Immunodeficiency–centromeric instability–facial anomalies syndrome

Autosomal recessive - en

Immunodeficiency–centromeric instability–facial anomalies syndrome (ICF syndrome) is a rare genetic disorder characterized by a combination of immunodeficiency, centromeric instability, and distinctive facial anomalies. The syndrome is caused by mutations in genes involved in DNA methylation and chromatin structure, leading to defects in chromosome stability and immune function.

Clinical Features

Individuals with ICF syndrome typically present with:

• **Immunodeficiency**: Recurrent infections due to low levels of immunoglobulins and impaired function of B cells and T cells.
• **Centromeric instability**: Chromosomal abnormalities, particularly involving chromosomes 1, 9, and 16, which can be observed in karyotype analysis.
• **Facial anomalies**: Distinctive facial features such as a flat nasal bridge, epicanthal folds, and a high-arched palate.

Genetics

ICF syndrome is primarily associated with mutations in the DNMT3B gene, which encodes a DNA methyltransferase involved in the establishment of DNA methylation patterns. Other genes implicated in the syndrome include ZBTB24, CDCA7, and HELLS. The inheritance pattern of ICF syndrome is typically autosomal recessive.

Diagnosis

Diagnosis of ICF syndrome involves a combination of clinical evaluation, immunological testing, and genetic analysis. Key diagnostic criteria include:

• Reduced levels of serum immunoglobulins (IgG, IgA, and IgM).
• Chromosomal analysis showing centromeric instability.
• Genetic testing confirming mutations in the DNMT3B gene or other related genes.

Management

Management of ICF syndrome focuses on treating infections and supporting the immune system. This may include:

• Regular administration of intravenous immunoglobulin (IVIG) to boost immune function.
• Prophylactic antibiotics to prevent infections.
• Hematopoietic stem cell transplantation (HSCT) in severe cases.

Prognosis

The prognosis for individuals with ICF syndrome varies depending on the severity of the immunodeficiency and the effectiveness of treatment. Early diagnosis and appropriate management can improve outcomes and quality of life.

Related Pages

• Immunodeficiency
• Chromosome instability
• Genetic disorder
• DNA methylation
• Autosomal recessive