ICF syndrome
Synonyms: Immunodeficiency-centromeric instability-facial anomalies syndrome · Immunodeficiency-centromeric instability-facial dysmorphism syndrome
- Type
- Malformation syndrome
- Group
- Disorder
- Inheritance
- Autosomal recessive
- Age of onset
- Childhood
- Status
- active
A rare autosomal recessive syndrome with combined immunodeficiency characterized by the clinical triad of immunodeficiency, centromeric instability and facial anomalies (abbreviated ICF syndrome). The immunodeficiency is with panhypogammaglobulinemia, and a lack of memory (CD19+CD27+) B cells in the peripheral blood, although B and T-cell counts are normal. Anomalies and rearrangements associated with DNA hypomethylation in the vicinity of the centromeres (the juxtacentromeric heterochromatin) of chromosomes 1 and 16 and sometimes 9, in mitogen-stimulated lymphocytes, is a hallmark of the syndrome. The typical facial anomalies include hypertelorism, low-set ears, epicanthus and macroglossia.
Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | ICF syndrome | Immunodeficiency-centromeric instability-facial anomalies syndrome · Immunodeficiency-centromeric instability-facial dysmorphism syndrome |
| fr | Syndrome ICF | Syndrome d'instabilité centromérique-immunodéficience-dysmorphie faciale · Syndrome d'instabilité de l'hétérochromatine paracentromérique-immunodéficience combinée-dysmorphie faciale |
| de | ICF-Syndrom | Immunodefizienz-Zentromerinstabilität-faziale Anomalien-Syndrom |
| es | Síndrome ICF | Síndrome de inmunodeficiencia-inestabilidad centromérica-anomalías faciales · Síndrome de inmunodeficiencia-inestabilidad centromérica-dismorfia facial |
| it | Sindrome ICF | Instabilità centromerica - immunodeficienza - dismorfismi · Sindrome immunodeficienza-instabilità centromerica-anomalie facciali · Sindrome immunodeficienza-instabilità centromerica-dismorfismi facciali |
| nl | ICF-syndroom | Immuundeficiëntie - centromeerinstabiliteit - faciale anomalieën-syndroom · Immuundeficiëntie - centromeerinstabiliteit - faciale dysmorfie-syndroom |
| pt | Síndrome ICF | Síndrome de imunodeficiência-instabilidade centromérica-anomalias faciais · Síndrome de imunodeficiência-instabilidade centromérica-dismorfia facial · Síndrome de instabilidade centromérica-imunodeficiência |
| pl | Zespół ICF | Niedobór odporności - niestabilność centromeryczna - anomalie twarzy |
| cs | ICF syndrom | Imunodeficience spojená s centromerickou nestabilitou a faciálním dysmorfismem · ICF |
| uk | Синдром ICF | Синдром імунодефіциту-центромерної нестабільності-лицьових аномалій · Синдром імунодефіциту-центромерної нестабільності-лицевого дисморфізму |
| zh | ICF综合征 | 免疫缺陷-着丝粒不稳定-面部异常综合征 |
| tr | ICF sendromu | İmmün yetmezlik-sentromerik instabilite-fasiyal anomalileri sendromu |
Definition in:
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 242860 | BTNT | validated | |
| OMIM | 614069 | BTNT | validated | |
| OMIM | 616910 | BTNT | validated | |
| OMIM | 616911 | BTNT | validated | |
| ICD-10 | D84.8 | NTBT | attributed | validated |
| ICD-11 | 4A01.00 | NTBT | index | validated |
| MONDO | 0000133 | E | validated | |
| UMLS | C0398788 | E | validated | |
| GARD | 2945 | E | validated |
E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.
Classification
Preferential parent (Orphanet linearisation):
Parents in the classifications (3):
- ORPHA:169346DNA repair defect other than combined T-cell and B-cell immunodeficiencies
rare genetic diseases; rare immunological diseases; rare transplant-related disorders - ORPHA:717757Rare immune disease with inflammatory bowel disease
rare gastroenterological diseases; rare genetic diseases; rare transplant-related disorders - ORPHA:611314Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome
rare genetic diseases; rare neurological diseases
No children.
Genes
5 direct| Gene | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|
| CDCA7 | Disease-causing germline mutation(s) in | Assessed | HGNC:14628 | ENSG00000144354 | 609937 | 2q31.1 | cell division cycle associated 7 | 26216346[PMID] |
| DNMT3B | Disease-causing germline mutation(s) in | Assessed | HGNC:2979 | ENSG00000088305 | 602900 | 20q11.21 | DNA methyltransferase 3 beta | 10588719[PMID] |
| HELLS | Disease-causing germline mutation(s) in | Assessed | HGNC:4861 | ENSG00000119969 | 603946 | 10q23.33 | helicase, lymphoid specific | 26216346[PMID] |
| UHRF1 | Disease-causing germline mutation(s) in | Assessed | HGNC:12556 | ENSG00000276043 | 607990 | 19p13.3 | ubiquitin like with PHD and ring finger domains 1 | 36458887[PMID] |
| ZBTB24 | Disease-causing germline mutation(s) in | Assessed | HGNC:21143 | ENSG00000112365 | 614064 | 6q21 | zinc finger and BTB domain containing 24 | 21906047[PMID] |
Prevalence and incidence
2 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Cases/families | 66 cases | Worldwide | Case(s) | Validated | 23486536[PMID] | |
| Point prevalence | <1 / 1 000 000 | — | Worldwide | Class only | Validated | ORPHANET |
Value is Orphadata's ValMoy: the mean estimate per 100 000 for prevalence and incidence, the number of cases or families for case reports.
HPO phenotypes
23 annotations · validated 2016-06-01| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Very frequent (99-80%) | ||
| HP:0003220 | Abnormality of chromosome stability | |
| HP:0004313 | Decreased circulating antibody level | |
| HP:0002721 | Immunodeficiency | |
| HP:0000347 | Micrognathia | |
| HP:0002205 | Recurrent respiratory infections | |
| HP:0004322 | Short stature | |
| Frequent (79-30%) | ||
| HP:0001874 | Abnormality of neutrophils | |
| HP:0001903 | Anemia | |
| HP:0005374 | Cellular immunodeficiency | |
| HP:0001334 | Communicating hydrocephalus | |
| HP:0005280 | Depressed nasal bridge | |
| HP:0001263 | Global developmental delay | |
| HP:0001249 | Intellectual disability | |
| HP:0001888 | Lymphopenia | |
| HP:0000256 | Macrocephaly | |
| HP:0002024 | Malabsorption | |
| Occasional (29-5%) | ||
| HP:0000286 | Epicanthus | |
| HP:0012368 | Flat face | |
| HP:0000316 | Hypertelorism | |
| HP:0000369 | Low-set ears | |
| HP:0000158 | Macroglossia | |
| HP:0010808 | Protruding tongue | |
| HP:0001537 | Umbilical hernia | |
Run the differential on the 6 obligate / very frequent terms
Sources for this card
- Orphanet page: orpha.net/en/disease/detail/2268
- This record as JSON: /data/d/2268.json