ICF syndrome is a rare autosomal recessive genetic disorder characterised by Immunodeficiency, Centrometric instability and Facial anomalies. Up to now 20 patients have been reported. We describe an 8 year-old female patient with typical signs of ICFS such as immunodeficiency (at age 1 ½ years decreased IgM, IgG, IgA ad IgE levels, low values of IgG 1-3 subclasses, decreased number of B cells), facial anomalies (hypertelorism, bilateral epicanthic folds, broad and flat nasal bridge, protruding tongue) and the typical chromosomal abnormalities in the heterochromatic regions of chromosomes 1, 16 and 9 (stretching, breaks, triradial figures and multibranched configurations). Methylation studies of our patient showed a marked hypomethylation of satellite 2 DNA (Schuffenhauer et al, 1995).

A review of the literature revealed that the clinical signs of ICFS show considerable variability. Facial dysmorphism can be absent. Immunodeficiency is the only consistent finding in all reported ICFS patients, but is expressed with large variability. Reduced levels of two or more immunoglobulin classes were found in all patients with ICFS. However, the severeness of immunoglobulin deficiency reaches from slight deficiency without infections to agammaglobulinemia and severe life-threatening infections. B cell and/or T cell counts may be normal, increased or reduced. The pathognomonic finding for diagnosis of ICFS is the heterochromatin instability in peripheral lymphocytes. Because of the variability of the phenotype, it is possible that many ICFS patients remain undiagnosed without karyotype analysis. Therefore, cytogenetic analyses, combined with DNA methylation studies, should be performed in all patients with unclassified B cell immunodeficiency.