More detailed information about the symptoms, causes, and treatments of whim. Whim syndrome is a rare congenital immunodeficiency disease, named after its main clinical manifestations. Description and outcome of a cohort of 8 patients with. Longterm clinical remission of whim syndrome and evidence for somatic mosaicism in patient whim09 a family pedigree. Participants with a clinical diagnosis of whim syndrome must meet all of the following criteria to be eligible for study participation. Nevertheless, despite the increase in the cellularity after amd3100 treatment and b cells. Whim syndrome is a clinically variable disorder with a spectrum of features that give it its name. Genetic and rare diseases information center gard po box 8126, gaithersburg, md 208988126 toll free.
Ijms free fulltext adaptive immunodeficiency in whim. 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. Whim syndrome is an autosomal dominant combined primary immunodeficiency disease caused by mutations in the chemokine receptor cxcr4 hernandez et al. Ocular toxoplasmosis in a whim syndrome immunodeficiency patient article pdf available in f research 8. 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. Whim syndrome and oral squamous cell carcinoma article pdf available in oral surgery, oral medicine, oral pathology, oral radiology, and endodontology 1091. For gene therapy of gainoffunction autosomal dominant diseases, either correcting or deleting the disease allele is potentially curative. Dec 29, 2016 participants with a clinical diagnosis of whim syndrome must meet all of the following criteria to be eligible for study participation. 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. A dose determination and safety study of x4p001 mavorixafor. Familial occurrence of warts, hypogammaglobulinemia, infections, and myelokathexis whim syndrome, archivum immunologiae et therapiae experimentalis, 2008, pp. Whim syndrome acronym for genetic syndrome mim 193670 comprising w arts, h ypogammaglobulinemia, i nfections, and m yelokathexis.
Click on the link to view a sample search on this topic. Human papillomavirus typing of verrucae in a patient with. Cancers express a complex chemokine network influencing leucocyte infiltration and angiogenesis. Whim syndrome is an inherited immunodeficiency caused by overactivity of cxcr4, a receptor controlling production and distribution of leukocytes in bone marrow and blood. Myelokathexis is a unique form of noncyclic severe congenital neutropenia caused by accumulation of mature and degenerating neutrophils in the bone marrow. Moreover, malignant cells also express a selective repertoire of chemokine receptors that sustain their growth and. A 29yearold man was seen with recurrent warts unresponsive to prior cryotherapy, podophyllin, and imiquimod cream treatment. 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. 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. Deciphering the molecular alterations leading to disease initiation and progression is currently crucial to identify the most relevant targets for precision therapy in cancer patients.
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. 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. The m in the acronym whim refers to myelokathexis, the. Ataxia telangiectasia u2022warts, hypogammaglobulinemia, infections, and myelokathexis whim syndrome u2022severe congenital neutropenia u2022recurrent herpes simplex encephalitis u2022systemic. The long term follow up of eight patients highlights the clinical heterogeneity of this disease as well as the main therapeutic. Whim syndrome definition of whim syndrome by medical dictionary. Therefore, the diagnosis of whim syndrome may be overlooked by.
Niaid researchers discovered why a woman with whim syndrome was spontaneously cured of the disease. She underwent a therapeutic splenectomy at age 9 for the. Warts, hypogammaglobulinemia, infections and myelokathexis, which is abnormal retention of mature neutrophils in the bone marrow. Pdf chromothripsis is a catastrophic cellular event recently described in cancer in which. World map of whim syndrome find people with whim syndrome through the map. Whim syndrome symptoms, diagnosis, treatments and causes. Whim syndrome is a serious, genetic primary immunodeficiency disease that is caused by. 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. Chromothriptic cure of whim syndrome sciencedirect. A rare syndrome characterized by warts, hypogammaglobulinemia low blood gammaglobulin levels, recurring bacterial infections and myelokathexis form of neutropenia.
The impact of whim mutations on lymphocytes and adaptive immunity has received less attention than. Treatment consists on monthly injections of intravenous immunoglobulin. 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. The acronym whim resumes the main features of the syndrome. Warts, hypogammaglobulinemia, infections, and myelokathexis whim syndrome is a rare, autosomal. The whim syndrome is no longer a whim the journal of allergy. The truncation of the receptor protein results in the inability of downregulation after stimulation. They identified heterozygosity for one of these mutations 162643. 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. 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. Has a genotypeconfirmed mutation of chemokine receptor type 4 cxcr4 consistent with whim syndrome. Familial occurrence of warts, hypogammaglobulinemia. 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.
Jan 24, 2014 whim syndrome active research protocols. The acronym whim refers to warts, hypogammaglobulinemia, infections, and myelokathexis. Clinically, it is characterized by the formation of disseminated flat warts beginning in childhood. The immune system is divided into several components, the combined actions of which are responsible for defending against infectious agents. Warts, hypogammaglobulinemia, infections, and myelokathexis whim syndrome omim 193670 is a primary immunodeficiency caused by heterozygous mutations in the cxcr4 gene. Literature reports do not consistently report race. The mostaffected whim kindreds possess functional mutations in the carboxy terminus of the cxcr4 chemokine receptor 3.
Whim syndrome caused by waldenstroms macroglobulinemia. 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. Company to hold analyst day, which will also be webcast, on april 7, 2020 to discuss strategic focus on whim. We have found approximately 20 examples of whim syndrome in the literature under various designations. Pathogenesis, diagnosis and therapeutic strategies in whim. 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. The disease is primarily caused by cterminal truncation mutations of the chemokine receptor cxcr4, giving these cxcr4 whim mutants a gain of. They may also have genital and anal condyloma acuminata, and in female patients significant cervical and vulval dysplasia. It is a form of immunodeficiency disease caused by a mutation in a chemokine receptor.
Plerixafor for the treatment of whim syndrome nejm. Whim syndrome in the first half of 2019, said paula ragan, phd, president and chief executive officer of x4 pharmaceuticals. Pdf chromothriptic cure of whim syndrome researchgate. Case studies in immunology, seventh edition is intended for medical students and undergraduate and graduate students in immunology. Whim syndrome or warts, hypogammaglobulinemia, immunodeficiency, and myelokathexis syndrome is a rare congenital immunodeficiency disorder characterized by chronic noncyclic neutropenia pathophysiology. The use of prophylactic antibiotics in individuals affected with whim has not been specifically studied.
The latter refers to the retention of white cells in the marrow, which becomes hypercellular. Vaccines free fulltext new insights on the emerging. Whim syndrome is an acronym for a rare immunodeficiency disorder with each letter representing a predominant feature of the condition. Whim syndrome genetic and rare diseases information. 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.
Cxcr4specific nanobodies as potential therapeutics for. Download pdf case studies in immunology book full free. A retrospective and prospective natural history study of. If you have problems viewing pdf files, download the latest version of adobe reader. Topline data from the trial are expected in the second half of 2021.
How i treat warts, hypogammaglobulinemia, infections, and. Treatment consists on monthly injections of intravenous immunoglobulin, which may reduce the incidence. It presents major topics of immunology through a selection of clinical cases that reinforce and extend the basic science. Listing a study does not mean it has been evaluated by the u. For language access assistance, contact the ncats public information officer. Whim patients with warts characteristically have numerous warts on hands, feet and trunk. She might sweep into the room a halfhour late and everyone must drop everything theyre doing and notice her. Whim syndrome appears to be slightly more common in women than in men. A prominent and unexplained feature of whim is myelokathexis hypercellularity with apoptosis of mature myeloid. Whim syndrome is a rare primary immunodeficiency disorder, which are disorders. Whim syndrome genetic and rare diseases information center. Has signed the current approved informed consent form. Whim syndrome is a rare combined primary immunodeficiency disorder.
Whim syndrome is a rare primary immunodeficiency disorder characterized by warts, hypogammaglobulinemia, infections, and myelokathexis. The disease is primarily caused by cterminal truncation mutations of the chemokine receptor cxcr4, giving these cxcr4whim mutants a. Whim patients suffer from recurrent bacterial infections since childhood and manifest a specific susceptibility to hpv infections. Whim syndrome warts hyopogammaglobulinemia nfections. 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.
Pubmed is a searchable database of medical literature and lists journal articles that discuss whim syndrome. Whim warts, hypogammaglobulinemia, infections, and myelokathexis syndrome, a rare, inherited, primary immunodeficiency disease. Print arsanis and x4 pharmaceuticals agree to merger. Whim syndrome is an immunodeficiency disease characterized by neutropenia, hypogammaglobulinemia, and extensive human papillomavirus hpv infection. In essence, the patient had deleted the bad copy of the gene and was now cured. Nov, 2011 access to this database is free of charge. Whim syndrome nord national organization for rare disorders. Dancers dark jubilant optimistic lianes bio generous compelling honest camerons bio perceptive dynamic rooted janes bio. Clinical and genetic features of warts, hypogammaglobulinemia.
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. The disease may present at different ages with distinct complications observed in individual patients. More than five hundred of these men would never see another sunset, yet a holiday atmosphere prevailed. Most patients with whim syndrome are panleukopenic, which partially corrects if they undergo severe infection. Karyotype of a woman spontaneously cured of whim syndrome. A prominent and unexplained feature of whim is myelokathexis hypercellularity with apoptosis of mature myeloid cells in bone marrow and. Contagion and contagiousness refers to how easily the spread of whim syndrome is possible from one person to another. 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. 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. Ijms free fulltext adaptive immunodeficiency in whim syndrome. Whim syndrome is the acronym for warts, hypogammaglobulinemia. Myelokathexis is key to the clinical diagnosis of whim syndrome.
Myelokathexis is a greek neologism meaning bone marrow retention that was coined in 1964 by zuelzer to convey a mechanistic explanation for severe. Whim syndrome definition of whim syndrome by medical. However, except in whim syndrome, viral warts are not a consistent finding in these syndromes, and other typical features were absent in our patient. Warts, hypogammaglobulinemia low immunoglobulin levels, immunodeficiency susceptibility to infections, myelokathexis trapping of white blood cells in the bone marrow. Treatment consists on monthly injections of intravenous immunoglobulin, which may. 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. In familial cases, whim syndrome follows an autosomal dominant inheritance pattern 7,12. Plerixafor versus gcsf in the treatment of people with.
Hsct in whim syndrome is limited by the availability of immunologically matched donors and by the significant short and longterm risks of allotransplantation. Pdf case studies in immunology download full pdf book. Variants in rac2 have been reported in association with neutrophil immunodeficiency syndrome. 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.
The term whim is an acronym for the main manifestations of the disease. Symptoms usually begin in early childhood with recurrent bacterial infections such as respiratory infections and cellulitis. The treatment of whim syndrome is directed toward the specific symptoms that. Jci cxcr4haploinsufficient bone marrow transplantation. Almost all cases have been reported from europe and the united states. 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. In affected members of 5 unrelated families with whim syndrome, hernandez et al. 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. The first example of a human immunologic disease caused. Whim syndrome myelokathexis reproduced in the nodscid mouse. 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. Each case history is preceded by essential scientific facts about the immunological mechanisms o. X4 pharmaceuticals provides corporate update and reports. 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.
Whim syndrome whim is a congenital immune deficiency with characteristic clinical features that include. Cxcr4specific nanobodies as potential therapeutics for whim. Whim syndrome is a rare primary immunodeficiency disorder characterized by four main clinical manifestations. Altered leukocyte response to cxcl12 in patients with. Description and outcome of a cohort of 8 patients with whim. 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 myelokathexis reproduced in the nodscid. In whim syndrome, mutations of cxcr4 have been demonstrated to predispose for hpv infection by aberrant chemokine receptor function. Case studies in immunology available for download and read online in other formats. The cxcr4 antagonist plerixafor corrects panleukopenia in. Whim syndrome is an autosomal dominant immunodeficiency disease caused by mutations affecting the carboxyterminus of cxcr4. 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.