ICF syndrome (or Immunodeficiency, Centromere instability and Facial anomalies syndrome) is a very rare

autosomal An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosome, allosomal (sex chromosome) pairs, which may have different structures. The DNA in au ...

recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

immune disorder An immune disorder is a dysfunction of the immune system. These disorders can be characterized in several different ways: * By the component(s) of the immune system affected * By whether the immune system is overactive or underactive * By whether t ...

Presentation

It is characterized by variable reductions in serum

immunoglobulin An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

levels which cause most ICF patients to succumb to

infectious disease An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...

s before

adulthood An adult is a human or other animal that has reached full growth. In human context, the term ''adult'' has meanings associated with social and legal concepts. In contrast to a " minor", a legal adult is a person who has attained the age of major ...

. ICF syndrome patients exhibit facial anomalies which include

hypertelorism Hypertelorism is an abnormally increased distance between two organs or bodily parts, usually referring to an increased distance between the orbits (eyes), or orbital hypertelorism. In this condition the distance between the inner eye corners as ...

low-set ears Low-set ears are a clinical feature in which the ears are positioned lower on the head than usual. They are present in many congenital conditions. Low-set ears are defined as outer ears positioned two or more standard deviations lower than the pop ...

epicanthal fold An epicanthic fold or epicanthus is a skin fold of the upper eyelid that covers the inner corner (medial canthus) of the eye. However, variation occurs in the nature of this feature and the possession of "partial epicanthic folds" or "slight ...

s and

macroglossia Macroglossia is the medical term for an unusually large tongue. Severe enlargement of the tongue can cause cosmetic and functional difficulties in speaking, eating, swallowing and sleeping. Macroglossia is uncommon, and usually occurs in children. ...

Genetics

Mutations in four

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

s can cause this syndrome: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 Cell division cycle associated protein 7 ( CDCA7), DNA-methyltransferase 3b (

DNMT3B DNA (cytosine-5)-methyltransferase 3 beta, is an enzyme that in humans in encoded by the DNMT3B gene. Mutation in this gene are associated with immunodeficiency, centromere instability and facial anomalies syndrome. Function CpG methylation i ...

), Lymphoid specific helicase ( HELLS) and Zinc finger- and BTB domain containing protein 24 ( ZBTB24). The CDCA7 gene is located on

chromosome 2 Chromosome 2 is one of the twenty-three pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 2 is the second-largest human chromosome, spanning more than 242 million base pairs and representing almost e ...

(2q31.1). The DNMT3B gene is located on

chromosome 20 Chromosome 20 is one of the 23 pairs of chromosomes in humans. Chromosome 20 spans around 66 million base pairs (the building material of DNA) and represents between 2 and 2.5 percent of the total DNA in cells. Chromosome 20 was fully sequenced ...

(20q11.2)). The HELLS gene is located on

chromosome 10 Chromosome 10 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 10 spans about 133 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the tota ...

(10q23.33) The ZBTB24 gene is located on

chromosome 6 Chromosome 6 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 6 spans more than 170 million base pairs (the building material of DNA) and represents between 5.5 and 6% of the total ...

(6q21) This disease is inherited in an autosomal

manner.

Diagnosis

Diagnosis can occur using a

karyotype A karyotype is the general appearance of the complete set of metaphase chromosomes in the cells of a species or in an individual organism, mainly including their sizes, numbers, and shapes. Karyotyping is the process by which a karyotype is disce ...

or linkage analysis or DNA sequence analysis. This can occur prior to birth in families with a known history of the condition.

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.https://www.ptglab.com/news/blog/icf-syndrome-a-gene-silencing-chromatin-disorder/ IFC Syndrome: A gene silencing chromatin disorder

References

External links