Immunophenotype, Karyotype and Molecular Findings in a Case of ICF Syndrome

Excerpt

Immunodeficiency, centromere instability and facial anomalies (ICF) syndrome is a rare type of primary immunodeficiency disorder (PID) classified under combined immunodeficiencies with syndromic features in the IUIS classification [1]. Based on the underlying gene defect, four distinct subtypes of ICF syndrome have been characterized: ICF1 (DNMT3B), ICF2 (ZBTB24), ICF3 (CDCA7) and ICF4 (HELLS) [2, 3]. All four subtypes have an autosomal recessive inheritance with a severe immunodeficiency phenotype caused by reduced levels or absence of serum immunoglobulins. Apart from immunodeficiency and facial dysmorphism, the disease is characterised by the characteristic karyotype abnormalities because of the centromere instability. Following phytohemagglutinin (PHA) stimulation, aberrant multiradial configurations are seen with chromosomes 1, 9, and 16. The combination of a defective humoral immune response with normal or reduced B cell and T cell counts, facial anomalies and cytogenetic multiradial configurations is typical for all ICF syndrome patients [4]. …