ICF syndrome: High variability of the chromosomal phenotype and association with classical Hodgkin lymphoma

Abstract

We report on two sibs with ICF syndrome (immunodeficiency, centromeric heterochromatin instability, and facial anomalies) diagnosed in the elder brother based on the typical chromosomal abnormalities present in 56% of metaphases from cultured lymphocytes. In a previous cytogenetic analysis this diagnosis had been missed due to low manifestation of the ICF chromosomal phenotype. Hypomethylation of classical satellites 2 and 3, and of alpha-satellite DNA was shown in the lymphocytes of the younger sister. At 7 years of age the boy presented with hemiplegia due to tumerous invasion of the right brachial plexus. Histopathology revealed classical Hodgkin lymphoma, a neoplasia which might have been facilitated by the underlying genetic defect.

Clinical spectrum of immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome)

“…Haematological malignancies were reported in two patients and included one patient who developed a classical Hodgkin lymphoma (patient 37),25 and a second patient who developed myelodysplastic syndrome (patient 24). Patient 45 developed aplastic anaemia.…”

Immunodeficiency, centromeric instability, facial anomalies (ICF) syndrome, due to ZBTB24 mutations, presenting with large cerebral cyst

“…Developmental delay and intellectual disability are often seen in affected patients [Ehrlich et al, 2006]. Hematological diseases and malignancies including macrophage activation syndrome, myelodysplastic syndrome, Hodgkin lymphoma, adrenocortical adenoma, and angiosarcoma have been reported in some affected patients [Andre et al, 2004; Schuetz et al, 2007; Hagleitner et al, 2008; van den Brand et al, 2011]. Life expectancy of ICF patients is significantly reduced because of severe immunodeficiency leading to recurrent, severe and often fatal respiratory and gastrointestinal infections.…”

Angiosarcoma in a patient with immunodeficiency, centromeric region instability, facial anomalies (ICF) syndrome

“…This is the first report of a non-hematological malignancy in a patient with the ICF syndrome. Up to now, reports of malignancy in the ICF syndrome are limited to one ICF type 1 patient with myelodysplastic syndrome and one ICF type 2 patient with Hodgkin lymphoma [Schuetz et al, 2007;Hagleitner et al, 2008]. Another type 2 patient had an adrenocortical adenoma [Kubota et al, 2004].…”

“…The major cause of death in ICF is infection [Hagleitner et al, 2008]. Hematological disease and malignancy (macrophage activation syndrome, myelodysplastic syndrome, and Hodgkin lymphoma) have been reported in three patients [Andr e et al, 2004;Schuetz et al, 2007;Hagleitner et al, 2008]. To date there have been no reports of either epithelial or mesenchymal malignancies.…”