Aicardi-Goutieres syndrome: a Mendelian mimic of congenital infection

Abstract

In 1988, we have drawn attention to the consistent finding of raised levels of interferon-alpha (IFN) in the cerebro-spinal fluid (CSF) and serum of infants affected with a severe genetically determined encephalopathy. These encephalopathies called Aicardi-Goutières syndrome (AGS) are characterized by calcifications of the basal ganglia, white matter demyelination and elevated levels of lymphocytes in the cerebrospinal fluid. These features mimic those of acquired in utero viral infection, so that AGS is sometimes mistaken for the sequelae of congenital infection. This diagnostic distinction has obvious importance, given that AGS is an autosomal recessive disorder whose true nature is often only recognized upon the birth of a second affected child. Recent molecular advances have shown that AGS can be caused by mutations in any one of at least five genes. The relationship between the involved disrupted nuclease pathways and the production of IFN leading to CNS damage in AGS is discussed.