Omenn Syndrome

Omenn syndrome is an inherited disorder of the immune system (immunodeficiency). Omenn syndrome is one of several forms of severe combined immunodeficiency (SCID), a group of disorders that cause individuals to have virtually no immune protection from bacteria, viruses, and fungi. Individuals with SCID are prone to repeated and persistent infections that can be very serious or life-threatening. Infants with Omenn syndrome typically experience pneumonia and chronic diarrhea. Often the organisms that cause infection in people with this disorder are described as opportunistic because they ordinarily do not cause illness in healthy people.

In addition to immunodeficiency, children with Omenn syndrome develop autoimmunity, in which the immune system attacks the body's own tissues and organs. This abnormal immune reaction can cause very red skin (erythroderma), hair loss (alopecia), and an enlarged liver and spleen (hepatosplenomegaly). In addition, affected individuals have enlargement of tissues that produce infection-fighting white blood cells called lymphocytes. These include the thymus, which is a gland located behind the breastbone, and lymph nodes, which are found throughout the body.

If not treated in a way that restores immune function, children with Omenn syndrome usually survive only until age 1 or 2.

Frequency

Overall, the various forms of SCID are estimated to affect 1 in 75,000 to 100,000 newborns. The exact prevalence of Omenn syndrome is unknown.

Causes

Mutations in several genes involved in immune system function can cause Omenn syndrome. The two most frequent causes are mutations in the RAG1 and RAG2 genes. These genes provide instructions for making proteins that are active in two types of lymphocytes called B cells and T cells. To help fight infections, B cells and T cells have special proteins on their surface that help them recognize foreign invaders; these proteins must be somewhat different from each other to be able to recognize a wide variety of substances. The RAG1 and RAG2 proteins help increase the diversity of proteins that are on the surface of these cells.

RAG1 and RAG2 gene mutations that cause Omenn syndrome drastically reduce the respective protein's function. As a result, the diversity of proteins on the surface of B cells and T cells is severely limited, impairing the cells' ability to recognize foreign invaders and fight infections. The abnormal B cells and T cells result in the frequent, life-threatening infections of Omenn syndrome. The decrease in lymphocyte function leads to a reduction in the numbers of B cells. The number of T cells is typically normal, although they are highly similar because they are derived from just a few functional precursor cells. The abnormal T cells attack the body's own cells and tissues, accounting for the autoimmune features of Omenn syndrome.

Learn more about the genes associated with Omenn syndrome

• CARD11
• IL7R
• RAG1
• RAG2

Additional Information from NCBI Gene:

• DCLRE1C
• LIG4

Inheritance Pattern

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.