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  3. ICF syndrome
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ICF syndrome


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Other Names:
Immunodeficiency-centromeric instability-facial anomalies syndrome; Immunodeficiency syndrome, variable; Centromeric instability, immunodeficiency syndrome; Immunodeficiency-centromeric instability-facial anomalies syndrome; Immunodeficiency syndrome, variable; Centromeric instability, immunodeficiency syndrome; CIID; Immune deficiency, variable, with centromeric instability of chromosomes 1, 9, and 16 See More
Categories:
Congenital and Genetic Diseases; Immune System Diseases
This disease is grouped under:
T cell immunodeficiency primary

Summary Summary


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The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 2268

Definition
The Immunodeficiency, Centromeric region instability, Facial anomalies syndrome (ICF) is a rare autosomal recessive disease characterized by immunodeficiency, although B cells are present, and by characteristic rearrangements in the vicinity of the centromeres (the juxtacentromeric heterochromatin) of chromosomes 1 and 16 and sometimes 9.

Epidemiology
ICF has been described in about 50 patients worldwide.

Clinical description
Other variable symptoms of this probably under-diagnosed syndrome include mild facial dysmorphism, growth retardation, failure to thrive, and psychomotor retardation. Serum levels of IgG, IgM, IgE, and/or IgA are low, although the type of immunoglobulin deficiency is variable. Recurrent infections are the presenting symptom, usually in early childhood.

Etiology
ICF always involves limited hypomethylation of DNA and often arises from mutations in one of the DNA methyltransferase genes (DNMT3B). Much of this DNA hypomethylation is in the 1qh, 9qh, and 16qh, regions that are the site of whole-arm deletions, chromatid and chromosome breaks, stretching (decondensation), and multiradial chromosome junctions in mitogen-stimulated lymphocytes. By an unknown mechanism, the DNMT3B deficiency that causes ICF interferes with lymphogenesis (at a step after class switching) or lymphocyte activation.

Antenatal diagnosis
With the identification of DNMT3B as the affected gene in a majority of ICF patients, prenatal diagnosis of ICF is possible. However, given the variety of DNMT3B mutations, a first-degree affected relative should first have both alleles of this gene sequenced.

Management and treatment
Treatment almost always includes regular infusions of immunoglobulins, mostly intravenously. Recently, bone marrow transplantation has been tried.

Visit the Orphanet disease page for more resources.
Last updated: 3/1/2006

Symptoms Symptoms


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This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 36 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of chromosome stability 0003220
Decreased circulating antibody level 0004313
Micrognathia
Little lower jaw
Small jaw
Small lower jaw
[ more ]
0000347
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections
[ more ]
0002205
Short stature
Decreased body height
Small stature
[ more ]
0004322
30%-79% of people have these symptoms
Abnormality of neutrophils 0001874
Anemia
Low number of red blood cells or hemoglobin
0001903
Cellular immunodeficiency 0005374
Communicating hydrocephalus 0001334
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root
[ more ]
0005280
Global developmental delay 0001263
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ]
0001249
Lymphopenia
Decreased blood lymphocyte number
Low lymphocyte number
[ more ]
0001888
Macrocephaly
Increased size of skull
Large head
Large head circumference
[ more ]
0000256
Malabsorption
Intestinal malabsorption
0002024
5%-29% of people have these symptoms
Epicanthus
Eye folds
Prominent eye folds
[ more ]
0000286
Flat face
Flat facial shape
0012368
Hypertelorism
Wide-set eyes
Widely spaced eyes
[ more ]
0000316
Low-set ears
Low set ears
Lowset ears
[ more ]
0000369
Macroglossia
Abnormally large tongue
Increased size of tongue
Large tongue
[ more ]
0000158
Protruding tongue
Prominent tongue
Tongue sticking out of mouth
[ more ]
0010808
Umbilical hernia 0001537
Percent of people who have these symptoms is not available through HPO
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils
[ more ]
0000463
Autosomal recessive inheritance 0000007
Bronchiectasis
Permanent enlargement of the airways of the lungs
0002110
Chronic bronchitis 0004469
Decreased circulating IgA level 0002720
Diarrhea
Watery stool
0002014
Failure to thrive
Faltering weight
Weight faltering
[ more ]
0001508
Immunodeficiency
Decreased immune function
0002721
Increased circulating IgM level 0003496
Malar flattening
Zygomatic flattening
0000272
Pneumonia 0002090
Reduced natural killer cell count 0040218
Sinusitis
Sinus inflammation
0000246
T lymphocytopenia
Low T cell count
Reduced number of T cells
[ more ]
0005403
Showing of 36 |
Do you have more information about symptoms of this disease? We want to hear from you.
Last updated: 1/1/2021
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Find a Specialist Find a Specialist


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If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

  • To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More Learn More


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These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss ICF syndrome. Click on the link to view a sample search on this topic.

GARD Answers GARD Answers


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Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

Have a question? Contact a GARD Information Specialist.
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