Late diagnosis and atypical brain imaging of Aicardi–Goutières syndrome: are we failing to diagnose Aicardi–Goutières syndrome‐2?

Aicardi–Goutières syndrome ( AGS ) is a rare disorder with in utero or postnatal onset of encephalopathy and progressive neurological deterioration. The seven genetic subtypes of AGS are associated with abnormal type I interferon‐mediated innate immune response. Most patients with AGS present with progressive microcephaly, spasticity, and cognitive impairment. Some, especially those with type 2 ( AGS 2), manifest milder phenotypes, reduced childhood mortality, and relative preservation of physical and cognitive abilities. In this report, we describe two siblings (sister and brother) diagnosed with AGS 2 in their second decade, who exhibited static encephalopathy since 1 year of age with spastic quadriplegia and anarthria but preserved intellect. Both were homozygous for the common pathogenic RNASEH 2B allele (c.529G>A, p.Ala177Thr). Rather than manifesting calcifications and leukoencephalopathy, both had increased iron signal in the basal ganglia. Our report broadens the clinical and imaging spectrum of AGS 2 and emphasizes the importance of including AGS 2 in the differential diagnosis of idiopathic spastic cerebral palsy. What this paper adds We identified two siblings (sister and brother) with atypical Aicardi–Goutières syndrome type 2 due to RNASEH2B mutation. Manifestations included spastic quadriplegia and anarthria but preserved intellect and increased iron signal in the basal ganglia. RNASEH2B ‐related Aicardi–Goutières syndrome type 2 can have present with a variable phenotype, including idiopathic spastic cerebral palsy.