Immunodeficiency–centromeric instability–facial anomalies syndrome

ICF syndrome (or Immunodeficiency, Centromere instability and Facial anomalies syndrome) is a very rare autosomal recessive immune disorder.

Presentation

It is characterized by variable reductions in serum immunoglobulin levels which cause most ICF patients to succumb to infectious diseases before adulthood. ICF syndrome patients exhibit facial anomalies which include hypertelorism, low-set ears, epicanthal folds and macroglossia.

Genetics

Mutations in four genes can cause this syndrome: Cell division cycle associated protein 7 (CDCA7), DNA-methyltransferase 3b (DNMT3B), Lymphoid specific helicase (HELLS) and Zinc finger- and BTB domain containing protein 24 (ZBTB24).

The CDCA7 gene is located on chromosome 2 (2q31.1).

The DNMT3B gene is located on chromosome 20 (20q11.2)).

The HELLS gene is located on chromosome 10 (10q23.33)

The ZBTB24 gene is located on chromosome 6 (6q21)

This disease is inherited in an autosomal recessive manner.

Treatment

For ICF patients the most diffused therapy consists of repeated intravenous infusions of immunoglobulins for the patients entire lifespan. In 2007, Gennery et al. cured the humoral and cellular immunological defect in three ICF1 patients by hematopoietic stem cell transplantation (HSCT). The only side effect was related to the development of autoimmune phenomena in two of them. This is the only documented case of restoring the immune conditions and growth improvement in these patients.

See also

• Bare lymphocyte syndrome
• List of cutaneous conditions

External links

Classification	ICD-10: D84.8 OMIM: 242860 DiseasesDB: 32366
External resources	Orphanet: 2268

• Orphanet Journal of Rare Diseases link to ICF syndrome [1]