Current Status of Dedicator of Cytokinesis-Associated Immunodeficiency: DOCK8 and DOCK2

Abstract

DOCK8 deficiency is an autosomal recessive combined immunodeficiency disease associated with elevated IgE, atopy, recurrent sinopulmonary and cutaneous viral infections, and malignancy. The DOCK8 protein is critical for cytoskeletal organization, and deficiency impairs dendritic cell transmigration, T-cell survival, and NK cell cytotoxicity. Early hematopoietic stem cell transplantation is gaining prominence as a definitive treatment given the potential for severe complications and mortality in this disease. Recently, DOCK2 deficiency has been identified in several patients with early-onset invasive bacterial and viral infections.

Keywords: Atopic dermatitis; Cutaneous viral infection; Dedicator of cytokinesis 2; Dedicator of cytokinesis 8; Immunodeficiency; Malignancy.

Fig. 1

Fig. 1a, 1b: Chronic severe eczematous dermatitis in a 6 year old male with DOCK8 deficiency.

Fig. 1

Fig. 1a, 1b: Chronic severe eczematous dermatitis in a 6 year old male with DOCK8 deficiency.

Fig. 2

Fig. 2a, 2b: Large, widespread warts as a manifestation of severe human papilloma virus infection in a 15 year old female with DOCK8 deficiency. Fig. 2c: Extensive molluscum contagiosum in a patient with DOCK8 deficiency.

Fig. 2

Fig. 2a, 2b: Large, widespread warts as a manifestation of severe human papilloma virus infection in a 15 year old female with DOCK8 deficiency. Fig. 2c: Extensive molluscum contagiosum in a patient with DOCK8 deficiency.

Fig. 2

Fig. 2a, 2b: Large, widespread warts as a manifestation of severe human papilloma virus infection in a 15 year old female with DOCK8 deficiency. Fig. 2c: Extensive molluscum contagiosum in a patient with DOCK8 deficiency.

Fig. 3

Computed tomography of the chest of a 15 year old female with DOCK8 deficiency shows right middle lobe bronchiectasis with thickened bronchial walls.

Fig. 4

Magnetic resonance angiography demonstrates vasculopathy in a 19 year old patient with DOCK8 deficiency. Shown below are a dilated ascending and transverse thoracic aorta with diffuse irregularity and foci of narrowing in the descending aorta. Other findings (not shown) included narrowing at the bifurcation of the right brachial cephalic artery, dilatation of the right subclavian artery at its origin, narrowing of the left common carotid, narrowing of the common iliacs, and narrowing of the right external iliac artery.