Key Clinical and Laboratory Features

  • Common clinical features: Recurrent bacterial sinopulmonary infections (typically not staphylococcal pneumonias like Hyper-IgE syndrome), severe atopic disease (asthma, allergies, anaphylaxis), eczema, and extensive cutaneous viral infections (Molluscum contagiosum, HPV, Varicella zoster) and susceptibility to cancer (lymphomas and cutaneous malignancies (HPV).
  • Other clinical features: Recurrent skin abscesses and staphylococcal skin infections, mucocutaneous candidiasis, recurrent bowel infections (salmonella, giardia), cerebral vasculitis, autoimmune hemolytic anemia
  • Physical exam: Eczema, severe and extensive cutaneous viral infections (HPV, Molluscum contagiousum)
  • Common laboratory features: Lymphopenia (CD4+ T cells often most affected), decreased Th17 cells, immunoglobulin abnormalities (IgE elevated, IgM often low, IgG and IgA often normal), low T-cell numbers and NK-cell numbers, hypogammaglobulinemia (markedly low IgG level that becomes apparent after the loss of maternal antibodies as well as low or absent IgM and IgA), poor specific-antibody responses.

Testing Approach

  Test Comments
Gene DOCK8 Gene Sequencing   The DOCK8 gene is large (48 exons) and difficult to sequence. The majority of patients with DOCK8 deficiency have deletions or gene rearrangements within the DOCK8 gene locus that may not be easily identified by traditional Sanger sequencing approaches like those we offer. Because of this, clinical tests to evaluate copy number variants of all exons of the DOCK8 gene (like the DOCK8 Del/Dup test offered by GeneDx) are recommended as the first approach to assess the DOCK8 gene. This can be followed by Sanger sequencing of the full DOCK8 gene to identify specific missense or nonsense mutations.
Protein DOCK8 Protein Flow   Virtually all patients with DOCK8 deficiency have large deletions or gene rearrangements in the DOCK8 gene locus so cells do not express DOCK8 protein. The protein test is estimated to be at least 95% sensitive to detect affected patients.
Function N/A There are currently no available clinical tests to evaluate DOCK8 protein function.
  • Complete blood count with differential: Lymphopenia is common.
  • Lymphocyte subset analysis: CD4+ T cell lymphopenia is common but may also involve other subsets.
  • Th17 cell enumeration: Th17 cells are typically low.
  • Quantitative immunoglobulin levels: IgE elevated, IgM low, IgG and IgA often normal.
  • Specific antibody titers are typically low.