The Rare Syndrome Aicardi–Goutières 4: A Case Report and Literature Review

Abstract

Aicardi–Goutières syndrome (AGS) is a genetically heterogeneous type of interferonopathy resulting from defects in the processing or sensing of nucleic acids. The AGS phenotype encompasses a broad range of neurological and non-neurological findings. It presents with a congenital or subacute onset, manifesting as microcephaly, spasticity, dystonia, seizures, cortical blindness, and psychomotor retardation in the first year of life. The radiological and laboratory findings of AGS are generally accompanied by intracranial calcification, white matter abnormalities, cerebral atrophy, and cerebrospinal fluid lymphocytic pleocytosis. A case diagnosed as AGS type 4 among patients presenting to the Balikesir University Medical Faculty pediatric neurology clinic, Türkiye, between August 1, 2024, and February 1, 2025, and undergoing genetic testing was included in the study. The patient exhibited a coarse facial appearance, a low ear line, scoliosis, contractures in the upper and lower extremities, hyperactive deep tendon reflexes, an equivocal Babinski response, and upper and lower extremity muscle strength of 3/5. The patient was started on levetiracetam at 20 mg/kg in two doses for epilepsy. Whole exome sequencing revealed a homozygous pathogenic variant in RNASEH2A. Parental genetic analyses for the targeted variant were heterozygous. In conclusion, the diagnosis of AGS relies on clinical characteristics and genetic testing. Basic neurological characteristics include developmental delay, dystonia, microcephaly, brain calcification, and leukodystrophy. Although data concerning genotype-phenotype in AGS type 4 have been reported in the literature, these are still limited.