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. Whim syndrome or wart, hypogammaglobulinemia, infection, and myelokathexis syndrome is a rare congenital immunodeficiency disorder characterized by chronic noncyclic neutropenia. These mutations confer an increased leukocyte response to the cxcr4ligand cxcl12, resulting in abnormal homeostasis of many leukocyte types, including neutrophils and lymphocytes. Warts, hypogammaglobulinemia, infections, and myelokathexis. Warts, hypogammaglobulinemia, infections, myelokathexis whim syndrome is a genetic disease that is caused by heterozygous mutations of the cxcr4 gene. Women with whim syndrome may have normal pregnancy and delivery, but whether the children are affected depends on the type of heredity of whim syndrome. Pdf chromothripsis is a catastrophic cellular event recently described in cancer in which chromosomes undergo massive deletion and.
Clinic program the association for x and y chromosome. Whim syndrome is a rare congenital immunodeficiency disease, named after its main. The first example of a human immunologic disease caused by. The term whim is an acronym for the main manifestations of the disease. The only link i have managed to find which says about the the slight difference between on a whim and at whim is the link you provided. Whim is an acronym for some of the characteristic symptoms of the disorder warts, hypogammaglobulinemia, infections, and myelokathexis. 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. 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. The cxcr4 mutations in whim syndrome impair the stability of the tcell immunologic synapse article pdf available in blood 1225 june 20 with 94 reads how we measure reads. Chromothripsis chromosomal shattering resulted in clinical cure of a patient with a rare immunode. Description and outcome of a cohort of 8 patients with. Whim syndrome is extremely rare, with 65 cases reported worldwide to date. Nov, 2011 a collection of disease information resources and questions answered by our genetic and rare diseases information specialists for whim syndrome. Whim syndrome is a serious, genetic primary immunodeficiency disease that is caused by a mutation in the cxcr4 receptor, the precise pathway targeted by x4p001.
Here, we report a case in which chromothripsis spontaneously cured a patient with whim syndrome, an autosomal dominant combined immunodeficiency. Whim syndrome is a rare autosomal dominant primary immunodeficiency disorder characterized by warts, hypogammaglobulinemia, recurrent infections, and myelokathexis it is caused by mutations usually gainoffunction in the cxcr4 gene, which result in. You must there are over 200,000 words in our free online dictionary, but you are looking for one thats only in the merriamwebster unabridged dictionary. Symptoms usually begin in early childhood with recurrent bacterial infections such as respiratory infections and cellulitis. Print arsanis and x4 pharmaceuticals agree to merger. Our program was inspired by the goal of helping children and families to. Download pdf case studies in immunology book full free.
The full article can be read here, at business wire. Paula ragan, x4s president and chief executive officer, will maintain this role and the. 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 09 to engraft can be attributed to the loss of one cxcr4 allele in that cell. Given the rarity of patients with whim syndrome, the jeffery modell foundation and x4 pharmaceuticals are sponsoring a genetic screening study to better understand the genetics of patients with whim syndrome and its.
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. Beware and be informed before you consider purchasing the whim. Picture of a horsepowered whim used to wind the cables on to work the mine between the depth of 50 feet to 500 feet photo taken at gympie, queensland, australia. Whim syndrome is caused by mutations of the cxcr4 gene that are inherited as an autosomal dominant trait. Results cure of a patient with whim syndrome the index patient, designated whim 09, is a white female who presented at age 58 to the nih requesting evaluation for herself and two of her three daughters, designated whim 10 age 21. Myelokathexis and whim syndrome ad bone marrow myelokathexis warts, hypogammaglobulinaemia, infections, and myelokathexis causing neutropenia shwachmandiamond syndrome ar bone marrow failure neutropenia due to bone marrow failure, pancreatic insu. Whim syndrome could be due to a decreased internalization of mutated. Pdf case studies in immunology download full pdf book. The treatment of whim syndrome is directed toward the specific symptoms that are. Of the 60 known individuals with whim syndrome, 29 of whom are patients at the nih, there had been no record of a patient recovering. If you have problems viewing pdf files, download the.
Plerixafor versus gcsf in the treatment of people with whim. Background epidermodysplasia verruciformis ev is a rare genodermatosis associated with infections with specific human papillomaviruses hpvs belonging to the. Whim syndrome genetic and rare diseases information. Chromothriptic cure of whim syndrome sciencedirect. Sep 25, 2017 videoin this video, i tell you everything you need to know about the harleydavidson wireless headset interface module whim for the boom box infotainment system. Arsanis, x4 pharmaceuticals announce merger deal with rare. Whim syndrome is an autosomal dominant combined primary immunodeficiency disease caused by mutations in the chemokine receptor cxcr4 hernandez et al. Whim syndrome whim is a congenital immune deficiency with characteristic clinical features that include. It is a form of immunodeficiency disease caused by a mutation in a chemokine receptor.
Whim syndrome is a rare primary immunodeficiency disorder characterized by four main clinical manifestations. In this genetic form of whim syndrome, impaired cxcr4 desensitization. Cxcr4specific nanobodies as potential therapeutics for whim. Pdf the cxcr4 mutations in whim syndrome impair the. The syndrome of warts, hypogammaglobulinemia, immunodeficiency, and myelokathexis whim. Warts are superficial viral infections of the skin that are extremely common in children. Pdf whim syndrome with a novel cxcr4 variant in a korean child. With the breakup of the soviet union in 1991, moscow lost some two million square miles of sovereign territory. Whim syndrome is a rare, autosomal dominant immunodeficiency which is named for the four key manifestations. As of today march 29 2011, i have been informed by a very reliable source that although the current plan is to merge aspergers syndrome with autism in dsm v, resulting in its deletion from dsm v, there is considerable debate over whether this is the appropriate course of action.
The infection usually lasts more than 1 year and can be moderately contagious in specific settings. Diagnosisrelated group drg systems used internationally. Whiles definition of whiles by the free dictionary. Treatment with gcsf 5 gkg per day subcutaneously was initiated after confirmation of diagnosis leading to an increase in neutrophil count to 550 cellsl after. Diagnosis patients exhibit increased susceptibility to bacterial and viral infections, especially from common serotype human papilloma virus, resulting in warts on. Fda for the treatment of whim syndrome treatment is directed toward the. Harley wireless headset interface modulewhimproblems. Pathogenesis is mediated by cxcr4 hyperfunction, leading to increased responsiveness to its unique ligand cxcl12 also known as sdf1. Treatment consists on monthly injections of intravenous immunoglobulin.
Whim syndrome symptoms, diagnosis, treatments and causes. Whim syndrome warts hyopogammaglobulinemia nfections. Description of the business of x4 pharmaceuticals, inc. Somatic mutations in myd88 and cxcr4 are determinants of. Whim syndrome is a serious, genetic primary immunodeficiency disease that is caused by a mutation in the cxcr4 receptor, the precise pathway targeted by. Familial occurrence of warts, hypogammaglobulinemia. A phase 1 clinical trial of longterm, lowdose treatment of whim syndrome with the cxcr4 antagonist plerixafor. Immunoglobulin replacement therapy and prophylactic antibiotic treatment may. 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.
Whim syndrome is usually caused by autosomal dominant mutations in the g proteincoupled chemokine receptor cxcr4 that impair desensitization, resulting in enhanced and prolonged g protein and. Accordingly, cxcr4 antagonists have shown promise as mechanismbased treatments in phase 1 clinical trials. Myelokathexis is a greek neologism meaning bone marrow retention that was coined in 1964 by zuelzer to convey a mechanistic explanation for severe. Pdf chromothriptic cure of whim syndrome researchgate. Mar 01, 2020 whim whim auditions for the 20202021 season will be held in seattle on sunday, march 1, 2020 from noon 4pm at the cornish college kerry hall 710 e roy st, and in new york city on saturday, march 7, 2020 from 2pm 6pm at gibney union square 890 broadway.
Warts hypogammaglobulinemia immunodeficiency myelokathexis whim syndrome is a rare primary immunodeficiency characterized by recurrent bacterial infections, severe congenital neutropenia, with lymphopenia and monocytopenia, associated with myelokathexis in the bone marrow, the latter resulting from the abnormal retention of neutrophils that become senescent 1,2,3,4. Listing a study does not mean it has been evaluated by the u. Jci insight lowlevel cxcr4haploinsufficient hsc engraftment is. It turned out that the woman nih rare disease day 2015 teamwork of scientists and community brings treatments to fruition by lesley earl nci and emily petrus ninds eurordis. A retrospective and prospective natural history study of. To summarize, we have presented a case of sporadic whim syndrome in a young woman whose both sons also turned out to.
More detailed information about the symptoms, causes, and treatments of whim syndrome. Whim syndrome is an acronym for a rare immunodeficiency disorder with. 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. Individuals with whim syndrome are more susceptible to potentially lifethreatening bacterial infections. Mutations in the chemokine receptor gene cxcr4 are. Whim syndrome is an autosomal dominant disorder of warts, hypogammaglobulinemia, infections, and myelokathexis caused by heterozygous gainoffunction mutations in the gene encoding the cxcr4 chemokine receptor kawai and malech, 2009. Beyond whim syndrome, we plan to initiate a phase 1 clinical trial of mavorixafor in another pi, severe congenital neutropenia, or scn, and a phase 12 clinical trial of mavorixafor in waldenstrom macroglobulinemia, or wm, in 2019. Prompt diagnosis and early aggressive treatment of infections is important to reduce long term damage. Clinical and genetic features of warts, hypogammaglobulinemia. Chromothriptic deletions result in functional cure of whim syndrome. Whim syndrome genetic and rare diseases information center.
Karyotype of a woman spontaneously cured of whim syndrome. Oct 31, 2019 rare, intransitive to be seized with a whim. Whim syndrome is a rare congenital immune deficiency, characterized by warts, hypogammaglobulinemia, infections, and myelokathexisthat form the acronym of its name. Leukocyte analysis from whim syndrome patients reveals a. Interim results from a study of a potential treatment for. Whim mining, a capstan or drum with a vertical axle used in mining whim carriage, a type of carriage whim, a reissue of adventures of wim, a book by george cockroft as luke rhinehart. The worlds most comprehensive professionally edited abbreviations and acronyms database all trademarksservice marks referenced on this site are properties of their respective owners. The long term follow up of eight patients highlights the clinical heterogeneity of this disease as well as the main therapeutic. 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 type of primary immunodeficiency where the bodys immune. Plerixafor for the treatment of whim syndrome nejm. Patients with ev usually have a selective defect in cellmediated. Whim syndrome is a rare primary immunodeficiency disorder, which are.
Case studies in immunology available for download and read online in other formats. Stephen whiles, principal environmental health officer at the city council, said the move would make it more convenient for people to reclaim their dogs and would result in more dogs being reunited with their owners. A rare syndrome characterized by warts, hypogammaglobulinemia low blood gammaglobulin levels, recurring bacterial infections and myelokathexis form of neutropenia. The cxcr4 antagonist plerixafor is a potential therapy for myelokathexis, whim syndrome. However, plerixafor is not approved for the treatment of whim syndrome and we are.
Treatment consists on monthly injections of intravenous immunoglobulin, which may reduce the incidence. Murphy, chief of niaids laboratory of molecular immunology, were intrigued and began a quest to unravel this medical mystery. Pathogenesis, diagnosis and therapeutic strategies in whim. 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. Whim syndrome is an acronym for a rare immunodeficiency disorder with each letter representing a predominant feature of the condition. In dictionaries, though, it does have mention of at whim, on whim, on the whim of, but they dont say if they have any difference in meaning, or if at all they have any. 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. Ways to give make a one time or monthly gift donate via paypal link above or send a check to whim whim at 3417 evanston ave.
A prominent and unexplained feature of whim is myelokathexis hypercellularity with apoptosis of mature myeloid cells in bone marrow and. For example, as rare as whim syndrome an acronym for warts, hypogammaglobulinemia, infections, and myelokathexis may be, it is perhaps no less likely than mds as an explanation for an isolated neutropenia. Twin to twin transfusion syndrome vici syndrome whim syndrome wiskott aldrich syndrome woods black norbury syndrome. X4 pharmaceuticals to merge with arsanis in stock for stock transaction combined company will operate as x4 pharmaceuticals, inc. None of these measures has been formally evaluated for efficacy in whim syndrome whims. Consistent with nemours familycentered approach, the treatment team provides a thorough evaluation and speci. A defect in cxcr4 s ignaling diaz and gulino 351 and premalignant dy splastic changes, necessitating surgi cal resection of inv olved tissue 6,1 0.
Whim syndrome myelokathexis reproduced in the nodscid. The truncation of the receptor protein results in the inability of downregulation after stimulation. A report of whim syndrome myelokathexis clinical features and. They combine the advantages of smallmolecule drugs and antibodybased. Whim syndrome in the first half of 2019, said paula ragan, phd, president and chief executive officer of x4 pharmaceuticals. Based on the patient described in this article, whim 09, and subsequent mechanistic. Clinical data from a phase 2 study of the experimental drug x4p001rd for the treatment of whim syndrome has been announced at the european hematology associations 23 rd congress in stockholm. Whim syndrome is a rare primary immunodeficiency disorder, which are disorders in which the bodys immune system does not function properly. Summary whim syndrome warts, hypogammaglobulinemia, infections, and myelokathexis, a primary immunodeficiency disorder involving.
In reverse merger with arsanis, x4 pharmaceuticals will. Cerebellar involvement in warts hypogammaglobulinemia. She said that she and two of her three daughters, ages 21 and 23, wanted to be evaluated for whim syndrome. 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. A highquality core biopsy specimen of adequate size is also important to rule out the possibility of a sampling bias, in which the. Whim syndrome is a type of primary immunodeficiency disorder, which means that it is associated with the immune system not functioning. Name abbreviation country or countries where used icd10 version used description number of. Treatment may include injection of granulocyte colony. Russias perpetual geopolitics mayjune 2016 3 decade, russian president vladimir putin has returned to the trend of relying on the state to manage the gulf between russia and the more powerful west. Whim syndrome warts, hypogammaglobulinemia, infections, and myelokathexis, a primary immunodeficiency disorder involving panleukopenia, is caused by. X4s lead candidate x4p001 is a small molecule that inhibits the binding of chemokine cxcl12 to cxc receptor type 4 cxcr4, and is set to enter phase iii trials next year for the treatment of warts, hypogammaglobulinemia, immunodeficiency, and myelokathexis whim syndrome. Treatment of whim patients currently consists of symptom relief, leading to. The study of inherited immunodeficiencies has proven valuable in elucidating molecular signaling cascades underlying the developmental and functional regulation of the human immune system. At the closing of the merger, we issued shares of our common stock to x4.