DOCK8 deficiency
DOCK8 deficiency, also called DOCK8 immunodeficiency syndrome, is the autosomal recessive form of hyperimmunoglobulin E syndrome, a genetic disorder characterized by elevated immunoglobulin E levels, eosinophilia, and recurrent infections with staphylococcus and viruses. It is caused by a mutation in the "DOCK8" gene. Signs and symptoms. The signs and symptoms of DOCK8 deficiency are similar to the autosomal dominant form, STAT3 deficiency. However, in DOCK8 deficiency, there is no skeletal or connective tissue involvement, and affected individuals do not have the characteristic facial features of those with autosomal dominant hyper-IgE syndrome. DOCK8 deficient children often have eczema , respiratory and skin staphylococcus infections. Beyond these, many other recurrent infections have been observed, including recurrent fungal infections and recurrent viral infections (including molluscum contagiosum, herpes simplex, and herpes zoster), recurrent upper respiratory infection (including "Streptococcus pneumoniae", "Haemophilus influenzae", respiratory syncytial virus, and adenovirus), recurrent sinusitis, recurrent otitis media, mastoiditis, pneumonia, bronchitis with bronchiectasis, osteomyelitis, candidiasis, meningitis (caused by cryptococcus or H. influenzae), pericarditis, salmonella enteritis, and giardiasis. Other dermatologic problems include squamous-cell carcinoma/dysplasia (vulvar, anal, and facial). Immune problems are also common, including autoimmune hemolytic anemia, severe allergies (both food and environmental), asthma, and reactive airway disease . The nervous system may also be affected; observed conditions in DOCK8 deficient people include hemiplegia, ischemic stroke, subarachnoid hemorrhage, and facial paralysis. Vascular complications are common, including aortic aneurysm, cerebral aneurysm, vessel occlusion and underperfusion, and leukocytoclastic vasculitis. Pathophysiology. DOCK8, or "dedicator of cytokinesis 8", is a protein involved in regulating the actin skeleton of the cell. It may also be a tumor suppressor, since DOCK8 is lost in many cancers and people with DOCK8 deficiency are prone to developing malignancies. When it is mutated, an incorrect protein is produced, so there is, at most, a trace level of functional  DOCK8 protein in the cell. There are a variety of loss-of-function mutations in DOCK8 that can cause deficiency and hyperimmunoglobulin E, including frameshift mutations, nonsense mutations, microdeletions, and, most commonly, large deletions. The low number of T cells (T cell lymphopenia) and other lymphocytes appears to be responsible for the susceptibility to infections, and the poor humoral immunity is responsible for low response to vaccines. However, how DOCK8 is involved in the loss of T cells is not known. Diagnosis. A diagnosis can only be definitively made after genetic testing to look for a mutation in the "DOCK8