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Disease Profile

Omenn 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

Infancy

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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.

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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)

Reticuloendotheliosis familial with eosinophilia; Severe combined immunodeficiency with hypereosinophilia

Categories

Congenital and Genetic Diseases; Immune System Diseases

Summary

Omenn syndrome is an autosomal recessive form of severe combined immunodeficiency (SCID) characterized by erythroderma (skin redness), desquamation (peeling skin), alopecia (hair loss), chronic diarrhea, failure to thrive, lymphadenopathy (enlarged lymph nodes), eosinophilia, hepatosplenomegaly, and elevated serum IgE levels.[1][2][3] Patients are highly susceptible to infection and develop fungal, bacterial, and viral infections typical of SCID. In this syndrome, the SCID is associated with low IgG, IgA, and IgM and the virtual absence of B cells. There is an elevated number of T cells, but their function is impaired.[1] Omenn syndrome has been found to be caused by mutations in the RAG1 or RAG2 genes.[1][3] Additional causative genes have been identified.[1] Early recognition of this condition is important for genetic counseling and early treatment. If left untreated, Omenn syndrome is fatal. The prognosis may be improved with early diagnosis and treatment with compatible bone marrow or cord blood stem cell transplantation.[1][2]

Symptoms

Infants with Omenn syndrome typically present shortly after birth, usually by 3 months of age. This is similar to other types of severe combined immunodeficiency (SCID). The characteristic skin findings (red and peeling skin), chronic diarrhea, and failure to thrive often precede the onset of infections. Life-threatening infections caused by common viral, bacterial, and fungal pathogens occur next. Lymphadenopathy and hepatosplenomegaly, both symptoms unique to Omenn syndrome, develop next.[1]

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
Abnormal lymphocyte morphology
0004332
Alopecia
Hair loss
0001596
Chronic diarrhea
0002028
Erythroderma
0001019
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Hepatomegaly
Enlarged liver
0002240
Lymphadenopathy
Swollen lymph nodes
0002716
Severe combined immunodeficiency
0004430
30%-79% of people have these symptoms
Aplasia/Hypoplasia of the eyebrow
Absence of eyebrow
Lack of eyebrow
Missing eyebrow

[ more ]

0100840
Desquamation of skin soon after birth
0007549
Dry skin
0000958
Edema
Fluid retention
Water retention

[ more ]

0000969
Eosinophilia
High blood eosinophil count
0001880
Fever
0001945
Pneumonia
0002090
Pruritus
Itching
Itchy skin
Skin itching

[ more ]

0000989
Splenomegaly
Increased spleen size
0001744
Thickened skin
Thick skin
0001072
5%-29% of people have these symptoms
Abnormality of the metaphysis
Abnormality of the wide portion of a long bone
0000944
Anemia
Low number of red blood cells or hemoglobin
0001903
Autoimmunity
Autoimmune disease
Autoimmune disorder

[ more ]

0002960
Hypothyroidism
Underactive thyroid
0000821
Lymphoma
Cancer of lymphatic system
0002665
Nephrotic syndrome
0000100
Sepsis
Infection in blood stream
0100806
Short toe
Short toes
Stubby toes

[ more ]

0001831
Thyroiditis
Thyroid gland inflammation
0100646
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Diarrhea
Watery stool
0002014
Hypoplasia of the thymus
Small thymus
0000778
Hypoproteinemia
Decreased protein levels in blood
0003075
Recurrent bacterial infections
Bacterial infections, recurrent
Frequent bacterial infections
Increased susceptibility to bacterial infections
Recurrent major bacterial infections

[ more ]

0002718
Recurrent fungal infections
0002841
Recurrent viral infections
0004429
Severe B lymphocytopenia
0005365
Thrombocytopenia
Low platelet count
0001873

Cause

Omenn syndrome is a genetically heterogeneous condition (meaning that it may be caused by a number of different genes). While most cases are attributed to mutations in the RAG genes (RAG-1 and RAG2 genes have been mapped to chromosome band 11p13), recent reports describe Omenn syndrome in the absence of RAG mutations.[1][3] Omenn syndrome caused by mutations in ARTEMIS, ADA, ILRA2, ILRA7, CHD7, and DNA ligase 4 have been described in the medical literature. Some cases of Omenn syndrome have also been found in association with 22q11 microdeletion syndrome.[1]

Treatment

The standard treatment for Omenn syndrome is bone marrow transplantation or cord blood stem cell transplantation.[1][2] General care for any patient with severe combined immunodeficiency (SCID), including Omenn syndrome, includes isolation to prevent infection and meticulous skin and mucosal hygienic practices while the patient is awaiting stem cell reconstitution. Broad-spectrum antibiotics may be administered parenterally while cultures and body fluid analyses are in progress. Parenteral nutrition may also be provided as therapy for diarrhea and failure to thrive.[1] A detailed description of therapeutic options is provided in the referenced eMedicine article.

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

    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.

    Where to Start

      In-Depth Information

      • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
      • 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 Omenn syndrome. Click on the link to view a sample search on this topic.

        References

        1. Schwartz RA, Lin RY. Omenn Syndrome. eMedicine. May 9, 2011; https://emedicine.medscape.com/article/887687-overview. Accessed 3/21/2012.
        2. Aleman K, Noordzij JG, de Groot R, van Dongen JJ, Hartwig NG. Reviewing Omenn syndrome. Eur J Pediatr. 2001; https://www.ncbi.nlm.nih.gov/pubmed/11795679. Accessed 3/21/2012.
        3. Zhang ZY, Ahao XD, Jiang LP, Liu EM, Cui YX, Wang M, Wei H, Yu J, An YF, Yang XQ. Clinical characteristics and molecular analysis of three Chinese children with Omenn syndrome. Pediatr Allergy Immunol. 2011; https://www.ncbi.nlm.nih.gov/pubmed/21771083. Accessed 3/21/2012.

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