tumor 11.9
18 stromal predominant kidney wilms' tumor 11.9
19 wilms tumor, aniridia, genitourinary anomalies, mental retardation, and obesity syndrome 11.8
20 ovarian wilms' cancer 11.8
21 metachronous kidney wilms' tumor 11.8
22 familial wilms tumor 2 11.8
23 global developmental delay-lung cysts-overgrowth-wilms tumor syndrome 11.8
24 aniridia 1 11.4
25 frasier syndrome 11.3
26 beckwith-wiedemann syndrome 11.3
27 mulibrey nanism 11.3
28 hemihyperplasia, isolated 11.2
29 rhabdoid tumor predisposition syndrome 1 11.1
30 metanephric adenoma 11.1
31 li-fraumeni syndrome 11.1
32 bohring-opitz syndrome 11.1
33 li-fraumeni syndrome 2 11.1
34 mosaic variegated aneuploidy syndrome 1 10.9
35 mosaic variegated aneuploidy syndrome 3 10.9
36 aniridia and absent patella 10.8
37 hyperparathyroidism 2 with jaw tumors 10.8
38 megalencephaly-capillary malformation-polymicrogyria syndrome 10.8
39 mosaic variegated aneuploidy syndrome 2 10.8
40 thauvin-robinet-faivre syndrome 10.8
41 aniridia 2 10.8
42 simpson-golabi-behmel syndrome 10.8
43 rhabdoid cancer 10.8
44 childhood multilocular cystic kidney neoplasm 10.8
45 mosaic variegated aneuploidy syndrome 10.8
46 leukemia 10.5
47 myeloid leukemia 10.3
48 leukemia, acute myeloid 10.3
49 tetralogy of fallot 10.2
50 aids dementia complex 10.1 CXCL12 CXCR4

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



Diseases related to Whim Syndrome

Symptoms & Phenotypes for Whim Syndrome

Symptoms via clinical synopsis from OMIM:

53
Immunology:
hypogammaglobulinemia
chronic human papillomavirus (hpv) infection
recurrent upper respiratory infections

GenitourinaryInternalGenitaliaFemale:
cervical papillomatosis with cervical dysplasia

Hematology:
myelokathexis (retention of neutrophils in the bone marrow)
bone marrow hypercellularity
peripheral neutropenia
hypermature neutrophils have condensed nuclei connected by long, stringy filaments and vacuolated cytoplasm

GenitourinaryExternalGenitaliaFemale:
vulval condylomata acuminata

SkinNailsHairSkin:
verrucae (warts), multiple


Clinical features from OMIM:

193670

Human phenotypes related to Whim Syndrome:

31 (show all 11)
# Description HPO Frequency HPO Source Accession
1 recurrent upper respiratory tract infections 31 HP:0002788
2 decreased antibody level in blood 31 HP:0004313
3 neutropenia 31 HP:0001875
4 abnormality of female internal genitalia 31 HP:0000008
5 recurrent bacterial infections 31 HP:0002718
6 abnormality of female external genitalia 31 HP:0000055
7 bronchiectasis 31 HP:0002110
8 verrucae 31 HP:0200043
9 igg deficiency 31 HP:0004315
10 bone marrow hypercellularity 31 HP:0031020
11 myelokathexis 31 HP:0031160

MGI Mouse Phenotypes related to Whim Syndrome:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 nervous system MP:0003631 9.1 ACKR3 ADRB2 ARRB2 CXCL12 CXCR4 SAG

Drugs & Therapeutics for Whim Syndrome

Drugs for Whim Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 8)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Lenograstim Approved, Investigational Phase 3 135968-09-1
2 Anti-HIV Agents Phase 3,Phase 1
3 Anti-Infective Agents Phase 3,Phase 1
4 Anti-Retroviral Agents Phase 3,Phase 1
5 Antiviral Agents Phase 3,Phase 1
6 JM 3100 Phase 3,Phase 1
7 Adjuvants, Immunologic Phase 3
8 methionine Nutraceutical Phase 3

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Trial of X4P-001 in Patients With WHIM Syndrome Recruiting NCT03005327 Phase 2, Phase 3 X4P-001;Placebo
2 Plerixafor Versus G-CSF in the Treatment of People With WHIM Syndrome Recruiting NCT02231879 Phase 3 Plerixafor;G-CSF
3 AMD 3100 for Treatment of Myelokathexis Completed NCT01058993 Phase 1 AMD3100 or plerixafor
4 A Phase I Study of Mozobil in the Treatment of Patients With WHIMS Recruiting NCT00967785 Phase 1 Mozobil (TM)
5 A Retrospective and Prospective Natural History Study of Patients With WHIM Syndrome Not yet recruiting NCT03087370

Search NIH Clinical Center for Whim Syndrome

Cochrane evidence based reviews: whim syndrome

Genetic Tests for Whim Syndrome

Genetic tests related to Whim Syndrome:

# Genetic test Affiliating Genes
1 Warts, Hypogammaglobulinemia, Infections, and Myelokathexis 28 CXCR4

Anatomical Context for Whim Syndrome

MalaCards organs/tissues related to Whim Syndrome:

38
Bone, Bone Marrow, Myeloid, Neutrophil, B Cells, T Cells

Publications for Whim Syndrome

Articles related to Whim Syndrome:

(show top 50) (show all 52)
# Title Authors Year
1
Mechanisms of Sustained Neutrophilia in Patient WHIM-09, Cured of WHIM Syndrome by Chromothripsis. ( 29177911 )
2018
2
Preference of Genetic Diagnosis of CXCR4 Mutation Compared with Clinical Diagnosis of WHIM Syndrome. ( 28353164 )
2017
3
CXCR4-Specific Nanobodies as Potential Therapeutics for WHIM syndrome. ( 28768817 )
2017
4
WHIM Syndrome With a Novel CXCR4 Variant in a Korean Child. ( 28643496 )
2017
5
Dysplasia of Granulocytes in a Patient with HPV Disease, Recurrent Infections, and B Lymphopenia: A Novel Variant of WHIM Syndrome? ( 28512628 )
2017
6
Pathogenesis, diagnosis and therapeutic strategies in WHIM syndrome immunodeficiency. ( 29057173 )
2017
7
WHIM Syndrome Caused by WaldenstrAPm's Macroglobulinemia-Associated Mutation CXCR4 (L329fs). ( 27059040 )
2016
8
Chromothriptic cure of WHIM syndrome: Implications for bone marrow transplantation. ( 26459672 )
2015
9
Primary cutaneous follicle center lymphoma in a patient with WHIM syndrome. ( 25571909 )
2015
10
Chromothriptic cure of WHIM syndrome. ( 25662009 )
2015
11
A phase 1 clinical trial of long-term, low-dose treatment of WHIM syndrome with the CXCR4 antagonist plerixafor. ( 24523241 )
2014
12
The CXCR4 mutations in WHIM syndrome impair the stability of the T-cell immunologic synapse. ( 23794067 )
2013
13
G protein-coupled receptor kinase-3-deficient mice exhibit WHIM syndrome features and attenuated inflammatory responses. ( 23935208 )
2013
14
Description and outcome of a cohort of 8 patients with WHIM syndrome from the French Severe Chronic Neutropenia Registry. ( 23009155 )
2012
15
Unexpected developments in immune organs in WHIM syndrome. ( 22700690 )
2012
16
WHIM syndrome caused by a single amino acid substitution in the carboxy-tail of chemokine receptor CXCR4. ( 22596258 )
2012
17
The CXCR4 antagonist plerixafor corrects panleukopenia in patients with WHIM syndrome. ( 21890643 )
2011
18
The CXCR4 antagonist plerixafor is a potential therapy for myelokathexis, WHIM syndrome. ( 21835955 )
2011
19
A report of WHIM syndrome (myelokathexis) - clinical features and bone marrow morphology. ( 23049346 )
2011
20
Clinical and genetic features of Warts, Hypogammaglobulinemia, Infections and Myelokathexis (WHIM) syndrome. ( 21506920 )
2011
21
AMD3100 is a potent antagonist at CXCR4(R334X) , a hyperfunctional mutant chemokine receptor and cause of WHIM syndrome. ( 21070597 )
2011
22
Live imaging of neutrophil motility in a zebrafish model of WHIM syndrome. ( 20592249 )
2010
23
Oligoclonality, impaired class switch and B-cell memory responses in WHIM syndrome. ( 20226738 )
2010
24
WHIM syndrome and oral squamous cell carcinoma. ( 19926501 )
2010
25
A pivotal role for CXCL12 signaling in HPV-mediated transformation of keratinocytes: clues to understanding HPV-pathogenesis in WHIM syndrome. ( 21147466 )
2010
26
CXCL12/CXCR4-axis dysfunctions: Markers of the rare immunodeficiency disorder WHIM syndrome. ( 21178277 )
2010
27
Human papillomavirus typing of verrucae in a patient with WHIM syndrome. ( 20713842 )
2010
28
Defect of plasmacytoid dendritic cells in warts, hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome patients. ( 20736454 )
2010
29
Successful umbilical cord blood stem cell transplantation in a child with WHIM syndrome. ( 19878273 )
2010
30
WHIM syndrome: congenital immune deficiency disease. ( 19057201 )
2009
31
A case of WHIM syndrome associated with diabetes and hypothyroidism. ( 19476565 )
2009
32
Impaired recruitment of Grk6 and beta-Arrestin 2 causes delayed internalization and desensitization of a WHIM syndrome-associated CXCR4 mutant receptor. ( 19956569 )
2009
33
Leukocyte analysis from WHIM syndrome patients reveals a pivotal role for GRK3 in CXCR4 signaling. ( 18274673 )
2008
34
Familial occurrence of warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome. ( 19043667 )
2008
35
[The Whim syndrome: a rare cause of diffuse bronchiectasis. Immune defect of CXCR4 and chronic bronchial suppuration]. ( 18535531 )
2008
36
CXCR4 dimerization and beta-arrestin-mediated signaling account for the enhanced chemotaxis to CXCL12 in WHIM syndrome. ( 18436740 )
2008
37
WHIM syndrome myelokathexis reproduced in the NOD/SCID mouse xenotransplant model engrafted with healthy human stem cells transduced with C-terminus-truncated CXCR4. ( 16946301 )
2007
38
Recurrent CXCR4 sequence variation in a girl with WHIM syndrome. ( 17087743 )
2007
39
WHIM syndrome. ( 17803866 )
2007
40
The WHIM syndrome shows a peculiar dysgranulopoiesis: myelokathexis. ( 16487166 )
2006
41
Stromal-derived factor-1 abolishes constitutive apoptosis of WHIM syndrome neutrophils harbouring a truncating CXCR4 mutation. ( 16899028 )
2006
42
WHIM syndrome: a defect in CXCR4 signaling. ( 16091205 )
2005
43
Enhanced function with decreased internalization of carboxy-terminus truncated CXCR4 responsible for WHIM syndrome. ( 15781337 )
2005
44
WHIM syndromes with different genetic anomalies are accounted for by impaired CXCR4 desensitization to CXCL12. ( 15536153 )
2005
45
The role of a mutation of the CXCR4 gene in WHIM syndrome. ( 16154852 )
2005
46
CXCR4 mutations in WHIM syndrome: a misguided immune system? ( 15661033 )
2005
47
Altered leukocyte response to CXCL12 in patients with warts hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome. ( 15026312 )
2004
48
Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency disease. ( 12692554 )
2003
49
WHIM syndrome: a genetic disorder of leukocyte trafficking. ( 14612668 )
2003
50
Epstein-Barr virus-associated T-lymphoproliferative disease with hemophagocytic syndrome, followed by fatal intestinal B lymphoma in a young adult female with WHIM syndrome. Warts, hypogammaglobulinemia, infections, and myelokathexis. ( 12224006 )
2002

Variations for Whim Syndrome

ClinVar genetic disease variations for Whim Syndrome:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 CXCR4 NM_003467.2(CXCR4): c.1000C> T (p.Arg334Ter) single nucleotide variant Pathogenic rs104893624 GRCh37 Chromosome 2, 136872498: 136872498
2 CXCR4 NM_003467.2(CXCR4): c.1016_1017delCT (p.Ser339Cysfs) deletion Pathogenic rs730880320 GRCh37 Chromosome 2, 136872481: 136872482
3 CXCR4 NM_003467.2(CXCR4): c.1027G> T (p.Glu343Ter) single nucleotide variant Pathogenic rs104893625 GRCh37 Chromosome 2, 136872471: 136872471
4 CXCR4 NM_003467.2(CXCR4): c.1013C> G (p.Ser338Ter) single nucleotide variant Pathogenic rs104893626 GRCh37 Chromosome 2, 136872485: 136872485

Expression for Whim Syndrome

Search GEO for disease gene expression data for Whim Syndrome.

Pathways for Whim Syndrome

Pathways related to Whim Syndrome according to GeneCards Suite gene sharing:

(show all 18)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.64 ACKR3 ADRB2 ARRB2 CXCL12 CXCR4 GRK3
2
Show member pathways
12.42 ARRB2 CXCL12 CXCR4 GRK3
3
Show member pathways
12.22 ADRB2 ARRB2 GRK3
4
Show member pathways
12.19 ACKR3 ADRB2 ARRB2
5 12.06 ARRB2 CXCR4 GRK3
6
Show member pathways
12.01 ADRB2 ARRB2 GRK3
7 11.79 ADRB2 CXCR4 GRK3 SAG
8 11.66 ADRB2 ARRB2 GRK3
9 11.54 ARRB2 GRK3
10 11.54 ADRB2 GRK3 SAG
11
Show member pathways
11.4 ACKR3 CXCL12 CXCR4
12 11.38 CXCL12 CXCR4
13 11.24 CXCL12 CXCR4
14 11.19 ARRB2 GRK3
15 11.04 ADRB2 ARRB2
16 10.97 CXCL12 CXCR4
17 10.9 ARRB2 GRK3
18 10.68 ARRB2 CXCL12 CXCR4

GO Terms for Whim Syndrome

Cellular components related to Whim Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 clathrin-coated pit GO:0005905 8.96 ACKR3 ARRB2
2 early endosome GO:0005769 8.8 ACKR3 ADRB2 CXCR4

Biological processes related to Whim Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chemotaxis GO:0006935 9.61 ACKR3 CXCL12 CXCR4
2 chemokine-mediated signaling pathway GO:0070098 9.5 ACKR3 CXCL12 CXCR4
3 cell chemotaxis GO:0060326 9.48 ARRB2 CXCL12
4 positive regulation of protein ubiquitination GO:0031398 9.46 ADRB2 ARRB2
5 G-protein coupled receptor signaling pathway GO:0007186 9.43 ACKR3 ADRB2 ARRB2 CXCL12 CXCR4 GRK3
6 negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage GO:1902230 9.4 ACKR3 CXCL12
7 detection of temperature stimulus involved in sensory perception of pain GO:0050965 9.37 ARRB2 CXCL12
8 receptor internalization GO:0031623 9.33 ACKR3 ARRB2 GRK3
9 desensitization of G-protein coupled receptor protein signaling pathway by arrestin GO:0002032 9.26 ADRB2 ARRB2
10 signal transduction GO:0007165 9.17 ACKR3 ADRB2 ARRB2 CXCL12 CXCR4 GRK3

Molecular functions related to Whim Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 signal transducer activity GO:0004871 9.33 ACKR3 ADRB2 CXCR4
2 coreceptor activity GO:0015026 8.96 ACKR3 CXCR4
3 C-X-C chemokine receptor activity GO:0016494 8.62 ACKR3 CXCR4

Sources for Whim 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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