Rare Endocrinology News

Disease Profile

WHIM syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Childhood

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ICD-10

D81.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Warts, Hypogammaglobulinemia, Infections, and Myelokathexis; WHIMS

Categories

Congenital and Genetic Diseases; Immune System Diseases

Summary

WHIM syndrome is an acronym for a rare immunodeficiency disorder with each letter representing a predominant feature of the condition: (W) = warts; (H) = hypogammaglobulinemia; (I) = infections; and (M) = myelokathexis (retention of neutrophils in the bone marrow). Symptoms usually begin in early childhood with recurrent bacterial infections such as respiratory infections and cellulitis. In later childhood, individuals develop widespread warts that often become persistent despite treatments that are normally effective. Warts that involve the genital area may eventually cause cancer. It is caused by mutations in the CXCR4 gene and is inherited in an autosomal dominant manner. Treatment may include medications that replace antibodies (intravenous immunoglobulin) or increase the number of neutrophils; vaccinations; and prophylactic antibiotics to reduce the risk of infections.[1][2]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of neutrophil morphology
0011992
Bone marrow hypercellularity
0031020
Lymphopenia
Decreased blood lymphocyte number
Low lymphocyte number

[ more ]

0001888
Myelokathexis
0031160
Neutropenia
Low blood neutrophil count
Low neutrophil count

[ more ]

0001875
30%-79% of people have these symptoms
Decreased circulating antibody level
0004313
Recurrent bacterial infections
Bacterial infections, recurrent
Frequent bacterial infections
Increased susceptibility to bacterial infections
Recurrent major bacterial infections

[ more ]

0002718
Recurrent pneumonia
0006532
Recurrent upper respiratory tract infections
Recurrent colds
0002788
Verrucae
Warts
0200043
5%-29% of people have these symptoms
Abnormality of the small intestine
0002244
Bronchiectasis
Permanent enlargement of the airways of the lungs
0002110
Cervix cancer
0030079
Limb ataxia
0002070
Neurological speech impairment
Speech disorder
Speech impairment
Speech impediment

[ more ]

0002167
Otitis media
Middle ear infection
0000388
Pharyngitis
0025439
Poor fine motor coordination
0007010
Postural instability
Balance impairment
0002172
Sinusitis
Sinus inflammation
0000246
Tetralogy of Fallot
0001636
1%-4% of people have these symptoms
Atelectasis
Partial or complete collapse of part or entire lung
0100750
Cellulitis
Bacterial infection of skin
Skin infection

[ more ]

0100658
Cutaneous melanoma
0012056
Lymphadenitis
Inflammation of the lymph nodes
0002840
Meningitis
0001287
Parotitis
0011850
Seizure
0001250
Sepsis
Infection in blood stream
0100806
Severe periodontitis
0000166
Vitiligo
Blotchy loss of skin color
0001045
Percent of people who have these symptoms is not available through HPO
Abnormal morphology of female internal genitalia
0000008
Abnormality of bone marrow cell morphology
0005561
Abnormality of female external genitalia
Abnormal female external genitalia
0000055
Autosomal dominant inheritance
0000006
Decreased circulating IgG level
0004315
Infantile onset
Onset in first year of life
Onset in infancy

[ more ]

0003593

Treatment

Early diagnosis and aggressive medical management are very important for individuals with WHIM syndrome. Treatment of the condition currently includes G-CSF (a medication that stimulates the production of neutrophils); intravenous immunoglobulins (IVIG) for hypogammaglobulinemia; prophylactic antibiotics to prevent infection; and aggressive surveillance for, and treatment of, skin and mucosal HPV-related lesions. The dose of G-CSF should be determined for each individual, and adjustments may be needed periodically. IVIG has been shown to be effective at decreasing risk of infections, and it has also been reported that the hypogammaglobulinemia may improve following treatment with G-CSF. The use of prophylactic antibiotics in individuals affected with WHIM has not been specifically studied, but the benefits have been assumed based on studies on other types of immunodeficiency disorders. Infections should be diagnosed and treated as soon as possible.[3]

A new study sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) found that a drug called plerixafor, already approved by the Food and Drug Administration for use in patients undergoing a bone marrow transplant, may also have promise for treating people who have WHIM syndrome. Plerixafor blocks the activity of CXCR4 (which is increased in affected individuals) and may become a targeted therapy for WHIM syndrome. To read more about this ongoing study, click here.

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Social Networking Websites

    • RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

      Organizations Providing General Support

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        In-Depth Information

        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss WHIM syndrome. Click on the link to view a sample search on this topic.

          Selected Full-Text Journal Articles

          • Hagan JB, Nguyen PL. WHIM Syndrome. Mayo Clin Proc. September 2007;82(9):1031.
          • The Orphanet Journal of Rare Diseases has published an article with information on this condition. This journal is affiliated with the Orphanet reference portal for information on rare diseases and orphan drugs.

            References

            1. DH McDermott, M.D., National Institutes of Allergy and Infectious Diseases, personal communication, August 2009 .
            2. George Diaz, Virginia Gulino. Whim syndrome. Orphanet Encyclopedia. June 2004; https://www.orpha.net/data/patho/GB/uk-Whim.pdf. Accessed 11/13/2011.
            3. Kawai, Toshinaoa; Malech, Harry L. WHIM syndrome: congenital immune deficiency disease. Current Opinion in Hematology. January 2009; 16(1):20-26.

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