Immunodeficiency–centromeric instability–facial anomalies syndrome
Template:Refimprove Template:Infobox medical condition (new) ICF syndrome (or Immunodeficiency, Centromere instability and Facial anomalies syndrome)<ref>{{#ifeq:|none||{{#switch: | short = OMIM: | shortlink = OMIM: | plain = Online Mendelian Inheritance in Man: | full | #default = Online Mendelian Inheritance in Man (OMIM):}}}} {{#if: |{{{2}}} - }} 242860</ref> is a very rare autosomal recessive<ref name="pmid7557962">Template:Cite journal</ref> immune disorder.
Presentation
It is characterized by variable reductions in serum immunoglobulin (IgG, IgM and/or IgA) 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.<ref name="Orphanet">Template:Cite journal</ref> Other frequent symptoms observed in individuals with ICF syndrome include intellectual disability, recurrent and prolonged respiratory infections, and integumentary and digestive system infections.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
Genetics
Mutations in four genes can cause this syndrome:<ref name="Ren2019">Ren R, Hardikar S, Horton JR, Lu Y, Zeng Y, Singh AK, Lin K, Coletta LD, Shen J, Lin Kong CS, Hashimoto H, Zhang X, Chen T, Cheng X (2019) Structural basis of specific DNA binding by the transcription factor ZBTB24. Nucleic Acids Res</ref> 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).Template:Cn
The CDCA7 gene is located on chromosome 2 (2q31.1),Template:Cn the DNMT3B gene on chromosome 20 (20q11.2)).<ref name="pmid15580563">Template:Cite journal</ref><ref>{{#ifeq:|none||{{#switch: | short = OMIM: | shortlink = OMIM: | plain = Online Mendelian Inheritance in Man: | full | #default = Online Mendelian Inheritance in Man (OMIM):}}}} {{#if: |{{{2}}} - }} 602900</ref> the HELLS gene on chromosome 10 (10q23.33), and the ZBTB24 gene on chromosome 6 (6q21).Template:Cn
This disease is inherited in an autosomal recessive manner.<ref name="pmid7557962" />
Diagnosis
Diagnosis can occur using a karyotype or linkage analysis or DNA sequence analysis. This can occur prior to birth in families with a known history of the condition. <ref name="Orphanet" />
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.<ref>Template:Cite journal</ref> This is the only documented case of restoring the immune conditions and growth improvement in these patients.<ref>https://www.ptglab.com/news/blog/icf-syndrome-a-gene-silencing-chromatin-disorder/ IFC Syndrome: A gene silencing chromatin disorder</ref>
See also
References
External links
- Orphanet Journal of Rare Diseases link to ICF syndrome [1]