The Immunodeficiency, Centromeric Instability, Facial Anomalies (ICF) Syndrome is a rare immunodeficiency disorder that is often fatal in early childhood unless aggressively treated.
Inheritance: autosomal recessive
There are multiple affected genetic loci with the 2 most common:
(1) DNMT3B (DNA methyltransferase 3 beta at 20q11.21, associated with ICF1)
(2) ZBTB24 (zinc finger and BTB domain containing 24 at 6q21, associated with ICF2)
Clinical and laboratory features:
(1) facial abnormalities ("bird-like", round face, flat nasal bridge, hypertelorism, epicanthus, macroglossia, up-turned nose, micrognathia, low-set ears)
(2) recurrent bacterial and viral infections, especially involving the respiratory and GI tracts
(3) bronchiectasis
(4) failure to thrive
(5) variable developmental delay (speech, other)
(6) autoimmune disease (hepatitis, nephritis, thyroiditis)
(7) variable cirrhosis
(8) variable risk for malignancy with longer survival
Laboratory findings:
(1) hypo- or agammaglobulinemia
(2) absence of (a) CD19 and CD27 positive memory B-cells and (b) gut plasma cells
(3) variable defects in T cell proliferation
(4) variable pancytopenia
(5) chromosomal abnormalities affecting chromosomes 1, 9 and 16 (centromeric region breaks and deletions, centromeric region decondensation, multi-branched chromosomes)
The presence of both immunoglobulin and lymphocyte abnormalities indicates a combined immunodeficiency.
