OVERVIEW
Aicardi-Goutieres syndrome is a rare group of inherited disorders with predominantly neurologic and cutaneous involvement. The main clinical features include multiple intracranial calcified foci, cerebral white matter lesions, cerebrospinal fluid chronic lymphocytosis, and frostbite-like skin lesions. The disease is usually inherited in an autosomal recessive manner, but a very small number of autosomal dominant cases also exist. The vast majority of children are born normal with progressive microcephaly and encephalopathy.
Etiology
The disease is mostly inherited in an autosomal recessive manner, with a few cases of autosomal dominant inheritance. Genetic studies show that the genes for the disease are diverse, and seven causative genes have been identified so far, including TREX1, RNASEH2B, RNASEH2C, RNASEH2A, SAMHD1, ADAR1 and IFIH1 genes.
Symptoms
The vast majority of children are born with normal markers, and the disease may strike in the first few days or month of life, manifesting as a severe subacute encephalopathy with seizures, a frostbite-like rash on the skin, and aseptic fever, usually with feeding difficulties, irritability, psychomotor regression, or developmental delays. Some patients present with hepatosplenomegaly and thrombocytopenia in the neonatal period. Symptoms develop over several months (microcephaly and pyramidal fasciculations develop during this period) before stabilizing. Although most children have rapid progression of symptoms within the first year of life, some have a slow progression, with the main symptoms including dystonia, dyskinesia, or cognitive delays.
Examination
1. Cerebrospinal fluid (CSF) examination: shows lymphocytosis and increased alpha-interferon levels.
2. TORCH test: negative.
3. Imaging examination: mainly showing small speckled calcification in the nucleus accumbens, sometimes calcification is also seen in the subcortical white matter. Different degrees of cerebral atrophy are also seen, and signs of cerebral leukoencephalopathy are lacking despite delayed myelination of the white matter.
4. Histopathologic examination: microangiopathy is seen.
5. Corresponding genetic tests are performed.
Diagnosis
1. Onset within 1 year of age, with progressive neurologic lesions.
2. Normal head circumference at birth.
3. Imaging examination showed calcification involving the basal ganglia, sometimes calcification was also seen in the white matter.
4. Cerebrospinal fluid cytosis.
5. TORCH test results are negative.
6. Pathogenic mutations in the corresponding genes are detected.
Differential diagnosis
This disease needs to be differentiated from TORCH syndrome and congenital infections.
Treatment
There is no specific treatment for this disease. Symptoms such as feeding difficulties, delayed psychomotor development, and possible seizures are treated symptomatically.
Prognosis
About 80% of children with severe symptoms die within 10 years of age, while children with milder symptoms live longer.
Prevention
If the causative gene is clearly identified in a preexisting condition, parents should undergo genetic counseling and prenatal molecular diagnosis for a second pregnancy.