Raras
Buscar doenças, sintomas, genes...
Síndrome WHIM
ORPHA:51636CID-10 · D81.8CID-11 · 4A00.YOMIM 193670DOENÇA RARA

Deficiência imunológica congênita autossômica dominante caracterizada por retenção anormal de neutrófilos maduros na medula óssea (mielcatexia) e hipogamaglobulinemia ocasional, associada a um risco aumentado de infecções bacterianas e suscetibilidade a lesões induzidas pelo papilomavírus humano (HPV) (verrugas cutâneas, displasia genital e carcinoma invasivo da mucosa).

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Introdução

O que você precisa saber de cara

📋

Deficiência imunológica congênita autossômica dominante caracterizada por retenção anormal de neutrófilos maduros na medula óssea (mielcatexia) e hipogamaglobulinemia ocasional, associada a um risco aumentado de infecções bacterianas e suscetibilidade a lesões induzidas pelo papilomavírus humano (HPV) (verrugas cutâneas, displasia genital e carcinoma invasivo da mucosa).

Pesquisas ativas
1 ensaio
5 total registrados no ClinicalTrials.gov
Publicações científicas
206 artigos
Último publicado: 2026 Mar 30

Escala de raridade

CLASSIFICAÇÃO ORPHANET · BRASIL 2024
<1 / 1 000 000
Ultra-rara
<1/50k
Muito rara
1/20k
Rara
1/10k
Pouco freq.
1/5k
Incomum
1/2k
Prevalência
0.0
Worldwide
Casos conhecidos
65
pacientes catalogados
Início
Adolescent
+ adult, childhood
🏥
SUS: Sem cobertura SUSScore: 0%
CID-10: D81.8
Você se identifica com essa condição?
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Entender a doença

Do básico ao detalhe, leia no seu ritmo

Preparando trilha educativa...

Sinais e sintomas

O que aparece no corpo e com que frequência cada sintoma acontece

Partes do corpo afetadas

🫁
Pulmão
5 sintomas
🩸
Sangue
4 sintomas
🧠
Neurológico
2 sintomas
🦴
Ossos e articulações
2 sintomas
🧬
Pele e cabelo
1 sintomas
🛡️
Imunológico
1 sintomas

+ 24 sintomas em outras categorias

Características mais comuns

90%prev.
Contagem total de neutrófilos diminuída
Muito frequente (99-80%)
90%prev.
Linfopenia
Muito frequente (99-80%)
90%prev.
Anormalidade da morfologia do neutrófilo
Muito frequente (99-80%)
90%prev.
Hipercelularidade da medula óssea
Muito frequente (99-80%)
90%prev.
Mielocatexia
Muito frequente (99-80%)
55%prev.
Pneumonia
Frequente (79-30%)
40sintomas
Muito frequente (5)
Frequente (8)
Ocasional (11)
Muito raro (10)
Sem dados (6)

Os sintomas variam de pessoa para pessoa. Abaixo estão as 40 características clínicas mais associadas, ordenadas por frequência.

Contagem total de neutrófilos diminuídaDecreased total neutrophil count
Muito frequente (99-80%)90%
LinfopeniaLymphopenia
Muito frequente (99-80%)90%
Anormalidade da morfologia do neutrófiloAbnormality of neutrophil morphology
Muito frequente (99-80%)90%
Hipercelularidade da medula ósseaBone marrow hypercellularity
Muito frequente (99-80%)90%
MielocatexiaMyelokathexis
Muito frequente (99-80%)90%

Linha do tempo da pesquisa

Publicações por ano — veja quando o interesse científico cresceu
Anos de pesquisa1desde 2026
Total histórico206PubMed
Últimos 10 anos135publicações
Pico202421 papers
Linha do tempo
2026Hoje · 2026🧪 2004Primeiro ensaio clínico📈 2024Ano de pico
Publicações por ano (últimos 10 anos)

Encontrou um erro ou informação desatualizada? Sugira uma correção →

Genética e causas

O que está alterado no DNA e como passa nas famílias

Genes associados

1 gene identificado com associação a esta condição. Padrão de herança: Autosomal dominant, Autosomal recessive, Not applicable.

CXCR4C-X-C chemokine receptor type 4Disease-causing germline mutation(s) (gain of function) inAltamente restrito
FUNÇÃO

Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10074102, PubMed:10452968, PubMed:10644702, PubMed:10825158, PubMed:18799424, PubMed:20048153, PubMed:20505072, PubMed:24912431, PubMed:28978524, PubMed:8752280, PubMed:8752281). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstr

LOCALIZAÇÃO

Cell membraneCell junctionEarly endosomeLate endosomeLysosome

VIAS BIOLÓGICAS (7)
G alpha (i) signalling eventsChemokine receptors bind chemokinesFormation of definitive endodermSignaling by ROBO receptorsDevelopmental Lineage of Multipotent Pancreatic Progenitor Cells
MECANISMO DE DOENÇA

WHIM syndrome 1

An autosomal dominant immunologic 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.

EXPRESSÃO TECIDUAL(Ubíquo)
Sangue
419.9 TPM
Baço
410.7 TPM
Intestino delgado
170.7 TPM
Pulmão
126.9 TPM
Glândula adrenal
80.9 TPM
OUTRAS DOENÇAS (1)
WHIM syndrome 1
HGNC:2561UniProt:P61073

Medicamentos aprovados (FDA)

1 medicamento encontrado nos registros da FDA americana.

💊 XOLREMDI (MAVORIXAFOR)
Ver no DailyMed/FDA

Variantes genéticas (ClinVar)

60 variantes patogênicas registradas no ClinVar.

🧬 CXCR4: NM_003467.3(CXCR4):c.990_991del (p.Lys331fs) ()
🧬 CXCR4: NM_003467.3(CXCR4):c.977_978del (p.Leu326fs) ()
🧬 CXCR4: NM_003467.3(CXCR4):c.979_980insG (p.Lys327fs) ()
🧬 CXCR4: NM_003467.3(CXCR4):c.986_990del (p.Leu329fs) ()
🧬 CXCR4: NM_003467.3(CXCR4):c.997A>T (p.Lys333Ter) ()
Ver todas no ClinVar

Classificação de variantes (ClinVar)

Distribuição de 33 variantes classificadas pelo ClinVar.

28
5
Patogênica (84.8%)
VUS (15.2%)
VARIANTES MAIS SIGNIFICATIVAS
CXCR4: NM_003467.3(CXCR4):c.977_978del (p.Leu326fs) [Pathogenic]
CXCR4: NM_003467.3(CXCR4):c.979_980insG (p.Lys327fs) [Pathogenic]
CXCR4: NM_003467.3(CXCR4):c.986_990del (p.Leu329fs) [Pathogenic]
CXCR4: NM_003467.3(CXCR4):c.997A>T (p.Lys333Ter) [Likely pathogenic]
CXCR4: NM_003467.3(CXCR4):c.1016_1017dup (p.Val340fs) [Pathogenic]

Diagnóstico

Os sinais que médicos procuram e os exames que confirmam

Carregando...

Tratamento e manejo

Remédios, cuidados de apoio e o que precisa acompanhar

Pipeline de tratamentos
Pipeline regulatório — de medicamentos já aprovados a drogas em pesquisa exploratória.
3Fase 31
2Fase 21
·Pré-clínico1
Medicamentos catalogadosEnsaios clínicos· 0 medicamentos · 3 ensaios
Carregando informações de tratamento...

Onde tratar no SUS

Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)

🇧🇷 Atendimento SUS — Síndrome WHIM

🗺️

Selecione um estado ou use sua localização para ver resultados.

Dados de DATASUS/CNES, SBGM, ABNeuro e Ministério da Saúde. Sempre confirme a disponibilidade diretamente com o estabelecimento.

Pesquisa ativa

Ensaios clínicos abertos e novidades científicas recentes

Pesquisa e ensaios clínicos

5 ensaios clínicos encontrados, 1 ativos.

Distribuição por fase
Ver todos no ClinicalTrials.gov
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Publicações mais relevantes

Timeline de publicações
126 papers (10 anos)
#1

A patient with WHIM syndrome presenting relatively low TREC, KREC, and housekeeping gene levels by newborn screening -a case report and the literature review.

Immunological medicine2026 Mar 07

WHIM syndrome is the inborn errors of immunity characterized by warts, hypogammaglobulinemia, infections, and myelokathexis, by the pathogenic variant in CXCR4. Patients with WHIM syndrome demonstrate neutropenia and lymphopenia due to the impaired migration of neutrophils and lymphocytes from the bone marrow. Diagnosis of patients with WHIM syndrome is often challenging, because some patients with WHIM syndrome do not show all characteristic four manifestations. T-cell receptor excision circle (TREC) and kappa-deleting recombination excision circle (KREC) assay is used for the screening of disease, such as severe combined immunodeficiencies and X-linked agammaglobulinemia. Several reports have shown that patients with WHIM syndrome show relatively low TREC or KREC levels, sometimes below the cut-off value. We present a patient with WHIM syndrome who developed recurrent viral and bacterial infections with myelokathexis. We assessed TREC, KREC, and a housekeeping gene marker levels at 5 days after birth and 3 years of age; although all values were relatively low, they remained above the established cut-off thresholds. We reviewed reports on TREC, KREC, and housekeeping gene levels in patients with WHIM syndrome and found that these patients generally showed relatively low levels of all three markers, with some values falling below the established cut-off thresholds.

#2

WHIM syndrome in a child without the classic tetrad: a case confirmed by de novo CXCR4 mutation.

Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology2026 Feb 02

WHIM syndrome is a rare autosomal dominant primary immunodeficiency characterized by the classical tetrad of warts, hypogammaglobulinemia, infections, and myelokathexis. The majority of cases are associated with gain-of-function mutations in the CXCR4 gene. Recent studies have expanded the clinical spectrum of the disease, revealing that only a subset of patients present with all four hallmark features. This underscores the syndrome's variable expression and the need for greater clinical awareness of its atypical forms. We report a case of a 6-year-old Saudi girl who presented with persistent neutropenia, recurrent upper respiratory infections, and an episode of thrombocytopenia following a dental procedure. She did not exhibit warts, hypogammaglobulinemia, or myelokathexis. Immunological workup revealed marked lymphopenia affecting T, B, and NK cells, while immunoglobulin levels remained within normal limits. Bone marrow findings were unremarkable. Whole-exome sequencing identified a heterozygous de novo CXCR4 frameshift mutation (c.1172_1173del), confirming the diagnosis of WHIM syndrome. The patient was clinically stable and managed conservatively with precautions. This case contributes to the evolving understanding of the clinical variability in WHIM syndrome and highlights the importance of genetic testing in patients with unexplained neutropenia and recurrent infections, even in the absence of the complete clinical tetrad.

#3

Gene therapy via CRISPR/Cas9-mediated Cxcr4 disease allele inactivation reverses leukopenia in WHIM mice.

The Journal of clinical investigation2026 Mar 02

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is an immunodeficiency caused by autosomal dominant hyperfunctional mutations in chemokine receptor CXCR4 that promote panleukopenia due to BM retention. We previously reported a preclinical gene therapy protocol involving allele-nonspecific Cxcr4 CRISPR/Cas9 inactivation, leveraging the known in vivo dominance of Cxcr4+/o (+, WT; o, inactivated) hematopoietic stem cells (HSCs) for autologous BM engraftment and leukocyte reconstitution over HSCs with other Cxcr4 genotypes. Here, we show that without BM conditioning, this approach is not able to correct leukopenia in WHIM mice. We therefore modified the protocol by adding conditioning with a nongenotoxic CD117-targeted immunotoxin, CD117-antibody-saporin-conjugate. With this change, donor-derived blood cells rapidly reached ~95% chimerism after transplantation, which was stable without adverse events. Mice receiving edited HSCs showed rapid normalization of absolute myeloid cell counts, the key blood subset responsible for WHIM syndrome. In competitive transplants using equal numbers of edited and unedited donor HSCs, over 80% of blood cells originated from the edited population, predominantly with the Cxcr4+/o genotype. These results provide proof of principle that CRISPR/Cas9-mediated inactivation of the Cxcr4 disease allele, combined with nongenotoxic HSC-targeted conditioning, may offer a safe and effective gene therapy strategy generalizable to all WHIM-causing mutations.

#4

WHIM syndrome: from mechanism to targeted therapy - advances shaping clinical care.

Current opinion in allergy and clinical immunology2026 Feb 01

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is an autosomal dominant combined immunodeficiency (CID), often caused by increased CXCR4 pathway signaling. Against early-onset hallmark of neutropenia, diagnosis is delayed due to lack of awareness, incomplete penetrance, and requirement for specialized bone marrow evaluation to detect myelokathexis. Some infants with WHIM are identified via newborn screening for low thymic emigrant T cells. Early pediatric diagnosis is associated with improved outcomes. The genetic spectrum of CXCR4 expands beyond the canonical C-terminal hotspot, with N-terminal p.D84H variant. Recent trials of oral CXCR4 antagonist demonstrated increased circulating mature neutrophils and lymphocytes, reduced infection burden, and, in some cases, wart regression. Mechanistic studies in human and murine models contribute to the understanding of the combined immunodeficiency phenotype and highlight how CXCR4 hyperactivation impairs hematopoietic stem/progenitor cell egress, leukocyte trafficking and disrupts stromal niches critical for lymphocyte development and survival. Increased awareness, opportunities for screening at birth, improved pathological and genetic diagnostics, and 2024 FDA approval of the first oral CXCR4 antagonist create practical advance in targeting WHIM syndrome. As a CID with lifetime risk for humoral deficiency, impaired antiviral defense and malignancy, WHIM warrants long-term monitoring and further investigation into broader applications of CXCR4 antagonism.

#5

Continuous Infusion of the CXCR4 Antagonist Plerixafor for WHIM Syndrome.

medRxiv : the preprint server for health sciences2025 Apr 22

WHIM (Warts, Hypogammaglobulinemia, Infections and Myelokathexis) syndrome is an ultrarare inborn error of immunity caused by heterozygous, gain-of-function CXCR4 mutations that impede leukocyte egress from bone marrow, resulting in panleukopenia. The CXCR4 antagonist plerixafor (AMD3100, Mozobil) durably reverses panleukopenia and in most WHIM patients induces wart regression; however, its short half-life requires twice daily injection. To develop a simpler, cheaper and potentially more effective method of drug delivery, we conducted a Phase 1 study of WHIM patients given plerixafor 0.02-0.08 mg/kg/d by continuous subcutaneous infusion using an OmniPod insulin pump, and assessed compliance as well as effects on blood leukocyte counts, infections, chronic skin conditions and adverse events. Six patients were treated for a total of 6.3 patient-years; one patient dropped out early for personal reasons. The drug infusion rate was adjusted to achieve a normal absolute lymphocyte count and an absolute neutrophil count >500 cells/μl in all patients. An average of 2.1 infections/patient-year occurred (range 0-4). Treatment of two infections involved brief hospitalization. On plerixafor, partial wart regression occurred in 3 of 4 patients, a single molluscum contagiosum infection regressed and a chronic post-Mohs surgical wound epithelialized. There were 3 serious adverse events, but none was attributable to the treatment. All patients preferred pump administration over syringe injection. Thus, in WHIM patients a continuous infusion pump may be a convenient, safe and potentially cost-effective means of delivering plerixafor chronically to correct panleukopenia and to improve chronic skin conditions. Clinicaltrials.gov NCT00967785.

Publicações recentes

Ver todas no PubMed

📚 EuropePMC129 artigos no totalmostrando 129

2026

A patient with WHIM syndrome presenting relatively low TREC, KREC, and housekeeping gene levels by newborn screening -a case report and the literature review.

Immunological medicine
2026

WHIM syndrome in a child without the classic tetrad: a case confirmed by de novo CXCR4 mutation.

Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology
2026

Gene therapy via CRISPR/Cas9-mediated Cxcr4 disease allele inactivation reverses leukopenia in WHIM mice.

The Journal of clinical investigation
2026

WHIM syndrome: from mechanism to targeted therapy - advances shaping clinical care.

Current opinion in allergy and clinical immunology
2025

CXCR4 antagonism corrects neutrophil abnormalities and reduces pneumonia severity in a pharmacological mouse model of CXCR2 loss-of-function-mediated neutropenia.

Frontiers in immunology
2025

Case Report: A novel CXCR4 variant (p.S341Y) in a family with a pathogenic NFKB1 variant and variable clinical manifestations.

Frontiers in immunology
2025

Immunoregulator multitasking in neurons is not just a WHIM.

Neuron
2025

Monoclonal gammopathy in WHIM syndrome can mask hypogammaglobulinemia.

The journal of allergy and clinical immunology. Global
2025

Neurodevelopmental origins of structural and psychomotor defects in CXCR4-linked primary immunodeficiency.

Neuron
2025

Game Changers: Blockbuster Small-Molecule Drugs Approved by the FDA in 2024.

Pharmaceuticals (Basel, Switzerland)
2025

Continuous Infusion of the CXCR4 Antagonist Plerixafor for WHIM Syndrome.

medRxiv : the preprint server for health sciences
2025

Clinicopathologic Features and the Spectrum of Myelokathexis in Warts, Hypogammaglobulinemia, Infections, Myelokathexis Syndrome.

Laboratory investigation; a journal of technical methods and pathology
2025

Mavorixafor: a CXCR4 antagonist for WHIM syndrome.

Immunopharmacology and immunotoxicology
2025

Mavorixafor, CXCR4 antagonist, a novel treatment for WHIM syndrome, first FDA approval 2024.

Annals of medicine and surgery (2012)
2025

Cutaneous manifestations of WHIM syndrome.

The Journal of dermatology
2025

Risk of Superficial Fungal Infections in WHIM Syndrome.

Dermatology and therapy
2025

Recalcitrant tinea capitis in WHIM syndrome.

Skin health and disease
2025

Unveiling WHIM syndrome: Mavorixafor's emerging role in immune restoration and therapy.

Clinical and experimental immunology
2024

Corrigendum: Heterogeneous phenotype of a Chinese Familial WHIM syndrome with CXCR4V340fs gain-of-function mutation.

Frontiers in immunology
2024

From phenotypic to molecular diagnosis: Insights from a clinical immunology service focused on inborn errors of immunity in Colombia.

Biomedica : revista del Instituto Nacional de Salud
2024

CXCR4 antagonism ameliorates leukocyte abnormalities in a preclinical model of WHIM syndrome.

Frontiers in immunology
2024

Heterogeneous phenotype of a Chinese Familial WHIM syndrome with CXCR4V340fs gain-of-function mutation.

Frontiers in immunology
2024

Xolremdi (Mavorixafor): a breakthrough in WHIM syndrome treatment - unraveling efficacy and safety in a rare disease frontier.

Annals of medicine and surgery (2012)
2025

Use of plerixafor for short-term management of leukopenia in a pediatric patient with WHIM syndrome.

Pediatric blood &amp; cancer
2024

CXCR4 signaling determines the fate of hematopoietic multipotent progenitors by stimulating mTOR activity and mitochondrial metabolism.

Science signaling
2024

Increased Susceptibility of WHIM Mice to Papillomavirus-induced Disease is Dependent upon Immune Cell Dysfunction.

PLoS pathogens
2024

Expanding CXCR4 variant landscape in WHIM syndrome: integrating clinical and functional data for variant interpretation.

Frontiers in immunology
2024

The complex nature of CXCR4 mutations in WHIM syndrome.

Frontiers in immunology
2024

Unexpected diagnosis of WHIM syndrome in refractory autoimmune cytopenia.

Blood advances
2024

Mavorixafor: First Approval.

Drugs
2024

Mavorixafor: a new hope for WHIM syndrome.

Blood
2024

Plerixafor for pathogen-agnostic treatment in murine thigh infection and zebrafish sepsis.

Clinical and translational science
2024

A novel transmembrane CXCR4 variant that expands the WHIM genotype-phenotype paradigm.

Blood advances
2024

CXCR4 chemokine antagonist scores a first FDA approval for WHIM syndrome.

Nature reviews. Drug discovery
2024

A phase 3 randomized trial of mavorixafor, a CXCR4 antagonist, for WHIM syndrome.

Blood
2024

CXCR4 Antagonist in HPV5-Associated Perianal Squamous-Cell Carcinoma.

The New England journal of medicine
2024

CXCR4 WHIM syndrome is a cancer predisposition condition for virus-induced malignancies.

British journal of haematology
2024

Interplay between androgen and CXCR4 chemokine signaling in myelin repair.

Acta neuropathologica communications
2024

Periodontal disease in patients with WHIM syndrome.

Journal of clinical periodontology
2024

Congenital neutropenia: From lab bench to clinic bedside and back.

Mutation research. Reviews in mutation research
2023

[Early detection of WHIM symdrome. A case report].

Revista alergia Mexico (Tecamachalco, Puebla, Mexico : 1993)
2023

A phase III randomized crossover trial of plerixafor versus G-CSF for treatment of WHIM syndrome.

The Journal of clinical investigation
2023

Gene silencing on a WHIM.

Blood
2023

Dale DC, Firkin F, Bolyard AA, et al. Results of a phase 2 trial of an oral CXCR4 antagonist, mavorixafor, for treatment of WHIM syndrome. Blood. 2020;136(26):2994-3003.

Blood
2023

Severe CD8+ T Lymphopenia in WHIM Syndrome Caused by Selective Sequestration in Primary Immune Organs.

Journal of immunology (Baltimore, Md. : 1950)
2023

Vedolizumab for children with intestinal graft-versus-host disease: a case report and literature review.

International journal of hematology
2023

Historical Cohort of Severe Congenital Neutropenia in Iran: Clinical Course, Laboratory Evaluation, Treatment, and Survival.

Journal of pediatric hematology/oncology
2023

WHIM Syndrome-linked CXCR4 mutations drive osteoporosis.

Nature communications
2023

CRISPR/Cas9-mediated Cxcr4 disease allele inactivation for gene therapy in a mouse model of WHIM syndrome.

Blood
2023

Reduced G protein signaling despite impaired internalization and β-arrestin recruitment in patients carrying a CXCR4Leu317fsX3 mutation causing WHIM syndrome.

JCI insight
2023

WHIM Syndrome: First Reported Case in a Patient of African Ancestry.

Case reports in hematology
2023

[CXCR4 as a rheostat of humoral response].

Medecine sciences : M/S
2022

Can we identify WHIM in infancy? Opportunities with the public newborn screening process.

American journal of medical genetics. Part C, Seminars in medical genetics
2022

Reactogenicity and immunogenicity of the second COVID-19 vaccination in patients with inborn errors of immunity or mannan-binding lectin deficiency.

Frontiers in immunology
2022

Dysregulated stem cell niches and altered lymphocyte recirculation cause B and T cell lymphopenia in WHIM syndrome.

Science immunology
2022

Genotype-phenotype correlations in WHIM syndrome: a systematic characterization of CXCR4WHIM variants.

Genes and immunity
2022

Disease Progression of WHIM Syndrome in an International Cohort of 66 Pediatric and Adult Patients.

Journal of clinical immunology
2022

Clinical and Hematologic Effects of Endotoxin in Warts, Hypogammaglobulinemia, Infections, and Myelokathexis Syndrome Model Mice.

ImmunoHorizons
2022

Altered CXCR4 dynamics at the cell membrane impairs directed cell migration in WHIM syndrome patients.

Proceedings of the National Academy of Sciences of the United States of America
2022

Case Report: A Novel CXCR4 Mutation in a Chinese Child With Kawasaki Disease Causing WHIM Syndrome.

Frontiers in immunology
2022

A Sherlock Approach to a Kindred With a Variable Immunohematologic Phenotype.

The journal of allergy and clinical immunology. In practice
2022

Plerixafor on a WHIM - Promise or Fantasy of a New CXCR4 Inhibitor for This Rare, but Important Syndrome?

Skin therapy letter
2022

Characterization of a new WHIM syndrome mutant reveals mechanistic differences in regulation of the chemokine receptor CXCR4.

The Journal of biological chemistry
2022

Dexamethasone Treatment for COVID-19-Related Lung Injury in an Adult with WHIM Syndrome.

Journal of clinical immunology
2021

Mesenchymal Stem/Stromal Cells Overexpressing CXCR4R334X Revealed Enhanced Migration: A Lesson Learned from the Pathogenesis of WHIM Syndrome.

Cell transplantation
2022

Multicenter Experience of Hematopoietic Stem Cell Transplantation in WHIM Syndrome.

Journal of clinical immunology
2021

Hematopoietic Multipotent Progenitors and Plasma Cells: Neighbors or Roommates in the Mouse Bone Marrow Ecosystem?

Frontiers in immunology
2021

Unusual morphological abnormality of neutrophils in a patient with SARS-CoV-2 infection.

British journal of haematology
2021

CXCR4 signaling controls dendritic cell location and activation at steady state and in inflammation.

Blood
2021

Hematologic disorder-associated Cxcr4 gain-of-function mutation leads to uncontrolled extrafollicular immune response.

Blood
2021

The negative charge of the 343 site is essential for maintaining physiological functions of CXCR4.

BMC molecular and cell biology
2021

TREC Screening for WHIM Syndrome.

Journal of clinical immunology
2020

Hematopoietic Stem Cell Niches and Signals Controlling Immune Cell Development and Maintenance of Immunological Memory.

Frontiers in immunology
2020

Results of a phase 2 trial of an oral CXCR4 antagonist, mavorixafor, for treatment of WHIM syndrome.

Blood
2020

Aberrant CXCR4 Signaling at Crossroad of WHIM Syndrome and Waldenstrom's Macroglobulinemia.

International journal of molecular sciences
2020

Incomplete Presentation of WHIM Syndrome: The Diagnostic Role of Dysmorphic Neutrophils in Bone Marrow.

Journal of pediatric hematology/oncology
2020

CXCR4 antagonist AMD3100 (plerixafor): From an impurity to a therapeutic agent.

Pharmacological research
2020

New Insights on the Emerging Genomic Landscape of CXCR4 in Cancer: A Lesson from WHIM.

Vaccines
2019

Low-level Cxcr4-haploinsufficient HSC engraftment is sufficient to correct leukopenia in WHIM syndrome mice.

JCI insight
2020

Family studies of warts, hypogammaglobulinemia, immunodeficiency, myelokathexis syndrome.

Current opinion in hematology
2019

A chemotaxis model to explain WHIM neutrophil accumulation in the bone marrow of WHIM mouse model.

Blood science (Baltimore, Md.)
2019

Abnormal Newborn Screen in a WHIM Syndrome Infant.

Journal of clinical immunology
2019

Acute myeloid leukemia arising after Hodgkin lymphoma in a patient with WHIM syndrome.

Pediatric blood &amp; cancer
2019

Case Report: Ocular toxoplasmosis in a WHIM syndrome immunodeficiency patient.

F1000Research
2019

WHIM Syndrome: from Pathogenesis Towards Personalized Medicine and Cure.

Journal of clinical immunology
2019

Enhanced Bone Marrow Homing of Natural Killer Cells Following mRNA Transfection With Gain-of-Function Variant CXCR4R334X.

Frontiers in immunology
2019

The WHIM Syndrome Is No Longer a Whim.

The journal of allergy and clinical immunology. In practice
2019

Plerixafor for the Treatment of WHIM Syndrome. Reply.

The New England journal of medicine
2019

Plerixafor for the Treatment of WHIM Syndrome.

The New England journal of medicine
2019

Cerebellar involvement in warts Hypogammaglobulinemia immunodeficiency myelokathexis patients: neuroimaging and clinical findings.

Orphanet journal of rare diseases
2019

Mozobil® (Plerixafor, AMD3100), 10 years after its approval by the US Food and Drug Administration.

Antiviral chemistry &amp; chemotherapy
2019

Acetate as a model for aspartate-based CXCR4 chemokine receptor binding of cobalt and nickel complexes of cross-bridged tetraazamacrocycles.

Dalton transactions (Cambridge, England : 2003)
2019

Long-Term Outcome of WHIM Syndrome in 18 Patients: High Risk of Lung Disease and HPV-Related Malignancies.

The journal of allergy and clinical immunology. In practice
2019

Rubella Virus-Associated Cutaneous Granulomatous Disease: a Unique Complication in Immune-Deficient Patients, Not Limited to DNA Repair Disorders.

Journal of clinical immunology
2018

Adaptive Immunodeficiency in WHIM Syndrome.

International journal of molecular sciences
2019

WHIM syndrome: Immunopathogenesis, treatment and cure strategies.

Immunological reviews
2018

Metagenomic Discovery of 83 New Human Papillomavirus Types in Patients with Immunodeficiency.

mSphere
2018

Pathological roles of the homeostatic chemokine CXCL12.

Cytokine &amp; growth factor reviews
2018

Transient Marked Increase of γδ T Cells in WHIM Syndrome After Successful HSCT.

Journal of clinical immunology
2018

Enhancement of stem cell engraftment on a WHIM.

The Journal of clinical investigation
2018

CXCR4, the master regulator of neutrophil trafficking in homeostasis and disease.

European journal of clinical investigation
2018

Cxcr4-haploinsufficient bone marrow transplantation corrects leukopenia in an unconditioned WHIM syndrome model.

The Journal of clinical investigation
2018

[Late diagnosis of WHIM sydrome].

Medicina
2018

Neutropenia, hypogammaglobulinemia, and pneumonia: A case of WHIM syndrome.

Pediatrics international : official journal of the Japan Pediatric Society
2018

Multisystem multitasking by CXCL12 and its receptors CXCR4 and ACKR3.

Cytokine
2018

Mechanisms of Sustained Neutrophilia in Patient WHIM-09, Cured of WHIM Syndrome by Chromothripsis.

Journal of clinical immunology
2017

How I treat warts, hypogammaglobulinemia, infections, and myelokathexis syndrome.

Blood
2017

Pathogenesis, diagnosis and therapeutic strategies in WHIM syndrome immunodeficiency.

Expert opinion on orphan drugs
2017

CXCL12 Mediates Aberrant Costimulation of B Lymphocytes in Warts, Hypogammaglobulinemia, Infections, Myelokathexis Immunodeficiency.

Frontiers in immunology
2017

CXCR4-Specific Nanobodies as Potential Therapeutics for WHIM syndrome.

The Journal of pharmacology and experimental therapeutics
2017

WHIM Syndrome With a Novel CXCR4 Variant in a Korean Child.

Annals of laboratory medicine
2017

Lymphoid differentiation of hematopoietic stem cells requires efficient Cxcr4 desensitization.

The Journal of experimental medicine
2017

Dysplasia of Granulocytes in a Patient with HPV Disease, Recurrent Infections, and B Lymphopenia: A Novel Variant of WHIM Syndrome?

Frontiers in pediatrics
2017

Preference of Genetic Diagnosis of CXCR4 Mutation Compared with Clinical Diagnosis of WHIM Syndrome.

Journal of clinical immunology
2017

G Protein-Coupled Receptor Kinase 3 and Protein Kinase C Phosphorylate the Distal C-Terminal Tail of the Chemokine Receptor CXCR4 and Mediate Recruitment of β-Arrestin.

Molecular pharmacology
2017

Detection of MYD88 L265P and WHIM-like CXCR4 mutation in patients with IgM monoclonal gammopathy related disease.

Annals of hematology
2017

Targeted strategies directed at the molecular defect: Toward precision medicine for select primary immunodeficiency disorders.

The Journal of allergy and clinical immunology
2016

Efficient Plasma Cell Differentiation and Trafficking Require Cxcr4 Desensitization.

Cell reports
2017

Modern management of phagocyte defects.

Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology
2016

Successful hematopoietic stem cell transplantation for myelofibrosis in an adult with warts-hypogammaglobulinemia-immunodeficiency-myelokathexis syndrome.

The Journal of allergy and clinical immunology
2016

Waldenström macroglobulinemia: biology, genetics, and therapy.

Blood and lymphatic cancer : targets and therapy
2016

CXCR4 signaling in health and disease.

Immunology letters
2016

Clinical Validation of a CXCR4 Mutation Screening Assay for Waldenstrom Macroglobulinemia.

Clinical lymphoma, myeloma &amp; leukemia
2016

WHIM Syndrome Caused by Waldenström's Macroglobulinemia-Associated Mutation CXCR4 (L329fs).

Journal of clinical immunology
2015

Chromothriptic cure of WHIM syndrome: Implications for bone marrow transplantation.

Rare diseases (Austin, Tex.)
2015

Human Immunodeficiencies Related to Defective APC/T Cell Interaction.

Frontiers in immunology
2015

Molecular Pathways: Targeting the CXCR4-CXCL12 Axis--Untapped Potential in the Tumor Microenvironment.

Clinical cancer research : an official journal of the American Association for Cancer Research
2015

Chromothriptic cure of WHIM syndrome.

Cell
2016

Primary cutaneous follicle center lymphoma in a patient with WHIM syndrome.

Journal of the European Academy of Dermatology and Venereology : JEADV

Associações

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Comunidades

Grupos ativos de quem convive com esta doença aqui no Raras

Ainda não existe comunidade no Raras para Síndrome WHIM

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Doenças relacionadas

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Referências e fontes

Bases de dados externas citadas neste artigo

Publicações científicas

Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.

  1. A patient with WHIM syndrome presenting relatively low TREC, KREC, and housekeeping gene levels by newborn screening -a case report and the literature review.
    Immunological medicine· 2026· PMID 41793776mais citado
  2. WHIM syndrome in a child without the classic tetrad: a case confirmed by de novo CXCR4 mutation.
    Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology· 2026· PMID 41629964mais citado
  3. Gene therapy via CRISPR/Cas9-mediated Cxcr4 disease allele inactivation reverses leukopenia in WHIM mice.
    The Journal of clinical investigation· 2026· PMID 41505207mais citado
  4. WHIM syndrome: from mechanism to targeted therapy - advances shaping clinical care.
    Current opinion in allergy and clinical immunology· 2026· PMID 41451822mais citado
  5. Continuous Infusion of the CXCR4 Antagonist Plerixafor for WHIM Syndrome.
    medRxiv : the preprint server for health sciences· 2025· PMID 40330596mais citado
  6. Oral CXCR4 inhibition with mavorixafor: Emerging therapeutic applications in WHIM syndrome, chronic neutropenia, oncology, and stem cell mobilization.
    Curr Res Transl Med· 2026· PMID 41936270recente
  7. Continuous Infusion of the CXCR4 Antagonist Plerixafor for WHIM Syndrome.
    J Clin Immunol· 2026· PMID 41904735recente

Bases de dados e fontes oficiais

Identificadores e referências canônicas usadas para montar este verbete.

  1. ORPHA:51636(Orphanet)
  2. OMIM OMIM:193670(OMIM)
  3. MONDO:8000006(MONDO)
  4. GARD:9297(GARD (NIH))
  5. Variantes catalogadas(ClinVar)
  6. Busca completa no PubMed(PubMed)
  7. Q1258463(Wikidata)

Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.

Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar

Síndrome WHIM
Compêndio · Raras BR

Síndrome WHIM

ORPHA:51636 · MONDO:8000006
Prevalência
<1 / 1 000 000
Casos
65 casos conhecidos
Herança
Autosomal dominant, Autosomal recessive, Not applicable
CID-10
D81.8 · Outras deficiências imunitárias combinadas
CID-11
Ensaios
1 ativos
Início
Adolescent, Adult, Childhood
Prevalência
0.0 (Worldwide)
MedGen
UMLS
C0472817
EuropePMC
Wikidata
Papers 10a
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