Case of Aicardi-Goutières syndrome diagnosed in adulthood on whole-genome sequencing.

Background

Aicardi-Goutières syndrome (AGS) is a neurogenetic leukoencephalopathy that typically manifests within the first 6 months of life. Classically, AGS presents with an early encephalopathic episode characterised by feeding difficulties, irritability and psychomotor regression or delay. Cutaneous lesions affecting the extremities and epilepsy are common, with symptoms usually evolving over weeks to months before stabilising. Milder phenotypes have been described, often demonstrating relative preservation of language and cognitive function. Case presentation: Here, we report a case of a 31-year-old woman with compound heterozygous variants in the ADAR gene: (GRCh38) NM_001111.4:c.577C>G p.(Pro193Ala) and (GRCh38) NM_001111.4:c.1111_1112del p.(Ser371Cysfs*3), consistent with AGS. The developmental history revealed normal early motor milestones. At age 3, she developed progressive ataxia and hypotonia. Over time, she exhibited spasticity, dystonia and learning difficulties, along with significant cardiac valvular calcification.

Conclusions

The patient was recently referred for consideration of treatment with baricitinib, a selective JAK1/JAK2 inhibitor. This case underscores the importance of considering AGS in individuals with non-classical presentations, particularly when extracerebral calcification is a notable feature.