Omenn syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

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.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

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.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

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.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

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.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal lymphocyte morphology · Very frequent (99-80%)

An abnormality of lymphocytes.

Alopecia · Very frequent (99-80%)

A noncongenital process of hair loss, which may progress to partial or complete baldness.

Chronic diarrhea · Very frequent (99-80%)

The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks.

Erythroderma · Very frequent (99-80%)

An inflammatory exfoliative dermatosis involving nearly all of the surface of the skin. Erythroderma develops suddenly. A patchy erythema may generalize and spread to affect most of the skin. Scaling may appear in 2-6 days and be accompanied by hot, red, dry skin, malaise, and fever.

Failure to thrive · Very frequent (99-80%)

Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.

Hepatomegaly · Very frequent (99-80%)

Abnormally increased size of the liver.

Lymphadenopathy · Very frequent (99-80%)

Enlargement (swelling) of a lymph node.

Severe combined immunodeficiency · Very frequent (99-80%)

A type of primary immune deficiency that is characterized by a more severe defect in both the T- and B-lymphocyte systems.

Other findings in the same source

From: Orphanet

Additional reported features include Aplasia/Hypoplasia of the eyebrow (Frequent (79-30%)); Dry skin (Frequent (79-30%)); Edema (Frequent (79-30%)); Fever (Frequent (79-30%)); Increased total eosinophil count (Frequent (79-30%)); Increased total leukocyte count (Frequent (79-30%)); Pneumonia (Frequent (79-30%)); Pruritus (Frequent (79-30%)); Splenomegaly (Frequent (79-30%)); Thickened skin (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Omenn syndrome is Allergy and Immunology, with a allergist / clinical immunologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the history suggest an allergy, an immune problem or another explanation?
• How would any proposed allergy or immune test change care?
• Is an individual emergency plan needed, and who should understand it?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.