Most patients with whim syndrome are panleukopenic, which partially corrects if they undergo severe infection. To test whether there may be an advantage of one approach over the other for whim warts, hypogammaglobulinemia, infections, and myelokathexis syndrome a primary immunodeficiency disorder caused by gainoffunction autosomal dominant mutations in. For language access assistance, contact the ncats public information officer. Treatment consists on monthly injections of intravenous immunoglobulin, which may. Nov, 2011 access to this database is free of charge. Whim syndrome is an acronym for a rare immunodeficiency disorder with each letter representing a predominant feature of the condition. Pubmed is a searchable database of medical literature and lists journal articles that discuss whim syndrome. Epidermodysplasia verruciformis ev, first described in 1922 by lewandowsky and lutz, 1 is a rare genodermatosis characterized by a generalized infection with evspecific human papillomaviruses hpvs. Description and outcome of a cohort of 8 patients with. The case is interesting because the patient exemplifies widely known aspects of the disease, demonstrating classic features of whim syndrome, while at the same time manifests aspects of the syndrome which clinicians unfamiliar with the disease may not be aware of such as biological combined immune deficiency or a history of tetralogy of fallot.
In this investigatorinitiated, openlabel study, three severely affected patients with whim syndrome who could not receive gcsf were treated with lowdose plerixafor, a cxcr4 antagonist, for 19. How i treat warts, hypogammaglobulinemia, infections, and. A retrospective and prospective natural history study of patients with whim syndrome the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Whim syndrome is the acronym for warts, hypogammaglobulinemia. A prominent and unexplained feature of whim is myelokathexis hypercellularity with apoptosis of mature myeloid cells in bone marrow and. Pdf chromothriptic cure of whim syndrome researchgate. In essence, the patient had deleted the bad copy of the gene and was now cured. We identified a whim patient cured by chromothripsis chromosome shattering that fortuitously deleted the abnormal copy of the cxcr4 gene in a single hematopoietic stem cell, which then took over the bone marrow and restored. Description and outcome of a cohort of 8 patients with whim.
Whim syndrome is an immunodeficiency disease characterized by neutropenia, hypogammaglobulinemia, and extensive human papillomavirus hpv infection. Topline data from the trial are expected in the second half of 2021. Chromothriptic cure of whim syndrome sciencedirect. The term whim is an acronym for the main manifestations of the disease. Jci cxcr4haploinsufficient bone marrow transplantation. A retrospective and prospective natural history study of. A prominent and unexplained feature of whim is myelokathexis hypercellularity with apoptosis of mature myeloid. Whim syndrome caused by waldenstroms macroglobulinemia. Almost all cases have been reported from europe and the united states. Whim syndrome ws, a rare congenital neutropenia due to mutations of the cxcr4 chemokine receptor, is associated with human papillomavirus hpvinduced warts, hypogammaglobulinemia, bacterial infections and myelokathexis. More than five hundred of these men would never see another sunset, yet a holiday atmosphere prevailed.
Whim syndrome is a rare combined primary immunodeficiency disorder. The past medical history revealed that whim 09 was in fact the first patient ever described with myelokathexis, the key hematopathologic feature in whim syndrome, reported in two articles published in the new england journal of medicine nejm in 1964 krill et al. It is a form of immunodeficiency disease caused by a mutation in a chemokine receptor. Has signed the current approved informed consent form. In affected members of 5 unrelated families with whim syndrome, hernandez et al. Company to hold analyst day, which will also be webcast, on april 7, 2020 to discuss strategic focus on whim. Whim syndrome is a rare congenital immunodeficiency disease, named after its main clinical manifestations. The acronym whim resumes the main features of the syndrome.
Whim syndrome is a rare primary immunodeficiency disorder, which are disorders. Warts, hypogammaglobulinemia, infections, and myelokathexis whim syndrome omim 193670 is a primary immunodeficiency caused by heterozygous mutations in the cxcr4 gene. Whim syndrome is a rare primary immunodeficiency disorder characterized by four main clinical manifestations. Myelokathexis is a greek neologism meaning bone marrow retention that was coined in 1964 by zuelzer to convey a mechanistic explanation for severe. Aug 31, 2006 whim w arts, h ypogammaglobulinemia, recurrent bacterial i nfection, and m yelokathexis syndrome is a rare immunodeficiency caused in many cases by autosomal dominant cterminal truncation mutations in the chemokine receptor cxcr4. Clinically, it is characterized by the formation of disseminated flat warts beginning in childhood. Human papillomavirus typing of verrucae in a patient with. Whim syndrome or warts, hypogammaglobulinemia, immunodeficiency, and myelokathexis syndrome is a rare congenital immunodeficiency disorder characterized by chronic noncyclic neutropenia pathophysiology. Whim syndrome is caused by mutations of the cxcr4 gene that are inherited as an autosomal dominant trait. Her white blood cells were missing a large portion of chromosome 2, where the mutated whim allele resides. Cxcr4specific nanobodies as potential therapeutics for whim. Whim syndrome is an autosomal dominant combined primary immunodeficiency disease caused by mutations in the chemokine receptor cxcr4 hernandez et al.
Listing a study does not mean it has been evaluated by the u. Case studies in immunology available for download and read online in other formats. She underwent a therapeutic splenectomy at age 9 for the. Whim syndrome whim is a congenital immune deficiency with characteristic clinical features that include. The patient had been diagnosed in 2004 as having whim syndrome a primary immunodeficiency manifesting as warts, hypogammaglobulinemia, infections, and myelokathexis 1 after a hospital admission for recurrent pneumonia, leukopenia, and anemia. It presents major topics of immunology through a selection of clinical cases that reinforce and extend the basic science. The acronym whim refers to warts, hypogammaglobulinemia, infections, and myelokathexis. Jan 24, 2014 whim syndrome active research protocols. Hsct in whim syndrome is limited by the availability of immunologically matched donors and by the significant short and longterm risks of allotransplantation. Whim syndrome in the first half of 2019, said paula ragan, phd, president and chief executive officer of x4 pharmaceuticals. Print arsanis and x4 pharmaceuticals agree to merger. Dancers dark jubilant optimistic lianes bio generous compelling honest camerons bio perceptive dynamic rooted janes bio.
Whim syndrome genetic and rare diseases information. Clinical and genetic features of warts, hypogammaglobulinemia. Treatment consists on monthly injections of intravenous immunoglobulin. Familial occurrence of warts, hypogammaglobulinemia. Jul 16, 2019 whim syndrome is a rare combined primary immunodeficiency disease named by acronym for the diagnostic tetrad of warts, hypogammaglobulinemia, infections, and myelokathexis.
Whim syndrome is a rare primary immunodeficiency disorder characterized by warts, hypogammaglobulinemia, infections, and myelokathexis. Chemokine receptors are gpcrs that are critically involved in leukocyte migration, and their mutation can lead to altered signaling and migratory behavior, leading to immune system impairment. Jul 17, 2019 the case is interesting because the patient exemplifies widely known aspects of the disease, demonstrating classic features of whim syndrome, while at the same time manifests aspects of the syndrome which clinicians unfamiliar with the disease may not be aware of such as biological combined immune deficiency or a history of tetralogy of fallot. The first example of a human immunologic disease caused.
Cxcr4specific nanobodies as potential therapeutics for. These chromosome pairings, which are from her white blood cells, show a normal chromosome 2 on the left, and a truncated chromosome 2 on the right. Nevertheless, despite the increase in the cellularity after amd3100 treatment and b cells. Whim syndrome myelokathexis reproduced in the nodscid. The cxcr4 antagonist plerixafor corrects panleukopenia in. In whim syndrome, mutations of cxcr4 have been demonstrated to predispose for hpv infection by aberrant chemokine receptor function. Moreover, malignant cells also express a selective repertoire of chemokine receptors that sustain their growth and. The impact of whim mutations on lymphocytes and adaptive immunity has received less attention than. They may also have genital and anal condyloma acuminata, and in female patients significant cervical and vulval dysplasia. Whim syndrome definition of whim syndrome by medical dictionary. Whim syndrome whim is an autosomal dominant inheritance immune deficiency that in most kindreds is caused by a gain in function mutation hyperactivity with failure to down regulate in cxc chemokine receptor 4 cxcr4.
The latter refers to the retention of white cells in the marrow, which becomes hypercellular. Vaccines free fulltext new insights on the emerging. The treatment of whim syndrome is directed toward the specific symptoms that. Whimw arts, h ypogammaglobulinemia, recurrent bacterial i nfection, and m yelokathexis syndrome is a rare immunodeficiency caused in many cases by autosomal dominant cterminal truncation mutations in the chemokine receptor cxcr4. Ijms free fulltext adaptive immunodeficiency in whim syndrome. To characterize novel genetic causes of the syndrome, we recruited a pediatric patient with possible whim syndrome, performed cxcr4 gene sequencing and compared his clinical phenotype and cxcr4 tail amino acid sequences with other patients with whim syndrome carrying. Whim syndrome symptoms, diagnosis, treatments and causes. Whim syndrome is an inherited immunodeficiency caused by overactivity of cxcr4, a receptor controlling production and distribution of leukocytes in bone marrow and blood.
Mar 22, 2017 a retrospective and prospective natural history study of patients with whim syndrome the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Karyotype of a woman spontaneously cured of whim syndrome. In familial cases, whim syndrome follows an autosomal dominant inheritance pattern 7,12. Pathogenesis, diagnosis and therapeutic strategies in whim. Whim patients suffer from recurrent bacterial infections since childhood and manifest a specific susceptibility to hpv infections. Warts, hypogammaglobulinemia, infections and myelokathexis, which is abnormal retention of mature neutrophils in the bone marrow. X4 pharmaceuticals provides corporate update and reports.
The use of prophylactic antibiotics in individuals affected with whim has not been specifically studied. Whim syndrome warts hyopogammaglobulinemia nfections. Warts, hypogammaglobulinemia low immunoglobulin levels, immunodeficiency susceptibility to infections, myelokathexis trapping of white blood cells in the bone marrow. Warts, hypogammaglobulinemia, infections, and myelokathexis whim syndrome is a rare, autosomal. Symptoms usually begin in early childhood with recurrent bacterial infections such as respiratory infections and cellulitis.
The disease is primarily caused by cterminal truncation mutations of the chemokine receptor cxcr4, giving these cxcr4whim mutants a. If you have problems viewing pdf files, download the latest version of adobe reader. Plerixafor versus gcsf in the treatment of people with. The long term follow up of eight patients highlights the clinical heterogeneity of this disease as well as the main therapeutic.
Treatment consists on monthly injections of intravenous immunoglobulin, which may reduce the incidence. The long term follow up of eight patients highlights the clinical heterogeneity of this disease as well as the main therapeutic approaches and remaining challenges in the. Plerixafor versus gcsf in the treatment of people with whim syndrome the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Myelokathexis is a unique form of noncyclic severe congenital neutropenia caused by accumulation of mature and degenerating neutrophils in the bone marrow. The m in the acronym whim refers to myelokathexis, the. Cancers express a complex chemokine network influencing leucocyte infiltration and angiogenesis. Whim syndrome nord national organization for rare disorders. Ocular toxoplasmosis in a whim syndrome immunodeficiency patient article pdf available in f research 8. Whim syndrome is a primary immunodeficiency disorder, one of a group of disorders characterized by irregularities in the cell development andor cell maturation process of the immune system. World map of whim syndrome find people with whim syndrome through the map. The truncation of the receptor protein results in the inability of downregulation after stimulation. The whim syndrome is no longer a whim the journal of allergy. Participants with a clinical diagnosis of whim syndrome must meet all of the following criteria to be eligible for study participation.
Whim warts, hypogammaglobulinemia, infections, and myelokathexis syndrome, a rare, inherited, primary immunodeficiency disease. Case studies in immunology, seventh edition is intended for medical students and undergraduate and graduate students in immunology. Each case history is preceded by essential scientific facts about the immunological mechanisms o. Whim syndrome and oral squamous cell carcinoma article pdf available in oral surgery, oral medicine, oral pathology, oral radiology, and endodontology 1091. Pdf case studies in immunology download full pdf book. Whim syndrome is an autosomal dominant immunodeficiency disease caused by mutations affecting the carboxyterminus of cxcr4. She might sweep into the room a halfhour late and everyone must drop everything theyre doing and notice her. Niaid researchers discovered why a woman with whim syndrome was spontaneously cured of the disease. Myelokathexis is key to the clinical diagnosis of whim syndrome. More detailed information about the symptoms, causes, and treatments of whim.
The disease may present at different ages with distinct complications observed in individual patients. We have found approximately 20 examples of whim syndrome in the literature under various designations. The mostaffected whim kindreds possess functional mutations in the carboxy terminus of the cxcr4 chemokine receptor 3. Download pdf case studies in immunology book full free. Whim syndrome definition of whim syndrome by medical. Whim syndrome appears to be slightly more common in women than in men. Has a genotypeconfirmed mutation of chemokine receptor type 4 cxcr4 consistent with whim syndrome.
Whim patients with warts characteristically have numerous warts on hands, feet and trunk. The immune system is divided into several components, the combined actions of which are responsible for defending against infectious agents. Whim syndrome is a serious, genetic primary immunodeficiency disease that is caused by. The patient reported that from childhood through age 38, she had had many serious infections, often requiring hospitalization, but then none in the 20 subsequent years. They identified heterozygosity for one of these mutations 162643.
Altered leukocyte response to cxcl12 in patients with. Plerixafor for the treatment of whim syndrome nejm. Therefore, the diagnosis of whim syndrome may be overlooked by. Ijms free fulltext adaptive immunodeficiency in whim. Whim syndrome results from autosomal dominant mutations in the gene for the chemokine receptor, cxcr4, resulting in a carboxyterminus truncation of the receptor of between ten and 19 residues. Whim syndrome acronym for genetic syndrome mim 193670 comprising w arts, h ypogammaglobulinemia, i nfections, and m yelokathexis. Familial occurrence of warts, hypogammaglobulinemia, infections, and myelokathexis whim syndrome, archivum immunologiae et therapiae experimentalis, 2008, pp.
However, except in whim syndrome, viral warts are not a consistent finding in these syndromes, and other typical features were absent in our patient. Pdf chromothripsis is a catastrophic cellular event recently described in cancer in which. For gene therapy of gainoffunction autosomal dominant diseases, either correcting or deleting the disease allele is potentially curative. Click on the link to view a sample search on this topic. Whim syndrome myelokathexis reproduced in the nodscid mouse. Whim syndrome is due to heterozygous mutations affecting the cterminus of cxcr4, a chemokine receptor mapped on 2q21 locus and expressed by both hematopoietic and nonhematopoietic cells. Whim syndrome is a clinically variable disorder with a spectrum of features that give it its name. Early diagnosis and aggressive medical management are very important for individuals with whim syndrome treatment of the condition currently includes gcsf a medication that stimulates the production of neutrophils. Genetic and rare diseases information center gard po box 8126, gaithersburg, md 208988126 toll free. Variants in rac2 have been reported in association with neutrophil immunodeficiency syndrome. The disease is primarily caused by cterminal truncation mutations of the chemokine receptor cxcr4, giving these cxcr4 whim mutants a gain of. Literature reports do not consistently report race.
Warts, hypogammaglobulinemia, infections, and myelokathexis whim syndrome is a rare, autosomal dominant, combined immunodeficiency disorder caused by mutations in the cterminus of cxcr4 that prevent receptor downregulation and therefore result in pathologically increased signaling. Ataxia telangiectasia u2022warts, hypogammaglobulinemia, infections, and myelokathexis whim syndrome u2022severe congenital neutropenia u2022recurrent herpes simplex encephalitis u2022systemic. A 29yearold man was seen with recurrent warts unresponsive to prior cryotherapy, podophyllin, and imiquimod cream treatment. A dose determination and safety study of x4p001 mavorixafor.
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