Omenn Syndrome Clinical Presentation

Updated: Mar 01, 2017
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Harumi Jyonouchi, MD  more...
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Presentation

History

In the first weeks after birth, infants with Omenn syndrome present with erythrodermia and diarrhea. The severity of the dermatitis is associated with episodes of S aureus sepsis; diarrhea predisposes patients to gram-negative enteric bacterial sepsis.

As in other forms of severe combined immunodeficiency (SCID), life-threatening infections with common viral, bacterial, and fungal pathogens occur next.

Chronic diarrhea and infection lead to failure to thrive, which is also characteristic of any other type of SCID.

Lymphadenopathy and hepatosplenomegaly soon develop; however, these are unusual in other types of SCID unless maternal engraftment or transfusion-associated graft versus host disease (GVHD) occurs.

P carinii pneumonia and poliomyelitis due to the attenuated oral poliovirus are classic infections in Omenn syndrome and in other types of SCID.

A child with Omenn syndrome and the rare bone marrow disorder of reticular dysgenesis has been described. [13]

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Physical

Patients present in the first weeks of life with a unique generalized dermatitis that may be mistaken for eczema. However, the dermatitis has a pachydermatis appearance that progresses to desquamation (see the image below). Protein loss via the skin and gut may result in generalized edema.

A unique dermatitis characterizes Omenn syndrome. A unique dermatitis characterizes Omenn syndrome. The dermatitis initially resembles eczema, but with a pachydermia, as observed here. The lesions progress to desquamation. Failure to thrive is evident. This infant weighed 6 pounds at age 6 months; his weight had not changed since birth.

Lymphadenopathy distinguishes Omenn syndrome from most other SCID variants.

Hepatosplenomegaly is also usually present.

Failure to thrive associated with chronic diarrhea and dermatitis should always raise the suspicion of SCID.

Alopecia is another frequent finding.

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Causes

When mutations in the recombinase genes RAG-1 and RAG-2 have been sought, homozygous and heterozygous mutations have been found. In contrast to T- B- NKC+ SCID in which RAG-1 and RAG-2 mutations affect the active core of the gene, homozygous mutations affecting the active core have not been observed in Omenn syndrome. Approximately half of the mutations are missense mutations, and the remainder are nonsense, deletion, frameshift, duplication, and splice mutations. RAG-1 and RAG-2 genes have been mapped to chromosome band 11p13.

Although most cases of Omenn syndrome are due to mutations in the RAG genes, recent reports describe Omenn syndrome in the absence of RAG mutations. Omenn syndrome caused by mutations in ARTEMIS, ADA, ILRA2, ILRA7, CHD7, and DNA ligase 4 has been described. Omenn syndrome caused by 22q11 microdeletion syndrome has also been described. Therefore, Omenn syndrome is now defined as a genetically heterogeneous condition in which patients with similar phenotypes may have unidentified genetic defects.

Various mutations are associated with the Omenn phenotype characterized by skin erythroderma, oligoclonal-activated T cells and elevated IgE in the absence of circulating B cells. [4] Omenn syndrome is usually due to hypomorphic defects in genes involved in V(D)J recombination, mainly RAG genes, whereas Omenn-like features are linked with mutations in genes involved in the maturation steps of lymphoid cells other than V(D)J recombination.

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