Syndrome characterized by immune deficiency associated
with recurrent infections and facial dysmorphism.
Approximately 50 cases have been described.
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
Muscle relaxant should be avoided
until airway has been secured.
Ehrlich M: The ICF syndrome, a DNA methyltransferase 3B deficiency and
immunodeficiency disease. Clin Immunol...