Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome 3

Background and History: 

Several families have been reported with this syndrome, a complex inherited disorder involving the immune system, growth, and facial anomalies.

Clinical Correlations: 

Because of the low number of cases reported, the clinical features are not fully described and there seems to be considerable variation.  Growth during pregnancy is slow and newborns may have a low birth weight.  Developmental delays including physical and psychomotor delays are soon evident.  Most individuals are susceptible to recurrent respiratory and ear infections due to defects of the immune system in which circulating gamma globulins are low.  The midface is flat and the ears are low-set.  The eyelids have a prominent extra fold and the eyes appear farther apart than usual.  Strabismus (crossing of the eyes) is often present and the retina has pigmentary abnormalities.

Other more variable signs include extra digits (fingers and toes), kidney dysfunction, hearing loss, abnormal curvature of the spine, mental retardation, and genital anomalies have also been reported.  One patient died at the age of 26 years.

Genetics: 

This condition results from changes (mutations) in a specific gene.  The disorder requires the presence of two such mutations, one from each parent.  When each clinically normal parent contributes one mutation (a 25% probability for each child) the child receives the required two mutations.

Diagnosis and Prognosis: 

This condition requires a multidisciplinary team for diagnosis and care.  The external appearance is altered as described above but these signs are usually nondiagnostic and further detailed evaluations are required.  There are no specific treatments for this condition but infections need to be treated promptly.  Other treatments are focused on specific defects for individuals, such as hearing loss and learning problems.

Additional Information
Inheritance/Pedigree: 
Autosomal recessive