Immunodeficiency Centromeric Instability and Facial Anomalies Syndrome

Syndrome characterized by immune deficiency associated with recurrent infections and facial dysmorphism.

ICF Syndrome.

Approximately 50 cases have been described.

Autosomal recessive.

The immune defect is variable. Patients tend to have a reduction in at least two immunoglobulin classes. Immunodeficiency has been suggested to be caused by the effects of an acquired viral infection in genetically predisposed individuals. Chromosomal abnormalities are multiple and affect the heterochromatic regions of chromosomes 1, 9, and 16. Chromosome 2 is occasionally affected. Chromosomal abnormalities consist of despiralization, chromosome and chromatid breaks, and pairing and interchanges between homologous and nonhomologous chromosomes. Chromosomal abnormalities are generally found only in peripheral blood lymphocytes. Low numbers of T lymphocytes and natural killer (NK) cells are noted. ICF syndrome is caused by mutations of the DNA methyl-transferase 3B (DNMT3B) gene, which has been mapped to 20q11.2.

Based on the findings of severe immunodeficiency with recurrent infections, associated with a high frequency of pericentromeric decondensations and rearrangements in chromosome 1 and 16 upon karyotype analysis of blood samples. Additional clinical signs include short stature and peculiar facies. Laboratory examinations show reduced serum concentrations of immunoglobulin (Ig) A, IgG, IgE, T lymphocytes, and NK cells, whereas serum levels of IgM are increased. The diagnosis is usually made in infancy.

Patients have short stature, failure to thrive, and suffer from mental retardation. The disease affects the head and neck (hypertelorism, epicanthic folds, low-set ears, flat nasal bridge, micrognathia, macroglossia with protrusion of the tongue), gastrointestinal tract (diarrhea, malabsorption), and immune system (recurrent and prolonged respiratory tract infections, resulting in chronic bronchitis, and bronchiectases; maxillary sinusitis, otitis media, cutaneous infections). Most patients die of infections (pulmonary and/or gastrointestinal) even before they reach adolescence.

Intercurrent infections should be treated. Chest radiograph, lung function tests, and arterial blood gas analysis may be helpful. Evaluate the airway for a potential difficult airway management. Mental retardation may impair cooperation. Sedative and/or anxiolytic premedication and the presence of the primary caregiver during induction of anesthesia may be helpful.

Anesthesia in this condition has not been described. The described features suggest that patients may be prone to upper airway obstruction. Both direct laryngoscopy and tracheal intubation should be expected to be difficult. Alternative airway management techniques (e.g., fiberoptic bronchoscope, [intubating] laryngeal mask) should be available. Maintain spontaneous ventilation until the airway has been secured. A recent respiratory tract infection increases the incidence of perioperative complications (laryngospasm, bronchospasm, atelectases, pneumonia). Attention should be paid to strict aseptic technique for any kind of invasive procedures (intravascular catheters, regional anesthesia) in order to prevent infections. Although not described, use of irradiated blood products in these patients is advised to prevent a graft-versus-host reaction.

Muscle relaxant should be avoided until airway has been secured.