Premium
Late diagnosis and atypical brain imaging of Aicardi–Goutières syndrome: are we failing to diagnose Aicardi–Goutières syndrome‐2?
Author(s) -
Svingen Leah,
Goheen Mitchell,
Godfrey Rena,
Wahl Colleen,
Baker Eva H,
Gahl William A,
Malicdan May Christine V,
Toro Camilo
Publication year - 2017
Publication title -
developmental medicine and child neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.658
H-Index - 143
eISSN - 1469-8749
pISSN - 0012-1622
DOI - 10.1111/dmcn.13509
Subject(s) - medicine , spastic quadriplegia , encephalopathy , hyperintensity , pediatrics , neuroscience , psychology , cerebral palsy , magnetic resonance imaging , physical medicine and rehabilitation , radiology
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.