A rapidly progressive, familial encephalopathy with calcifications of the basal ganglia, cerebral white matter abnormalities, cerebral atrophy, progressive microcephaly, chronic cerebrospinal fluid (CSF) lymphocytosis, and elevated levels of interferon-α in CSF and serum. This syndrome may progress fast into a vegetative state and early death.
Familial Infantile Encephalopathy with Calcification of Basal Ganglia.
Approximately 400 cases have been described to date, but the incidence is unknown.
Depending on the gene carrying the causative mutation, seven subtypes of AGS can be distinguished.
|Type ||Inheritance ||Frequency (%) ||Gene ||Location |
|AGS 1 ||AD, AR ||22-25 ||TREX1 ||3p21.31 |
|AGS 2 ||AR ||36-40 ||RNASEH2B ||13q14.3 |
|AGS 3 ||AR ||12-14 ||RNASEH2C ||11q13.1 |
|AGS 4 ||AR ||4-5 ||RNASEH2A ||19p13.2 |
|AGS 5 ||AR ||13 ||SAMHD1 ||20q11.23 |
|AGS 6 ||AR ||7 ||ADAR ||1q21.3 |
|AGS 7 ||AD ||3% ||IFIH1 ||2q24 |
The largest survey to date of 374 patients with AGS found that the most common mutations occurred in RNASEH2B. The clinical features and course vary somewhat by genotype. In AGS 1 with mutations in the TREX1-gene the mortality is rather high, whereas in AGS 2 with RNASEH2B mutations the neurological deficiencies are slightly milder and the life expectancy longer. Incomplete penetrance of the same underlying mutations can result in very different neurological and developmental outcomes in different patients, even within affected families.
First described in 1984 by the French pediatric neurologists Jean François Marie Aicardi (1926-2015) and Françoise Goutiéres.
Initially rather unspecific symptoms like irritability, feeding and sleeping difficulties, and unexplained low-grade fevers. Chilblain-like skin lesions on fingers, toes, and ears may appear. The diagnosis is later based on the clinical presentation of early-onset, progressive encephalopathy with psychomotor delay, spasticity, extrapyramidal signs, abnormal eye movements, and microcephaly (becoming obvious in the first year of life). It is associated with chronic CSF lymphocytosis (pleocytosis) and elevated serum- and CSF-levels of interferon-α. The CSF-levels of neopterin and biopterin are elevated and 5-methyltetrahydrofolate is reduced. A CT- or MRI-scan of the brain shows cerebral atrophy (mainly white matter), hydrocephalus, leukoencephalopathy, delayed myelination, cysts in the temporal and frontal lobes and calcifications in the basal ganglia (putamen, globus pallidus, caudate nucleus), the dentate nuclei, thalamus, lobar white matter, and cerebellum. The heterogeneity of the neuroradiologic findings is partly explained by the timing of the disease onset. This medical condition resembles the neurological sequelae of congenital infections, thus positive TORCH (T...