Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome (ICF)

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Disease Ontology 12 DOID:0090007 KEGG 36 H02308 ICD10 32 D84.8 ICD10 via Orphanet 33 D84.8

Orphanet 58 ORPHA2268 SNOMED-CT via HPO 68 119250001 165397008 194021007 22006008 224958001 228156007 237836003 247578003 249872000 250274006 25273001 271569006 271737000 285503005 32958008 396347007 48813009 91138005 95515009 more UMLS 70 C0398788

GARD : ²⁰ The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. 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.

MalaCards based summary : Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome, also known as icf syndrome, is related to immunodeficiency-centromeric instability-facial anomalies syndrome 2 and respiratory papillomatosis, juvenile recurrent, congenital, and has symptoms including diarrhea An important gene associated with Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome is DNMT3B (DNA Methyltransferase 3 Beta), and among its related pathways/superpathways are Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 and Sulfur amino acid metabolism. Affiliated tissues include b cells, bone marrow and tongue, and related phenotypes are recurrent respiratory infections and short stature

Disease Ontology : ¹² A syndrome characterized by immunodeficiency, rearrangements in the vicinity of the centromeres of chromosomes 1, 9, and 16 and facial anomalies in most cases.

KEGG : ³⁶ Immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome) is a genetically heterogeneous autosomal recessive disorder. It is characterized by recurrent and often fatal respiratory and gastrointestinal infections as a consequence of hypogammaglobulinemia in the presence of B cells. Nearly all patients also present with distinct facial anomalies. Centromeric instability is the cytogenetic hallmark of ICF syndrome. Mutations in the DNA methyltransferase 3B (DNMT3B) gene account for about 50% of ICF cases, while about 30% of cases have mutations in the ZBTB24 gene. Recently, it has been reported that mutations in CDCA7 and HELLS cause ICF syndrome.

Wikipedia : ⁷³ ICF syndrome (or Immunodeficiency, Centromere instability and Facial anomalies syndrome) is a very rare... more...

Search Clinical Trials , NIH Clinical Center for Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome

Search GEO for disease gene expression data for Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome.