RESUMEN
Immunodeficiency with centromeric instability and facial anomalies (ICF) syndrome is a primary immunodeficiency, predominantly characterized by agammaglobulinemia or hypoimmunoglobulinemia, centromere instability and facial anomalies. Mutations in two genes have been discovered to cause ICF syndrome: DNMT3B and ZBTB24. To characterize the clinical features of this syndrome, as well as genotype-phenotype correlations, we compared clinical and genetic data of 44 ICF patients. Of them, 23 had mutations in DNMT3B (ICF1), 13 patients had mutations in ZBTB24 (ICF2), whereas for 8 patients, the gene defect has not yet been identified (ICFX). While at first sight these patients share the same immunological, morphological and epigenetic hallmarks of the disease, systematic evaluation of all reported informative cases shows that: (1) the humoral immunodeficiency is generally more pronounced in ICF1 patients, (2) B- and T-cell compartments are both involved in ICF1 and ICF2, (3) ICF2 patients have a significantly higher incidence of intellectual disability and (4) congenital malformations can be observed in some ICF1 and ICF2 cases. It is expected that these observations on prevalence and clinical presentation will facilitate mutation-screening strategies and help in diagnostic counseling.
Asunto(s)
ADN (Citosina-5-)-Metiltransferasas/genética , Cara/anomalías , Heterogeneidad Genética , Predisposición Genética a la Enfermedad , Síndromes de Inmunodeficiencia/genética , Mutación/genética , Proteínas Represoras/genética , Adolescente , Adulto , Niño , Demografía , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Inmunoglobulina G/sangre , Síndromes de Inmunodeficiencia/sangre , Síndromes de Inmunodeficiencia/terapia , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Enfermedades de Inmunodeficiencia Primaria , Adulto Joven , ADN Metiltransferasa 3BRESUMEN
Severe combined immunodeficiency (SCID) is one of the most severe forms of primary immunodeficiency characterized by absence of functional T lymphocytes. It is a paediatric emergency, which is life-threatening when recognized too late. The clinical presentation varies from the classical form of SCID through atypical SCID to Omenn syndrome. In addition, there is a considerable immunological variation, which can hamper the diagnosis. In this educational review, we describe the immunopathological background, clinical presentations and diagnostic process of SCID, as well as the therapeutic possibilities.