Phenotypic Variability in a Family with Aicardi-Goutières Syndrome Due to the Common A177T RNASEH2B Mutation

Aicardi-Goutières syndrome (AGS) is a rare inflammatory encephalopathy mimicking in utero acquired viral infection. Cardinal findings comprise leukodystrophy, basal ganglia calcifications and cerebral atrophy along with cerebrospinal fluid lymphocytosis and elevated interferon-α. In the majority of cases AGS is inherited as an autosomal recessive trait and caused by mutations in six genes including RNASEH2A, RNASEH2B, RNASEH2C, TREX1, SAMHD1 and ADAR1, all of which encode enzymes acting on nucleic acid species. Most patients present with first neurological signs in early infancy and experience severe global developmental delay. Here, we report on the unusual divergent phenotype of two siblings who both carry the most frequent AGS causing p.A177T (c.529G > A) RNASEH2B mutation in the homozygous state. While one sibling showed a typical AGS presentation with early onset and severe statomotor and mental impairment, the older sibling was intellectually completely normal. She was only diagnosed because of mild spasticity of the legs and serological signs of autoimmunity. These findings highlight the phenotypic variability of AGS and suggest that AGS may be underdiagnosed among children with mild cerebral palsy.

Use of pCONUS HPC for the treatment of unruptured wide- necked bifurcation aneurysms: early clinical experience using single antiplatelet therapy

Background In recent years,a growing number of stents and stent-like devices have become available to facilitate the treatment of challenging aneurysms.However,the need for dual antiplatelet therapy can limit their use,especially in ruptured aneurysms.The hydrophilic polymer coating(pHPC,phenox)is a novel glycan-based multilayer polymer that reduces platelet adhesion.This study aims to report our initial experience using the pCONUS HPC device for the treatment of unruptured wide-necked bifurcation aneurysms(WNBA)using acetylsalicylic acid(ASA)as single antiplatelet therapy(SAPT).Methods We retrospectively identified all patients who were treated with the pCONUS HPC for unruptured WNBA in a multi-staged procedure using ASA as SAPT.Records were made of periprocedural complications,clinical outcome and angiographic and clinical follow-up.Results We identified 15 patients with 15 WNBA.The average age was 69 years old(range,41-76).Seven aneurysms were located in the middle cerebral artery,five in the anterior communicating artery,two at the basilar tip and one in the posterior communicating artery.Immediate post-treatment angiography showed five aneurysms with modified Raymond-Roy classification(mRRC)grade Ⅰ and four aneurysms with mRRC grade Ⅱ.There were no haemorrhagic complications.Four patients developed thrombus formation during the second treatment session,all of them completely resolving after administration of glycoprotein Ⅱb/Ⅲa antagonists.Angiographic follow-up data were available for 10 patients and showed adequate occlusion(mRRC Ⅰ or Ⅱ)in eight aneurysms(80%).In-stent stenosis was observed in one patient whereas two patients showed de novo stenosis in one of the efferent branches.Conclusions This early experience on the use of the pCONUS HPC device suggests that it can be useful for treating unruptured WNBA under ASA as SAPT.Further investigation with a randomised treatment registry and larger cohort is needed.