MCID: IMM011
MIFTS: 44

Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome

Categories: Rare diseases, Blood diseases, Genetic diseases, Immune diseases

Aliases & Classifications for Immunodeficiency-Centromeric Instability-Facial Anomalies...

MalaCards integrated aliases for Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome:

Name: Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome 12 53 59 15 40
Icf Syndrome 12 76 53 59 55
Immunodeficiency Syndrome, Variable 53 73
Icf 76 3
Immune Deficiency, Variable, with Centromeric Instability of Chromosomes 1, 9, and 16 53
Centromeric Instability, Immunodeficiency Syndrome 53
Ciid 53

Characteristics:

Orphanet epidemiological data:

59
icf syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

Classifications:

Orphanet: 59  
Rare immunological diseases


Summaries for Immunodeficiency-Centromeric Instability-Facial Anomalies...

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 2268Disease definitionThe 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.EpidemiologyICF has been described in about 50 patients worldwide.Clinical descriptionOther 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.EtiologyICF 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 diagnosisWith 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 treatmentTreatment almost always includes regular infusions of immunoglobulins, mostly intravenously. Recently, bone marrow transplantation has been tried.Visit the Orphanet disease page for more resources.

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 immunodeficiency-centromeric instability-facial anomalies syndrome 4, 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 One carbon pool by folate and Sulfur amino acid metabolism. Affiliated tissues include bone marrow, b cells and bone, and related phenotypes are macroglossia and macrocephaly

CDC : 3 After ten years of international revision efforts coordinated by the World Health Organization (WHO), the World Health Assembly on May 22, 2001, approved the International Classification of Functioning, Disability and Health and its abbreviation of "ICF." This classification was first created in 1980 (and then called the International Classification of Impairments, Disabilities, and Handicaps, or ICIDH) by WHO to provide a unifying framework for classifying the consequences of disease.

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

Wikipedia : 76 ICF syndrome (or Immunodeficiency, Centromere instability and Facial anomalies syndrome) is a very rare... more...

Related Diseases for Immunodeficiency-Centromeric Instability-Facial Anomalies...

Diseases related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 91)
# Related Disease Score Top Affiliating Genes
1 immunodeficiency-centromeric instability-facial anomalies syndrome 2 35.4 LOC105377935 MICAL1 ZBTB24
2 immunodeficiency-centromeric instability-facial anomalies syndrome 4 12.9
3 immunodeficiency-centromeric instability-facial anomalies syndrome 3 12.9
4 immunodeficiency-centromeric instability-facial anomalies syndrome 1 12.8
5 kabuki syndrome 1 10.7 DNMT3B LOC105377935 ZBTB24
6 selective igg deficiency disease 10.6 CD40LG CD79A
7 c1q nephropathy 10.6 CD40LG CD79A
8 meningovascular neurosyphilis 10.5 CD40LG CD79A
9 alpha chain disease 10.5 CD40LG CD79A
10 brill-zinsser disease 10.5 CD40LG CD79A
11 exudative glomerulonephritis 10.5 CD40LG CD79A
12 cork-handlers' disease 10.5 CD40LG CD79A
13 salpingo-oophoritis 10.5 CD40LG CD79A
14 early yaws 10.5 CD40LG CD79A
15 ventilation pneumonitis 10.5 CD40LG CD79A
16 chronic interstitial cystitis 10.5 CD40LG CD79A
17 axillary adenitis 10.5 CD40LG CD79A
18 cryofibrinogenemia 10.5 CD40LG CD79A
19 trichostrongyloidiasis 10.5 CD40LG CD79A
20 subacute bacterial endocarditis 10.5 CD40LG CD79A
21 heterophyiasis 10.5 CD40LG CD79A
22 immunoglobulin g deficiency 10.5 CD40LG CD79A
23 orbital granuloma 10.5 CD40LG CD79A
24 transient hypogammaglobulinemia of infancy 10.5 CD40LG CD79A
25 hyperglobulinemic purpura 10.5 CD40LG CD79A
26 gastroduodenitis 10.5 CD40LG CD79A
27 bacterial conjunctivitis 10.5 CD40LG CD79A
28 heavy chain disease 10.5 CD40LG CD79A
29 ophthalmia neonatorum 10.5 CD40LG CD79A
30 immunoglobulin a deficiency 1 10.5 CD40LG CD79A
31 parotid disease 10.5 CD40LG CD79A
32 cerebral arteritis 10.5 CD40LG CD79A
33 selective immunoglobulin deficiency disease 10.5 CD40LG CD79A
34 geniculate herpes zoster 10.5 CD40LG CD79A
35 erythema elevatum diutinum 10.5 CD40LG CD79A
36 sporotrichosis 10.5 CD40LG CD79A
37 fallopian tube disease 10.5 CD40LG CD79A
38 hyperimmunoglobulin syndrome 10.5 CD40LG CD79A
39 congenital syphilis 10.5 CD40LG CD79A
40 polyclonal hypergammaglobulinemia 10.5 CD40LG CD79A
41 monoclonal paraproteinemia 10.5 CD40LG CD79A
42 salpingitis 10.5 CD40LG CD79A
43 ocular toxoplasmosis 10.5 CD40LG CD79A
44 dysgammaglobulinemia 10.5 CD40LG CD79A
45 congenital hypogammaglobulinemia 10.5 CD40LG CD79A
46 acute maxillary sinusitis 10.5 CD40LG CD79A
47 chronic polyneuropathy 10.5 CD40LG CD79A
48 spinocerebellar ataxia, autosomal recessive 10 10.5 CD40LG CD79A
49 parasitic ichthyosporea infectious disease 10.4 CD40LG CD79A
50 cd40 ligand deficiency 10.4 CD40LG CD79A

Graphical network of the top 20 diseases related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome:



Diseases related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome

Symptoms & Phenotypes for Immunodeficiency-Centromeric Instability-Facial Anomalies...

Human phenotypes related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome:

59 32 (show all 23)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macroglossia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000158
2 macrocephaly 59 32 frequent (33%) Frequent (79-30%) HP:0000256
3 epicanthus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000286
4 hypertelorism 59 32 occasional (7.5%) Occasional (29-5%) HP:0000316
5 micrognathia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000347
6 low-set ears 59 32 occasional (7.5%) Occasional (29-5%) HP:0000369
7 intellectual disability 59 32 frequent (33%) Frequent (79-30%) HP:0001249
8 global developmental delay 59 32 frequent (33%) Frequent (79-30%) HP:0001263
9 communicating hydrocephalus 59 32 frequent (33%) Frequent (79-30%) HP:0001334
10 umbilical hernia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001537
11 abnormality of neutrophils 59 32 frequent (33%) Frequent (79-30%) HP:0001874
12 lymphopenia 59 32 frequent (33%) Frequent (79-30%) HP:0001888
13 anemia 59 32 frequent (33%) Frequent (79-30%) HP:0001903
14 malabsorption 59 32 frequent (33%) Frequent (79-30%) HP:0002024
15 recurrent respiratory infections 59 32 hallmark (90%) Very frequent (99-80%) HP:0002205
16 abnormality of chromosome stability 59 32 hallmark (90%) Very frequent (99-80%) HP:0003220
17 decreased antibody level in blood 59 32 hallmark (90%) Very frequent (99-80%) HP:0004313
18 short stature 59 32 hallmark (90%) Very frequent (99-80%) HP:0004322
19 depressed nasal bridge 59 32 frequent (33%) Frequent (79-30%) HP:0005280
20 cellular immunodeficiency 59 32 frequent (33%) Frequent (79-30%) HP:0005374
21 protruding tongue 59 32 occasional (7.5%) Occasional (29-5%) HP:0010808
22 flat face 59 32 occasional (7.5%) Occasional (29-5%) HP:0012368
23 immunodeficiency 59 Very frequent (99-80%)

UMLS symptoms related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome:


diarrhea

MGI Mouse Phenotypes related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.32 CD40LG CD79A DNMT1 DNMT3A DNMT3B DNMT3L

Drugs & Therapeutics for Immunodeficiency-Centromeric Instability-Facial Anomalies...

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Neuro-orthopaedic Surgery in the Treatment of the Spastic Equinovarus Foot Completed NCT01265238

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

Genetic Tests for Immunodeficiency-Centromeric Instability-Facial Anomalies...

Anatomical Context for Immunodeficiency-Centromeric Instability-Facial Anomalies...

MalaCards organs/tissues related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome:

41
Bone Marrow, B Cells, Bone, Neutrophil, Tongue

Publications for Immunodeficiency-Centromeric Instability-Facial Anomalies...

Articles related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome:

# Title Authors Year
1
Corrigendum: Mutations in CDCA7 and HELLS cause immunodeficiency-centromeric instability-facial anomalies syndrome. ( 27328760 )
2016
2
Mutations in CDCA7 and HELLS cause immunodeficiency-centromeric instability-facial anomalies syndrome. ( 26216346 )
2015
3
Combined immunodeficiency develops with age in Immunodeficiency-centromeric instability-facial anomalies syndrome 2 (ICF2). ( 25330735 )
2014
4
Variability of clinical and immunological phenotype in immunodeficiency-centromeric instability-facial anomalies syndrome. Report of two new patients and review of the literature. ( 8529685 )
1995

Variations for Immunodeficiency-Centromeric Instability-Facial Anomalies...

Expression for Immunodeficiency-Centromeric Instability-Facial Anomalies...

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

Pathways for Immunodeficiency-Centromeric Instability-Facial Anomalies...

Pathways related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.71 DNMT1 DNMT3A DNMT3B DNMT3L
2
Show member pathways
11.63 DNMT1 DNMT3A DNMT3B
3 11.51 CBX5 DNMT1 DNMT3A DNMT3B HELLS MECP2
4
Show member pathways
10.97 DNMT1 DNMT3A DNMT3B MECP2
5 10.67 DNMT1 DNMT3A DNMT3B
6
Show member pathways
10.44 DNMT1 MECP2

GO Terms for Immunodeficiency-Centromeric Instability-Facial Anomalies...

Cellular components related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromosome, centromeric region GO:0000775 9.33 CBX5 DNMT3A HELLS
2 nuclear heterochromatin GO:0005720 9.26 CBX5 DNMT3A
3 pericentric heterochromatin GO:0005721 9.13 CBX5 DNMT1 HELLS
4 heterochromatin GO:0000792 8.92 CBX5 DNMT1 DNMT3A MECP2

Biological processes related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome according to GeneCards Suite gene sharing:

(show all 16)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of transcription by RNA polymerase II GO:0000122 9.96 CBX5 DNMT1 DNMT3A DNMT3B MECP2
2 negative regulation of transcription, DNA-templated GO:0045892 9.89 CBX5 DNMT1 DNMT3B DNMT3L MECP2
3 regulation of gene expression GO:0010468 9.78 DNMT1 DNMT3A DNMT3B MECP2
4 response to vitamin A GO:0033189 9.55 DNMT3A DNMT3B
5 DNA methylation involved in gamete generation GO:0043046 9.54 DNMT3A DNMT3L
6 negative regulation of gene expression, epigenetic GO:0045814 9.54 DNMT1 DNMT3A DNMT3B
7 positive regulation of histone H3-K4 methylation GO:0051571 9.52 DNMT1 DNMT3B
8 methylation-dependent chromatin silencing GO:0006346 9.51 DNMT3A HELLS
9 maintenance of DNA methylation GO:0010216 9.46 DNMT1 HELLS
10 DNA methylation involved in embryo development GO:0043045 9.43 DNMT1 DNMT3A
11 regulation of gene expression by genetic imprinting GO:0006349 9.43 DNMT3A DNMT3L MECP2
12 negative regulation of histone H3-K9 methylation GO:0051573 9.4 DNMT1 DNMT3B
13 C-5 methylation of cytosine GO:0090116 9.33 DNMT1 DNMT3A DNMT3B
14 positive regulation of DNA methylation GO:1905643 9.32 DNMT3L MECP2
15 DNA methylation on cytosine GO:0032776 9.13 DNMT1 DNMT3A DNMT3L
16 DNA methylation GO:0006306 9.02 DNMT1 DNMT3A DNMT3B DNMT3L HELLS

Molecular functions related to Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromatin binding GO:0003682 9.63 CBX5 DNMT1 DNMT3A DNMT3B HELLS MECP2
2 methyl-CpG binding GO:0008327 9.26 DNMT1 MECP2
3 DNA-methyltransferase activity GO:0009008 9.13 DNMT1 DNMT3A DNMT3B
4 DNA (cytosine-5-)-methyltransferase activity GO:0003886 8.8 DNMT1 DNMT3A DNMT3B

Sources for Immunodeficiency-Centromeric Instability-Facial Anomalies...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
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42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
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54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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