A report of WHIM syndrome (myelokathexis)

Naoum, Flávio Augusto

doi:10.5581/1516-8484.20110105

Cited by 4 publications

(1 citation statement)

References 8 publications

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“…Myelokathexis (kathexis means retention), although not exclusive, is a typical feature of WHIM syndrome, a rare autosomal dominant immunodeficiency that causes peripheral neutropenia. This condition accounts for an increased myeloid:erithroid ratio in BM caused by hypercellularity of mature neutrophils, especially clustered next to the vessels that show aberrant morphology with nuclear hypersegmentation, cytoplasmic vacuolization, and separated nuclear lobes connected by bridges of chromatin ( 3 , 4 ). In literature, few other conditions, like hematological or solid neoplasia, are characterized by hypersegmentation of chromatin and early apoptosis of neutrophils ( 5 , 6 ).…”

Section: Discussion and Concluding Remarksmentioning

confidence: 99%

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

et al. 2017

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WHIM syndrome is a condition in which affected persons have chronic peripheral neutropenia, lymphopenia, abnormal susceptibility to human papilloma virus infection, and myelokathexis. Myelokathexis refers to the retention of mature neutrophils in the bone marrow (BM), which accounts for degenerative changes and hypersegmentation. Most patients present heterozygous autosomal dominant mutations of the gene encoding CXCR4. Consequently, aberrant CXCL12/CXCR4 signaling impairs the receptor downregulation causing hyperactivation (gain-of-function) that affects BM homing for myelopoiesis and lymphopoiesis and the release of neutrophils in the bloodstream. We report the case of a 26-year-old female with severe foot and hand cutaneous warts since childhood, recalcitrant genital condylomatas, bacterial infections, and intraepithelial cervical neoplasia. Laboratory tests revealed severe B lymphopenia and HPV high and low risk types. HIV testing was negative. Not only CXCR4 but also GATA2, NEMO, and CD40L gene mutations were excluded. BM smears revealed, in the presence of a normal cellularity, hyperplasia of myeloid cells (MPO positive) and karyorrhexis, especially in neutrophils and eosinophils. Of note, neutrophils with altered lobation of nuclei connected by long thin chromatin filaments were observed. Our patient presented a clinical and histological picture reminiscent of WHIM in the presence of normal peripheral neutrophil counts and wild-type CXCR4 gene. Although the BM did not reveal a classical pattern of myelokathexis, the observation of consistent signs of neutrophil dysplasia has fuelled the hypothesis of a novel WHIM variant or a novel immunodeficiency. We speculate that abnormalities that affect CXCR4/CXCL12 pair, including GRK levels or activity, might be responsible for this WHIM-like disorder.

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Section: Discussion and Concluding Remarksmentioning

confidence: 99%

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

et al. 2017

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

et al. 2022

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Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 (CXCR4) gene. We characterize a unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct CXCR4 genetic variants within our cohort, 11 were novel pathogenic variants affecting 15 individuals (23%). All variants affect the same CXCR4 region and impair CXCR4 internalization resulting in hyperactive signaling. The median age of diagnosis in our cohort (5.5 years) indicates WHIM syndrome can commonly present in childhood, although some patients are not diagnosed until adulthood. The prevalence and mean age of recognition and/or onset of clinical manifestations within our cohort were infections 88%/1.6 years, neutropenia 98%/3.8 years, lymphopenia 88%/5.0 years, and warts 40%/12.1 years. However, we report greater prevalence and variety of autoimmune complications of WHIM syndrome (21.2%) than reported previously. Patients with versus without family history of WHIM syndrome were diagnosed earlier (22%, average age 1.3 years versus 78%, average age 5 years, respectively). Patients with a family history of WHIM syndrome also received earlier treatment, experienced less hospitalization, and had less end-organ damage. This observation reinforces previous reports that early treatment for WHIM syndrome improves outcomes. Only one patient died; death was attributed to complications of hematopoietic stem cell transplantation. The variable expressivity of WHIM syndrome in pediatric patients delays their diagnosis and therapy. Early-onset bacterial infections with severe neutropenia and/or lymphopenia should prompt genetic testing for WHIM syndrome, even in the absence of warts.

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Pediatric myelodysplastic syndrome

Babcock

Calvo

2023

Seminars in Diagnostic Pathology

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A report of WHIM syndrome (myelokathexis)

Cited by 4 publications

References 8 publications

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

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

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

Pediatric myelodysplastic syndrome

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