Aicardi-Goutieres syndrome (AGS) is a genetic encephalopathy characterized by the inappropriate induction of a type I interferon-mediated immune response and usually results in severe cognitive and physical morbidities. It is named after Jean Aicardi and Francois Goutières who first described the condition in 1984 [Aicardi J, Goutières F (1984) ] in patients who had presented with early onset encephalopathy, basal ganglia calcification, and persistent lymphocytosis in the cerebrospinal fluid. The condition has subsequently been shown to be both genotypically and clinically heterogenous.
Clinical features
There are two distinct forms of the syndrome:
- Early onset
- severe
- affects about 20 percent of all infants who have AGS
- symptoms present at birth with hepatomegaly, splenomegaly, elevated liver enzymes
- irritability & poor feeding (mimicking congenital viral infection)
However the clinical features can be quite heterogenous. The neurological dysfunction is not always severe and need not even be present at all. Other features originally described including microcephaly, intracranial calcification, white matter changes and CSF lymphocytosis are not always present [].
Genetics
AGS is a genetically heterogeneous disease. Most cases of AGS are inherited in an autosomal recessive manner. However it can also be autosomal dominant with heterozygous mutations in TREX, ADAR, or IFIH1 genes. In some cases AGS-associated mutations show incomplete penetrance with children in the same family with the same mutations showing markedly different neurological and developmental outcomes [Crow YJ et al., 2015]. To date AGS has been associated with mutations of seven different genes.