What are the other Names for this Condition? (Also known as/Synonyms)

• NDAS (NEMO Deleted Autoinflammatory Syndrome)
• NEMO Deleted Autoinflammatory Syndrome (NDAS)
• NEMO/NDAS (NEMO Deleted Autoinflammatory Syndrome)

What is NEMO Deleted Exon 5 Autoinflammatory Syndrome? (Definition/Background Information)

• NEMO Deleted Exon 5 Autoinflammatory Syndrome (NEMO/NDAS) is a rare genetic disorder characterized by recurrent inflammation episodes in various body parts. A genetic mutation in the NEMO gene causes NEMO/NDAS
• This gene provides instructions for making a protein critical in regulating the immune system. A deletion in a portion of this gene leads to dysfunction of the NEMO protein, leading to the development of this autoinflammatory disorder
• NEMO Deleted Exon 5 Autoinflammatory Syndrome is inherited in an X-linked recessive pattern and is almost only seen in males. The primary risk factor is having a family history of the disorder
• The signs and symptoms of NEMO Deleted Exon 5 Autoinflammatory Syndrome can vary widely and may include recurrent fever, skin rashes, joint pain and stiffness, swelling of the lymph nodes, fatigue, abdominal pain, and diarrhea
• The diagnosis of NEMO Deleted Exon 5 Autoinflammatory Syndrome is made based on clinical symptoms, family history, and genetic testing. Genetic testing can confirm the presence of a mutation in the NEMO gene
• The treatment of NEMO Deleted Exon 5 Autoinflammatory Syndrome involves using non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids to reduce inflammation. In more severe cases, other immunosuppressive drugs may be used to control symptoms
• As NEMO Deleted Exon 5 Autoinflammatory Syndrome is a genetic disorder, it cannot be prevented. However, early diagnosis and treatment can help to manage symptoms and prevent complications
• The prognosis of NEMO Deleted Exon 5 Autoinflammatory Syndrome can vary widely depending on the severity of symptoms and treatment effectiveness. With appropriate management, many individuals can lead relatively normal lives. Without suitable treatment, complications such as chronic joint pain and disability, infertility, and kidney failure can develop

Who gets NEMO Deleted Exon 5 Autoinflammatory Syndrome? (Age and Sex Distribution)

• NEMO Deleted Exon 5 Autoinflammatory Syndrome is a rare disorder that affects males almost exclusively
• Worldwide, no racial or ethnic group preference is noted

What are the Risk Factors for NEMO Deleted Exon 5 Autoinflammatory Syndrome? (Predisposing Factors)

• The primary risk factor for NEMO Deleted Exon 5 Autoinflammatory Syndrome is having a family history of the disorder
• NEMO/NDAS is almost exclusively seen in males, as it is an X-linked disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of NEMO Deleted Exon 5 Autoinflammatory Syndrome? (Etiology)

The cause of NEMO Deleted Exon 5 Autoinflammatory Syndrome is a genetic mutation in the NEMO gene, also known as the IKBKG gene (it is sometimes portrayed as the IKBKG/NEMO gene). The NEMO gene is on the X chromosome. In other words, NEMO/NDAS is an X-linked IKGKB/NEMO germline mutation.

• This gene provides instructions for making a protein called Nuclear factor-kappa B Essential MOdulator (NEMO), which is critical in regulating the immune system
• A deletion in exon 5 of this gene leads to dysfunction of the NEMO protein, leading to the development of autoinflammatory disorder or immunodeficiency
• The condition is inherited in an X-linked recessive pattern, meaning an individual must inherit one copy of the mutated NEMO gene from their mother to develop the disorder. Since it is X-linked, the disorder is primarily observed in males

A few cases seem to have a differing inheritance pattern.

What are the Signs and Symptoms of NEMO Deleted Exon 5 Autoinflammatory Syndrome?

The signs and symptoms of NEMO Deleted Exon 5 Autoinflammatory Syndrome (NEMO/NDAS) can vary widely. There are two pathways that the gene mutation can lead to. One outcome is the autoinflammatory disorder, which shows many infection-like signs and symptoms without any actual infectious agent. This is the pattern of typical NEMO/NDAS:

• Recurrent fevers
• Nodular skin rashes
• Uveitis (inflammation of the front interior portions of the eye)
• Chorioretinitis and optic neuritis (inflammation of the posterior eye/optic nerve)
• Panniculitis (fat inflammation)
• Hepatitis (liver inflammation without infection)
• An absence of severe infections

The pattern of those with frequent severe infections:

• Inability to protect against pyogenic (pus-forming) bacteria such as Pneumococcus and Staphylococcus, sometimes mycobacteria and fungi
• Most organs can be affected, but the most common ones are the skin, upper and lower respiratory tract, urinary (bladder and kidneys) tract, and central nervous system
• In the absence of infection, autoinflammatory symptoms are also common

How is NEMO Deleted Exon 5 Autoinflammatory Syndrome Diagnosed?

The diagnosis of NEMO Deleted Exon 5 Autoinflammatory Syndrome is typically made based on the following:

• Physical examination and evaluation of clinical symptoms
• Family history assessment
• Eye examination
• Blood tests for antibody levels, inflammatory marker levels, and others
• Genetic testing for mutations in the NEMO gene

Other testing will be necessary to diagnose and treat incontinentia pigmenti (IP) or anhidrotic ectodermal dysplasia if they are associated with NEMO syndrome.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of NEMO Deleted Exon 5 Autoinflammatory Syndrome?

Complications of NEMO Deleted Exon 5 Autoinflammatory Syndrome can include:

• Eye inflammation with visual loss
• Scarring of the subcutaneous fat
• Multiple infections
• Consequences of chronic severe inflammation

How is NEMO Deleted Exon 5 Autoinflammatory Syndrome Treated?

The treatment of NEMO Deleted Exon 5 Autoinflammatory Syndrome (NEMO/NDAS) typically involves the following:

• Use of non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids to reduce inflammation
• In more severe cases, other immunosuppressive drugs may be used to control symptoms

First reported only a few years ago, treatment protocols have not yet been established for NEMO/NDAS.

How can NEMO Deleted Exon 5 Autoinflammatory Syndrome be Prevented?

NEMO Deleted Exon 5 Autoinflammatory Syndrome is a genetic disorder that cannot be prevented.

• However, early diagnosis and treatment can help to manage symptoms and prevent complications
• Genetic counseling and testing may be recommended for individuals with a family history of the disorder and for couples planning to have children

What is the Prognosis of NEMO Deleted Exon 5 Autoinflammatory Syndrome? (Outcomes/Resolutions)

• The prognosis for individuals with NEMO Deleted Exon 5 Autoinflammatory Syndrome can vary widely depending on the severity of symptoms and the effectiveness of treatment.
• With few cases reported, reliable prognostic information is presently unavailable

Additional and Relevant Useful Information for NEMO Deleted Exon 5 Autoinflammatory Syndrome:

The NEMO gene is also abnormal in two other distinctive syndromes. One is Anhidrotic Ectodermal Dysplasia with Immunodeficiency (EDA-ID). This presents at birth with thickened dry skin and sparse hair, with teeth developing with a conical shape. The immunodeficiency leads to frequent Staphylococcus and Pneumococcus infections. Almost all these patients are male. These patients also develop the skin and intestinal inflammation seen in NEMO/NDAS.

The other severe multiorgan disease linked with NEMO gene malformations is Incontinentia pigmenti (IP). Incontinentia pigmenti patients do not develop immunodeficiency or the skin and intestinal inflammation of NEMO/NDAS. Incontinentia pigmenti patients have pigmented and warty skin lesions, eye malformations, and cardiac malformations.

The above article only deals with NEMO Deleted Exon 5 Autoinflammatory Syndrome that is not linked to Anhidrotic Ectodermal Dysplasia with Immunodeficiency (EDA-ID) or Incontinentia Pigmenti (IP). It is a stand-alone autoinflammatory syndrome without organ malformations.