Late-onset Aicardi Goutieres syndrome: a characterization of
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Aicardi Goutieres Syndrome (AGS) is a genetic interferonopathy characterized by early onset of severe neurologic injury with intracranial calcifications, leukoencephalopathy, and systemic inflammation. Increasingly, a spectrum of neurologic dysfunction and presentation beyond the infantile period is being recognized in AGS. The aim of this study was to characterize late-infantile and juvenile onset AGS.

Researchers conducted a multi-institution, retrospective review of individuals with AGS who presented over 1 year old, including medical history, imaging characteristics and suspected diagnoses at presentation. Thirty-four individuals were identified, all with pathogenic variants in RNASEH2B, SAMHD1, ADAR1, or IFIH1. Most individuals had a history of developmental delay and/or systemic symptoms, such as sterile pyrexias and chilblains, followed by a prodromal period associated with increasing symptoms. This was followed by an abrupt onset of neurologic decline (fulminant phase), with a median onset at 1.33 years (range 1.00-17.68 years).

Most individuals presented with a change in gross motor skills (97.0%), typically with increased tone (78.8%). Leukodystrophy was the most common MRI finding (40.0%). Calcifications were less common (12.9%). This is the first study to characterize presentation of late-infantile and juvenile onset AGS and its phenotypic spectrum. Signs of early systemic dysfunction prior to fulminant disease onset and loss of motor symptoms were common.

Researchers strongly recommend genetic testing when there is concern for sustained inflammation of unknown origins or changes in motor skills in children more than one year of age.