DOCK8 immunodeficiency syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

DOCK8 immunodeficiency syndrome is a disorder of the immune system. The condition is characterized by recurrent infections that are severe and can be life-threatening. The infections can be caused by bacteria, viruses, or fungi. Skin infections cause rashes, blisters, accumulations of pus (abscesses), open sores, and scaling. People with DOCK8 immunodeficiency syndrome also tend to have frequent bouts of pneumonia and other respiratory tract infections. Other immune system-related problems in people with DOCK8 immunodeficiency syndrome include an inflammatory skin disorder called eczema, food or environmental allergies, and asthma.

DOCK8 immunodeficiency syndrome is characterized by abnormally high levels of an immune system protein called immunoglobulin E (IgE) in the blood; the levels can be more than 10 times higher than normal for no known reason. IgE normally triggers an immune response against foreign invaders in the body, particularly parasitic worms, and plays a role in allergies. It is unclear why people with DOCK8 immunodeficiency syndrome have such high levels of this protein. People with DOCK8 immunodeficiency syndrome also have highly elevated numbers of certain white blood cells called eosinophils (hypereosinophilia). Eosinophils aid in the immune response and are involved in allergic reactions.

Some people with DOCK8 immunodeficiency syndrome have neurological problems, such as paralysis that affects the face or one side of the body (hemiplegia). Blockage of blood flow in the brain or abnormal bleeding in the brain, both of which can lead to stroke, can also occur in DOCK8 immunodeficiency syndrome.

People with DOCK8 immunodeficiency syndrome have a greater-than-average risk of developing cancer, particularly cancers of the blood or skin.

DOCK8 immunodeficiency syndrome is also commonly called autosomal recessive hyper-IgE syndrome. However, researchers have identified several conditions that feature elevated levels of IgE and that follow an autosomal recessive pattern of inheritance. Each of these conditions has its own set of additional signs and symptoms and a different genetic cause. Some doctors consider these conditions forms of hyper-IgE syndrome, while others consider them independent disorders.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

DOCK8 immunodeficiency syndrome is caused by mutations in the DOCK8 gene. The protein produced from this gene plays a critical role in the survival and function of several types of immune system cells. One of the functions of the DOCK8 protein is to help maintain the structure and integrity of immune cells called T cells and NK cells, which recognize and attack foreign invaders, particularly as these cells travel to sites of infection within the body. In addition, the DOCK8 protein is involved in chemical signaling pathways that stimulate other immune cells called B cells to mature and produce antibodies, which are specialized proteins that attach to foreign particles and germs, marking them for destruction.

DOCK8 gene mutations result in the production of little or no functional DOCK8 protein. Shortage of this protein impairs normal immune cell development and function. It is thought that T cells and NK cells lacking DOCK8 protein are abnormal and die too easily, particularly when moving through the layers of skin. A shortage of these immune cells impairs the immune response to foreign invaders, accounting for the severe skin infections common in DOCK8 immunodeficiency syndrome. A lack of DOCK8 protein also impairs B cell maturation and the production of antibodies. Impairment of this type of immune response leads to recurrent respiratory tract infections in people with this disorder. It is unclear how DOCK8 gene mutations are involved in other features of DOCK8 immunodeficiency syndrome, such as the elevation of IgE levels, and neurological problems.

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

DOCK8 immunodeficiency syndrome is a rare disorder whose prevalence 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.

Asthma · Very frequent (99-80%)

Asthma is characterized by increased responsiveness of the tracheobronchial tree to multiple stimuli, leading to narrowing of the air passages with resultant dyspnea, cough, and wheezing.

Atopic dermatitis · Very frequent (99-80%)

Atopic dermatitis (AD) or atopic eczema is an itchy, inflammatory skin condition with a predilection for the skin flexures. It is characterized by poorly defined erythema with edema, vesicles, and weeping in the acute stage and skin thickening (lichenification) in the chronic stage.

Chronic otitis media · Very frequent (99-80%)

Chronic otitis media refers to fluid, swelling, or infection of the middle ear that does not heal and may cause permanent damage to the ear.

Decreased total B cell count · Very frequent (99-80%)

The absolute number of B cells in the blood, per microlitre is below the lower limit of normal of the reference range for the appropriate sex and age-group.

Decreased total T cell count · Very frequent (99-80%)

Abnormal decrease in the absolute number of T cells, commonly characterized as CD3+ lymphocytes, per microliter of blood, compared to a reference range for a given sex and age-group. These may include both TCR alpha/beta and gamma/delta T cells.

Increased circulating IgE concentration · Very frequent (99-80%)

An abnormally increased overall level of immunoglobulin E in blood.

Onychomycosis · Very frequent (99-80%)

Increased susceptibility to fungal infection of the nail apparatus (onychomycosis), as manifested by recurrent or severe infection of the nail plate, nail bed, or nail matrix caused by fungal organisms. Causative agents include dermatophytes (Trichophyton species) and Candida species.

Pneumonia · Very frequent (99-80%)

Inflammation of any part of the lung parenchyma.

Other findings in the same source

From: Orphanet

Additional reported features include Recurrent bacterial skin infections (Very frequent (99-80%)); Recurrent candida infections (Very frequent (99-80%)); Recurrent respiratory infections (Very frequent (99-80%)); Recurrent sinusitis (Very frequent (99-80%)); Recurrent viral infections (Very frequent (99-80%)); Skin ulcer (Very frequent (99-80%)); Verrucae (Very frequent (99-80%)); Squamous cell carcinoma (Occasional (29-5%)); Squamous cell carcinoma of the vulva (Occasional (29-5%)); Anal canal squamous carcinoma (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing DOCK8 immunodeficiency 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

The material gathered for this draft does not provide a complete condition-specific treatment pathway for DOCK8 immunodeficiency syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

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.