AGS Article Review

Explore a review of research publications related to Aicardi-Goutieres Syndrome.

By Year: 2024, 2023, 2022, 2021, 2020, 2019, 2018, 2017 and Earlier
By Topic

2024

Characterization of Fine Motor and Visual Motor Skills in Aicardi-Goutières Syndrome

Cusack et al., 2024
Corresponding author: Francesco Gavazzi, gavazzif@chop.edu.
Primary Institution(s): CHOP

Patient Impact: This study found that children with AGS often have trouble with tasks that need precise hand movements, like drawing or picking up small objects, and these issues can affect their daily activities. Understanding these challenges can help families and therapists create better support plans to improve the kids' skills and quality of life.

Research/HCP Impact: The study adds valuable insights into how AGS affects motor skills, helping us understand the condition better and potentially guiding future treatments. It also highlights the importance of early intervention and tailored therapies to support children with AGS more effectively.

The brain microvasculature is a primary mediator of interferon-α neurotoxicity in human cerebral interferonopathies

Viengkhou et al., 2024
Corresponding authors: david.hunt@ed.ac.uk (D.P.J.H.), markus.hofer@sydney.edu.au (M.J.H.)
Primary Institution(s): The University of Sydney, Australia

Patient Impact: The study found that the harmfulness of interferon-alpha can be related to tiny blood vessels in the brain. Understanding how small blood vessels play a role allows for a new treatment target.

Research/HCP Impact: For researchers, this article identified a mediator of interferon-alpha toxicity and offers a target of treatment and prevention of neurotoxicity in AGS. New research must be focused here before development of a new treatment.

Interferon-α receptor antisense oligonucleotides reduce neuroinflammation and neuropathology in a mouse model of cerebral interferonopathy

Viengkhou et al., 2024
Corresponding author: markus.hofer@sydney.edu.au (M.J.H.)
Primary Institution(s): The University of Sydney, Australia

Patient Impact: This study introduces a promising RNA-targeted therapy that effectively halts the progression of AGS in mice. The therapy targets the interferon alpha receptor, which reduces neuroinflammation and neuronal damage while restoring the integrity of the blood-brain barrier. The findings offer hope for potential reversal of AGS's detrimental effects and lay the groundwork for future human trials.

Research/HCP Impact: The study represents a significant advancement in AGS research and treatment. Lead author Dr. Barney Viengkhou and Research Director Patrick Winters of the Aicardi-Goutières Syndrome Advocacy Association express enthusiasm for the therapy's potential to alleviate the burden on affected families. Conducted in collaboration with Ionis Pharmaceuticals and Biogen, the research not only promises to transform the lives of children with AGS but also offers hope for therapy development in other childhood dementias, highlighting the urgent need for innovative treatments and support for affected families.

Interferon signaling gene expression as a diagnostic biomarker for monogenic interferonopathies

Adang et al., 2024
Corresponding author: Adeline Vanderver, vandervera@chop.edu
Primary Institution(s): CHOP

Patient Impact: This study validated and optimized IFN-signaling gene (IGS) expression calculations and demonstrated that IGS expression is a potential diagnostic marker for AGS. For patients, this means a more accurate and quicker diagnosis, leading to earlier treatments.

Research/HCP Impact: This study provides a valuable tool for diagnosing AGS in very early stages. Where genetic testing may take weeks to come back, this method would only take a few days, allowing doctors to begin treating patients earlier. It may also help to guide newborn screening development.

Nonverbal Cognitive Skills in Children With Aicardi Goutières Syndrome

Gavazzi et al., 2024
Corresponding author: Dr. Gavazzi, gavazzif@chop.edu
Primary Institution(s): CHOP

Patient Impact: This study investigated the use of nonverbal skills in children with AGS using the VABS-3 and Leiter-3 tests. Researchers found that motor skills were most impacted in children with AGS compared to communication, daily living, and social skills which were less impacted. For patients, these tests help us better understand strengths and challenges of their child, which can lead to more personalized support and therapies.

Research/HCP Impact: For researchers, this study sheds light on specific cognitive abilities in AGS, helping to refine diagnoses and develop targeted interventions to support these children more effectively.

Systemic complications of Aicardi-Goutières syndrome using real-world data

Adang et al., 2024
Corresponding author: Dr. Laura Adang, adangl@chop.edu
Primary Institution(s): CHOP

Patient Impact: This study highlights that AGS is highly variable and affects multiple systems in the body. This study found that there are often systemic features that present prior to neurological features; characterization of these may aid in early diagnosis and intervention. The paper also characterizes how different systemic features manifest differently based on variables such as genotype and age of onset.

Research/HCP Impact: For researchers, this study provides a helpful characterization of the natural history of AGS and sets the stage for further characterization of symptoms in those who are taking JAK inhibitors. The paper also provides an overview of the systemic complications of AGS, recommendations for monitoring for/managing possible complications, as well as recommendations for routine screening for people with AGS.

2023

JAK Inhibition in Aicardi-Goutières Syndrome: a Monocentric Multidisciplinary Real-World Approach Study

Fremound et al., 2023
Corresponding authors: Yanick J. Crow, yanickcrow@mac.com and Bénédicte Neven, benedicte.neven@aphp.fr
Primary Institution(s): Necker Hospital

Patient Impact: This study looked at using JAK inhibitors to treat Aicardi-Goutières Syndrome. JAK inhibitors might help reduce inflammation and improve symptoms in people with AGS, making life a bit easier for them. However, other treatment may be needed for neurological symptoms, as only patient comfort was improved on a scale that assessed every-day life care.

Research/HCP Impact: For researchers, this study was able to determine the effectiveness of using JAK inhibitors for the neurological symptoms of AGS. Researchers advocate for earlier diagnosis and central nervous system penetration in drug development.

Clinical spectrum and currently available treatment of type I interferonopathy Aicardi-Goutières syndrome

Battisa Dell’Isola et al., 2023
Corresponding author: Giovanni Battista Dell’Isola, giovanni.dellisola@gmail.com
Primary Institution(s): University of Perugia

Patient Impact: This study explored the current available treatments for Aicardi-Goutières Syndrome (AGS). It helps patients by outlining what symptoms to watch for and what treatments might be helpful in managing them.

Research/HCP Impact: For researchers, the study highlights the range of AGS symptoms and evaluates current treatments, providing a clearer picture of how best to approach patients with AGS. This helps in improving our understanding and potentially guiding future research to find even better ways to manage AGS.

Exploration of Gross Motor Function in Aicardi-Goutières Syndrome

Gavazzi et al., 2023
Corresponding author: Francesco Gavazzi, MD, PhD, gavazzif@chop.edu
Primary Institution(s): CHOP

Patient Impact: This study evaluated the Gross Motor Function Measure-88 as a tool for determining motor function in people with AGS. They found that patients with SAMHD1 mutations had the most variability in gross motor function and patients with TREX1 mutations had the least variability. Floor effect was the most prominent gross motor function affected.

Research/HCP Impact: For researchers and healthcare professionals, this research provides a new tool to assess gross motor function in patients with AGS. It also sheds light on genotype-phenotype correlations for gross motor function, which can guide the development of better treatments and therapies.

Aicardi-Goutières Syndrome with Congenital Glaucoma Caused by Novel TREX1 Mutation

Swierczynska et al. 2023
Corresponding author: d201018@365.sum.edu.pl or m.swierczynska93@gmail.com
Primary Institution(s): The Affiliated Suzhou Hospital of Nanjing Medical University,

Patient Impact: This is a case report of a child with a rare mutation in TREX1 that presented with congenital glaucoma. The patient had surgery to stabilize intraocular pressure.

Research/HCP Impact: This study highlights the ocular impairment in a newly identified TREX1 mutation. Healthcare providers should be aware of this, as other people with the same mutation should be referred to ophthalmology for evaluation of glaucoma.

Subacute Partially Reversible Leukoencephalopathy Expands the Aicardi-Goutières Syndrome Phenotype

Peixoto de Barcelos et al., 2023
Corresponding author: fernando.kok@mendelics.com.br
Primary Institution(s): University of São Paulo School of Medicine

Patient Impact: This study found that some people with Aicardi-Goutières Syndrome (AGS) experience subacute developmental regression that can improve clinically over time. Brain imaging also showed improvement over time.

Research/HCP Impact: For researchers, this expands our knowledge of AGS symptoms, and helps in refining the overall picture of AGS and its effects.

Treatment response to Janus kinase inhibitor in a child affected by Aicardi-Goutières syndrome

Galli et al., 2023
Corresponding author: Jessica Galli, jessica.galli@unibs.it
Primary Institution(s): University of Brescia

Patient Impact: This study is a case report of the effectiveness of JAK Inhibitors in a 4 year old with AGS. They found that JAK inhibitors improved cognitive, communicative, and relational skills.

Research/HCP Impact: For researchers, the study provides important data on how JAK inhibitors can be effective for treating AGS.

Tocilizumab reduces the unmanageable inflammatory reaction of a patient with Aicardi-Goutières syndrome type 7 during treatment with ruxolitinib

Wang et al., 2023
Corresponding author: Hongmei Song, songhm1021@126.com
Primary Institution(s): Peking Union Medical College

Patient Impact: This study is a case report of the effectiveness of tocilizumab in a 7 year old with AGS. The patient was being treated with ruxolitinib with steroids and thalidomide since the age of 3, and saw improvement in rash, hematological manifestations, and liver function. When tocilizumab was introduced erythrocyte sedimentation rate, a marker for inflammation, decreased.

Research/HCP Impact: For researchers, this study highlights how combining treatments can be effective for managing AGS. It helps expand our knowledge on treating AGS-related inflammation with tocilizumab.

Case report: Pneumocystis jirovecii pneumonia in a severe case of Aicardi-Goutières syndrome with an IFIH1 gain-of-function mutation mimicking combined immunodeficiency

Zeleznik et al., 2023
Corresponding author: Tadej Avcin, tadej.avcin@kclj.si
Primary Institution(s): University Medical Centre Ljubljana

Patient Impact: This study reported a severe case of Aicardi-Goutières Syndrome (AGS) with an IFIH1 gene mutation that led to a serious lung infection called Pneumocystis jirovecii pneumonia. The patient was treated with JAK inhibitors which reduced IFN activation but did not stop neurological symptoms from progressing.

Research/HCP Impact: For researchers, this study expands the symptoms of AGS in patients with an IFIH1 mutation to include recurrent respiratory infections.

Breaking down the cellular responses to type I interferon neurotoxicity in the brain

Viengkhou et al., 2023
Corresponding author: markus.hofer@sydney.edu.au (M.J.H.)
Primary Institution(s): The University of Sydney, Austrailia

Patient Impact: This study explored how type I interferon affects brain cells and causes damage. For patients, this research helps in understanding how their brain might be impacted by AGS and could lead to better ways to manage or reduce this damage.

Research/HCP Impact: For scientists, it provides detailed insights into the cellular processes behind neurotoxicity in AGS, which can guide the development of new treatments. This deeper understanding could ultimately improve strategies for protecting the brain in AGS and similar conditions.

Juvenile Dermatomyositis and Infantile Cerebral Palsy: Aicardi-Gouteres Syndrome, Type 5, with a Novel Mutation in SAMHD1-A Case Report

Sorokina et al., 2023
Corresponding authors: kost-mikhail@yandex.ru or mikhail.kostik@gmail.com
Primary Institution(s): Saint-Petersburg State Pediatric Medical University

Patient Impact: This study described a unique case of Aicardi-Goutières Syndrome (AGS) type 5 where a patient had juvenile dermatomyositis and family history of infantile cerebral palsy. She was found to have a new mutation in the SAMHD1 gene. The patient was treated with corticosteroids, methotrexate, and tofacitinib and showed improvement.

Research/HCP Impact: For researchers, this case highlights the importance of early diagnosis and treatment in patients with AGS. The researchers recommend raising awareness to neurologists, neonatologists, infectious disease specialists, and pediatricians and using a multidisciplinary approach to treatment.

Efficacy and safety of baricitinib in Japanese patients with autoinflammatory type I interferonopathies (NNS/CANDLE, SAVI, And AGS)

Kanazawa et al., 2023
Corresponding author: Taeko Ishii, ishii_taeko@lilly.com
Primary Institution(s): Hyogo Medical University

Patient Impact: This study evaluated the effectiveness of JAK inhibitors in patients with Nakajo-Nishimura syndrome/chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (NNS/CANDLE), stimulator of interferon genes-associated vasculopathy with onset during infancy (SAVI), and Aicardi-Goutières syndrome (AGS). They found JAK inhibitors to be both effective and safe, showing improvement in daily symptoms such as fever, rash, musculoskeletal pain, headache, and fatigue.

Research/HCP Impact: For researchers, the study offers valuable data on how JAK inhibitors work for these specific conditions, improving our understanding of its benefits and safety. This helps in advancing treatments and provides more evidence on how to effectively handle type I interferonopathies.

Efficacy and safety of thalidomide in children with monogenic autoinflammatory diseases: a single-center, real-world-evidence study

Zhang et al., 2023
Corresponding author: Wei Wang, wangwei.a@163.com and Hongmei Song, songhm1021@hotmail.com
Primary Institution(s): Peking Union Medical College

Patient Impact: This study evaluated the effectiveness of thalidomide in patients with autoinflammatory diseases, including 3 patients with Aicardi-Goutières syndrome (AGS). Treatment showed improvement in fever and rash. Patients were able to decrease glucocorticoids use.

Research/HCP Impact: For researchers, this real-world evidence adds to our knowledge of how thalidomide works in these conditions and can guide future treatment choices. It helps us understand the effectiveness and safety of thalidomide, contributing to better management strategies for these rare diseases.

Clinical Non-Penetrance Associated with Biallelic Mutations in the RNase H2 complex

Crow et al., 2023
Corresponding author: yanickcrow@mac.com
Primary Institution(s): University of Edinburgh

Patient Impact: This article discusses the A177T mutation in RNASEH2B. This mutation has been found in patients with AGS, in patients that have isolated spastic paraparesis, and in asymptomatic patients.

Research/HCP Impact: For researchers, this information adds to our understanding of asymptomatic individuals with a genetic diagnosis of AGS. This study raises questions about the possibility of neonatal screening, what age individuals can be expected to remain symptom free, and why certain individuals remain asymptomatic.

2022

Hematologic abnormalities in Aicardi Goutières Syndrome

Adang et al., 2022
Primary Institution(s): CHOP

Patient Impact: The hematological symptoms of AGS were investigated. Researchers determined that multilineage cytopenias were common, including neutropenia, anemia, and thrombocytopenia.

Research/HCP Impact: For researchers and healthcare professionals, this study supports the recommendation of careful monitoring of hematological symptoms in patients with AGS.

JAK: Not Just Another Kinase

Agashe et al., 2022
Corresponding author: ruchi.agashe@yale.edu.
Primary Institution(s): Yale University

Patient Impact: This paper describes the function of JAK kinases and how they can be used in treatment for specific diseases, including AGS.

Research/HCP Impact: For researchers and healthcare providers, this paper provides in depth information about how JAK kinases function. Knowing more about the mechanism of JAK kinases allows for guided drug development.

Aicardi-Goutières syndrome with SAMHD1 deficiency can be diagnosed by unscheduled DNA synthesis test

Senju et al., 2022
Corresponding author: togi@riem.nagoya-u.ac.jp
Primary Institution(s): Nagasaki University Graduate School of Biomedical Sciences

Patient Impact: This is a case report of an individual who was misdiagnosed with Cockanye syndrome. In this patient, unscheduled DNA synthesis was diminished. They were later found to have SAMHD1 mutations.

Research/HCP Impact: This study shows how unscheduled DNA synthesis may be used as a diagnostic marker for people with SAMHD1 mutations. This may allow for earlier diagnosis and appropriate genetic testing being ordered when trying to determine a diagnosis.

Deep White Matter Cysts in a Patient with Aicardi-Goutières Syndrome and SAMHD1 Variants

Poot, 2022
Corresponding author: martin_poot@hotmail.com

Aicardi-Goutières Syndrome due to a SAMHD1 Mutation Presenting with Deep White Matter Cysts

Oleksy et al., 2022
Corresponding authors: barbara.oleksy@imid.med.pl, mrydzanicz@wum.edu.pl
Primary Institution(s): Institute of Mother and Child, Warsaw

Patient Impact: These studies described a case report of a child with SAMHD1 mutations, atypical presentation, and deep white matter cysts. It highlights the utility of MRI and CT scans in diagnosing people with AGS.

Research/HCP Impact: Because early detection allows for earlier treatment, using MRI and CT scan can help inform a diagnosis while waiting for genetic testing results. It also gives insight into an atypical presentation of AGS.

SARS-CoV-2 mRNA-based vaccines in the Aicardi Goutières Syndrome

Takanohashi et al., 2022
Corresponding author: vandervera@email.chop.edu
Primary Institution(s): CHOP

Patient Impact: This study tested the COVID vaccine on whole blood samples from patients with AGS. They found that there was no increase of interferon signaling. Additionally, patient survey reports suggest that the vaccine has been well tolerated.

Research/HCP Impact: Since vaccination in patients with AGS can be risky, this study provided insights into the clinical outcomes of the COVID vaccine. Additionally, it provides insight into mRNA vaccines in general and how they are tolerated in patients with AGS.

Child Neurology: Aicardi-Goutières Syndrome Presenting as Recurrent Ischemic Stroke

Kuang et al., 2022
Corresponding author: hansletter@fudan.edu.cn
Primary Institution(s): Fudan University

Patient Impact: This study is a case presentation of a patient with TREX1 mutations and ischemic stroke. The patient was treated with JAK inhibitors.and did not have a recurrence of stroke.

Research/HCP Impact: This study highlights a case of AGS where there was ischemic stroke. Therefore, with multisystem involvement and stroke in a young patient, AGS should be considered in the differential diagnosis. It also provides evidence for how the microvascular system may be involved in AGS.

Cutaneous Lesions as a Clue to the Etiology of Extensive Intracranial Calcifications: Aicardi-Goutières Syndrome

Zeng et al., 2022
Corresponding author: wanjinchen75@fjmu.edu.cn
Primary Institution(s): Department of Neurology and Institute of Neurology of First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, China

Patient Impact: This study is a case presentation of a person with an atypical AGS presentation. The individual had a history of spastic gait and bizzare behaviors and was diagnosed with cerebral palsy. He had cutaneous lesions on the hands and intracranial calcifications. At 29 years old, he was found to have a pathogenic variant in ADAR.

Research/HCP Impact: This case presentation suggests that in individuals with intracranial calcifications and cutaneous lesions, AGS should be considered in the differential diagnosis.

Analysis of clinical characteristics of children with Aicardi-Goutieres syndrome in China

Wang et al., 2022
Corresponding authors: rogasansz@163.com, songhm1021@126.com
Primary Institution(s): Peking Union Medical College

Patient Impact: This study describes the clinical characteristics of AGS in Chinese patients. They found that onset before 3 occurred in 82.6%, 100% had neurological symptoms, 60.87% had skin manifestations, 47.62% had microcephaly, 52.38% had microcephaly, 42.11% had liver dysfunction, 46.15% had thyroid dysfunction, 66.67% had positive autoimmune antibodies, and 53.85% had elevated sedimentation rate.

Research/HCP Impact: This study expands the clinical symptoms of patients with AGS.

Case Report: Aicardi-Goutières Syndrome Type 6 and Dyschromatosis Symmetrica Hereditaria With Congenital Heart Disease and Mitral Valve Calcification - Phenotypic Variants Caused by Adenosine Deaminase Acting on the RNA 1 Gene Homozygous Mutations

Liu et al., 2022
Corresponding author: liuliqun@csu.edu.cn
Primary Institution(s): The Second Xiangya Hospital of Central South University

Patient Impact: This study is a case presentation of a patient with ADAR mutations and hyper/hypo pigmented macules on the skin and significant heart findings including patent ductus arteriosus, ventricular septal defect, and mitral valve calcification. These are findings that have not been reported in other patients with AGS.

Research/HCP Impact: This study highlights a case of AGS where there were significant heart findings. It expands the AGS phenotype and shows how referral to cardiology may be appropriate for patients with AGS.

Cerebrospinal fluid neopterin as a biomarker of treatment response to Janus kinase inhibition in Aicardi-Goutières syndrome

Han et al., 2022
Corresponding author: russell.dale@health.nsw.gov.au
Primary Institution(s): The University of Sydney

Patient Impact: This article discusses how JAK inhibitor treatment effectiveness can be monitored by looking at cerebrospinal fluid neopterin levels. Patients have been shown to have decreased neopterin levels after treatment.

Research/HCP Impact: This article provides a way to measure treatment effectiveness so that we are not over or undertreating patients.

Case Report: Generalised Panniculitis as a Post-COVID-19 Presentation in Aicardi-Goutières Syndrome Treated With Ruxolitinib

Pararajasingam et al., 2022
Corresponding author: jollessr@cardiff.ac.uk
Primary Institution(s): Aneurin Bevan University Health Board

Patient Impact: This article describes a case report of an AGS patient post COVID. They had panniculitis and were treated with a JAK inhibitor. After treatment, the patient showed improvement.

Research/HCP Impact: This study describes a unique response following COVID infection and provides an effective treatment option.

Janus Kinase Inhibitors in the Treatment of Type I Interferonopathies: A Case Series From a Single Center in China

Li et al., 2022
Corresponding author: songhm1021@126.com
Primary Institution(s): Peking Union Medical College

Patient Impact: This study investigated the safety of JAK inhibitors in patiens with AGS. They found that patients treated for a mean period of 2.5 years showed decreased cutaneous lesions and fevers, and improved erythrocyte sedimentation rate, catch up growth, and lung function.

Research/HCP Impact: The results of this study suggest that JAK inhibitors are effective treatment options for patients with AGS. However, further research on this topic is needed in larger populations.

2021

Opsoclonus-myoclonus in Aicardi-Goutières syndrome

Alburkaiky et al., 2021
Corresponding author: cynthiaS@adhb.govt.nz
Primary Institution(s): Necker Hospital

Patient Impact: This article discusses children who were diagnosed with AGS and had opsoclonus-myoclonus after developmental regression and irritability. They were treated with JAK inhibitors and had a positive treatment response.

Research/HCP Impact: This study highlights cases of AGS where there was opsoclonus-myoclonus and expands the AGS phenotype. Therefore, in patients with these symptoms and developmental regression, AGS should be considered in the differential diagnosis.

Hepatic Involvement in Aicardi-Goutières Syndrome

Gavazzi et al., 2021
Corresponding author: adangl@email.chop.edu
Primary Institution(s): CHOP

Patient Impact: This paper discusses the liver involvement in patients with AGS. Liver enzymes were elevated in 74.5%. Hepatitis was associated with early onset AGS and microcephaly.

Research/HCP Impact: This paper expands our knowledge about liver involvement in AGS, making providers more aware of the symptoms to look out for.

The epileptology of Aicardi-Goutières syndrome: electro-clinical-radiological findings

De Giorgis et al., 2021
Corresponding author: costanza.varesio@mondino.it
Primary Institution(s): IRCCS Mondino Foundation

Patient Impact: This article describes the association between epilepsy and AGS. Researchers looked at patient brain MRIs and found that 37% had epilepsy, and EEG electrical activity was severely disrupted in 73% of cases. There was also presence of focal slow and fast activity and the presence of IEDs in patients with and without epilepsy.

Research/HCP Impact: This article describes the presence of epilepsy in patients with AGS, making providers more aware of the symptoms to look out for. It suggests the need for neurological monitoring in patients with AGS.

Case Report: Aicardi-Goutières Syndrome Caused by Novel TREX1 Variants

Wu et al., 2021
Corresponding author: yingsc@ahmu.edu.cn
Primary Institution(s): The First Affiliated Hospital of Anhui Medical University

Patient Impact: This paper is a case report of a child with AGS with newly identified TREX1 mutations. She presented with mild rashes, increase in limb muscle tension, and positive cervical correction reflex. Brain MRi showed decreased white matter volume, enlarged ventricles, and a widened sulcus fissure, and abnormal signaling.

Research/HCP Impact: This article describes two new mutations that are associated with AGS, allowing future diagnosis for patients who have the same mutations.

Pons Calcifications and Striatal Necrosis in ADAR1 Aicardi-Goutières Syndrome

Mendes Pinto et al., 2021
Corresponding author: cat.mendes.pinto@gmail.com
Primary Institution(s): Centro Hospitalar Universitario do Porto

Patient Impact: This paper is a case report of a 19 year old male that was diagnosed with AGS. He presented with brainstem calcifications confined to the pons and striatal necrosis.

Research/HCP Impact: This paper discusses the MRI findings of someone with ADAR1-related AGS. The absence of white matter has been previously described and supports a diagnosis of AGS.

Case Report: Aicardi-Goutières Syndrome and Singleton-Merten Syndrome Caused by a Gain-of-Function Mutation in IFIH1

Xiao et al., 2021
Corresponding author: luozhaohui_xy@126.com
Primary Institution(s): Central South University, Changsha, China

Patient Impact: This paper is a case report of a patient who had phenotypes that overlap with both AGS and Singleton-Merten syndrome.

Research/HCP Impact: This is evidence that AGS and SMS could be on the same disease spectrum. It highlights the genetic heterogeneity of these two conditions.

**Case Report: Novel Compound Heterozygous RNASEH2B Mutations Cause Aicardi-Goutières Syndrome**

Garau et al., 2021
Corresponding author: orietta.pansarasa@mondino.it
Primary Institution(s): IRCCS Mondino Foundation

Patient Impact: This study is a case report of a patient that was found to have a new mutation in RNASEH2B. The patient also had lower levels of RNase H2A protein.

Research/HCP Impact: This study describes a new mutation that causes AGS. It also highlights the importance of diagnosing AGS via clinical, genetic, and molecular analysis.

Genetic Testing Contributes to Diagnosis in Cerebral Palsy: Aicardi-Goutières Syndrome as an Example

Beysen et al., 2021
Corresponding author: Marije.Meuwissen@uza.be
Primary Institution(s): Antwerp University Hospital

Patient Impact: This paper discusses 3 cases where patients were clinically diagnosed with cerebral palsy and after genetic testing was pursued, were found to have AGS.

Research/HCP Impact: This study explains cases where AGS is undiagnosed. It emphasizes the need for genetic testing for AGS in patients who are clinically diagnosed with cerebral palsy. It also suggests a link between AGS and CP.

Childhood-Onset Dystonia Attributed to Aicardi-Goutières Syndrome and Responsive to Deep Brain Stimulation

Saraf et al., 2021
Corresponding author: drsyam@sctimst.ac.in
Primary Institution(s): Sree Chitra Tirunal Institute for Medical Sciences and Technology

Patient Impact: This study is a case report about a 20 year old female with a mild clinical and radiological phenotype. She presented with generalized dystonia that improved with deep brain stimulation.

Research/HCP Impact: This study expands the AGS phenotype and gives insight into an atypical presentation of AGS. It also provides a potential effective treatment for AGS patients with dystonia.

**Case Report: The JAK-Inhibitor Ruxolitinib Use in Aicardi-Goutieres Syndrome Due to ADAR1 Mutation**

Cattalini et al., 2021
Corresponding author: marco.cattalini@unibs.it
Primary Institution(s): Azienda Socio Sanitaria Territoriale Spedali Civili di Brescia

Patient Impact: This study is a case report of the effectiveness of JAK inhibitors in patients with ADAR1 mutations. The patient was treated with JAK inhibitors and her affected brother was not. The patient consistently showed lower interferon scores. Additionally, there was slight neurological improvement.

Research/HCP Impact: This paper describes the effectiveness of JAK inhibitors in people with ADAR1 mutations.

Efficacy and Safety of Janus Kinase Inhibitors in Type I Interferon-Mediated Monogenic Autoinflammatory Disorders: A Scoping Review

Gomez-Arias et al., 2021
Corresponding author: juanruanoruiz@mac.com
Primary Institution(s): Maimonides Biomedical Research Institute of Cordoba (IMIBIC)

Patient Impact: This paper is a systematic review of JAK inhibitors. There have been variable responses in patients with CANDLE, SAVI, FCh-L, GOF-STAT1, and AGS. Treatment improved clinical parameters and decreased flares, plasma inflammatory markers, and expression of IFN-stimulated genes. Side effects included upper respiratory infections.

Research/HCP Impact: This review provides insight into all of the research that has been done on JAK inhibitors. It provides insight into the efficacy and safety of this treatment in patients with AGS.

Systemic inflammation and chronic kidney disease in a patient due to the RNASEH2B defect

He et al., 2021
Corresponding author: hetingyan2017@outlook.com; rogasansz@163.com
Primary Institution(s): Shenzhen Children’s Hospital

Patient Impact: This article is a case presentation of a patient with AGS who has neurological manifestations, autoinflammation, and chronic kidney disease. The patient was found to have 3 mutations in the RNASEH2B gene.

Research/HCP Impact: This is only the second known case of AGS with kidney disease. It highlights how AGS can have a variable phenotype and the importance of kidney surveillance in people with AGS.

Type I interferonopathies with novel compound heterozygous TREX1 mutations in two siblings with different symptoms responded to tofacitinib

Zhang et al., 2021
Corresponding author: ypliu@ibms.pumc.edu.cn; wangtaopumch@126.com
Primary Institution(s): Chinese Academy of Medical Sciences and Peking Union Medical College

Patient Impact: This paper is a case report of a family with variants TREX1. One sibling had skin lesions, while the other had severe cutaneous involvement and cerebral palsy. Treatment with JAK inhibitors were effective.

Research/HCP Impact: This study describes a new mutation that causes AGS. It also highlights the variability in clinical presentation in people with AGS and the effectiveness of JAK inhibitors in treating AGS.

2020

Late-Onset Aicardi-Goutieres Syndrome: A Characterization of Presenting Clinical Features

Piccoli et al., 2020
Corresponding author: Laura Adang, adangl@email.chop.edu
Primary Institution(s): CHOP

Patient Impact: This study describes late onset AGS and its clinical course and variability. For patients, it expands our knowledge of the prognosis of a person with late-onset AGS.

Research/HCP Impact: For researchers, it highlights the importance of diagnosis in atypical AGS. Researchers recommend genetic testing when there is inflammation or motor symptoms of an unknown cause in children over one year old.

Treatments in Aicardi-Goutières syndrome

Crow et al., 2020
Corresponding author: yanickcrow@mac.com
Primary Institution(s): University of Edinburgh

Patient Impact: This paper summarizes the implications of therapeutic options for AGS, the utility of treatment, and the challenges of assessing efficacy of treatment.

Research/HCP Impact: For researchers, this paper highlights the first attempts at targeted treatment.

Janus Kinase Inhibition in the Aicardi–Goutières Syndrome

Vanderver et al., 2020
Corresponding author: vandervera@email.chop.edu
Primary Institution(s): CHOP

Patient Impact: This article summarizes the results from a clinical trial that tested JAK inhibitors in patients with AGS. While being treated, 20 patients met new milestones and 12 gained 2-7 new skills.

Research/HCP Impact: For researchers, this study shows how JAK inhibitors can be useful in treating AGS. It also discussed risks associated with treatment and appropriate provider monitoring.

Developmental Outcomes of Aicardi Goutières Syndrome

Adang et al., 2020
Corresponding author: adangl@email.chop.edu
Primary Institution(s): CHOP

Patient Impact: This paper characterized the clinical presentation of AGS by genotype. They found that genotype and environment played a role in disease severity.

Research/HCP Impact: For researchers, this paper provides insight into the genotype-phenotype correlations in AGS. It allows providers to counsel families more appropriately and to better monitor and treat symptoms.

Endocrinopathies in Aicardi Goutières syndrome-A descriptive case series

Worth et al., 2020
Corresponding author: chrisworth88@doctors.org.uk
Primary Institution(s): Royal Manchester Children's Hospital

Patient Impact: This paper describes case reports of patients who have AGS and have hypothyroidism and diabetes.

Research/HCP Impact: For researchers, this paper highlights the importance of monitoring thyroid function and for diabetes in children with AFS. Screening and regular assessment are recommended.

Diagnosis of Aicardi-Goutières Syndrome in Adults: A Case Series

Videira et al., 2020
Corresponding author: pgoncalomv@gmail.com
Primary Institution(s): Centro Hospitalar Universitário do Porto,

Patient Impact: This paper discusses case studies of patients who had mutations in the RNASEH2B gene and were diagnosed with AGS in adulthood. All of the patients were diagnosed after chilblains and basal ganglia calcifications. There was one slightly symptomatic patient and one completed asymptomatic patient.

Research/HCP Impact: For providers, this study highlights how patients with AGS can present differently and be diagnosed at different points in life. It highlights how chilblains and basal ganglia calcifications can be important for adult diagnosis.

Development of a neurologic severity scale for Aicardi Goutières Syndrome

Adang et al., 2020
Corresponding author: adangl@email.chop.edu
Primary Institution(s): CHOP

Patient Impact: This study compared a newly developed scale to AGS severity and composite neurological function scores to determine if it was reliable to use in patients with AGS. Researchers found that the scale correlated with the GMFM-88 tool previously described.

Research/HCP Impact: For researchers and providers, this study developed a scale to assess and monitor neurological function in patients with AGS.

Relapsing-remitting clinical course expands the phenotype of Aicardi-Goutières syndrome

Lambe et al., 2020
Corresponding author: avenkat2@jhmi.edu
Primary Institution(s): Johns Hopkins

Patient Impact: This paper is a case report of a patient who presented with bilateral leg weakness at 12 months old. Her symptoms did not progress until 23 years old when she began to experience spasticity and weakness in her legs and arms. At age 24, the patient was diagnosed with AGS.

Research/HCP Impact: This is an unusual case of AGS and expands the phenotype of the condition. It highlights the variability in presentation of people with AGS and highlights how genetic testing can be useful in determining a diagnosis.

Interstitial Lung Disease and Psoriasis in a Child With Aicardi-Goutières Syndrome

Zheng et al., 2020
Corresponding author: litian-wang@163.com, zhouq2@zju.edu.cn
Primary Institution(s): Guangdong Second Provincial General Hospital

Patient Impact: This paper describes a case report of a patient with AGS who has psoriasis, interstitial lung disease, and pulmonary hypertension. After treatment with corticosteroids, cyclophosphamide, and JAK inhibitors, symptoms improved.

Research/HCP Impact: This study highlights a case of AGS where there was psoriasis and interstitial lung disease and expands the AGS phenotype. Therefore, in patients with AGS, lung disease screening and monitoring should be done.

Novel RNASEH2C mutation in multiple members of a large family: insights into phenotypic spectrum of Aicardi-Goutières Syndrome

Lhamtsho et al., 2020
Corresponding author: vishalsondhi@gmail.com
Primary Institution(s): Armed Forces Medical College

Patient Impact: This paper is a case report of a family with a newly discovered RNASEH2C mutation. It describes the symptoms of patients with AGS and shows that carriers of AGS can have chilblains.

Research/HCP Impact: For researchers, this paper described the phenotype of a family with RNASEH2C mutations, which will aid in earlier diagnosis of AGS. It also provided insight into carrier symptoms of AGS, which should be counseled on.

2019

JAK-inhibitors. New players in the field of immune-mediated diseases, beyond rheumatoid arthritis

Fragoulis et al., 2019
Corresponding author: Iain.McInnes@glasgow.ac.uk
Primary Institution(s): University of Glasgow

Patient Impact: This paper summarizes the clinical data for the use of JAK inhibitors in other autoimmune conditions than rheumatoid arthritis. In patients with AGS, ruxolitinib has been used and there was a good response.

Research/HCP Impact: For providers, this paper provides insight into the function of JAK inhibitors and their efficacy, safety, and use in treating patients with AGS.

Recurrent Encephalopathy with Spinal Cord Involvement: An Atypical Manifestation of Aicardi-Goutières Syndrome

Samanta et al., 2019
Corresponding author: dsamanta@uams.edu
Primary Institution(s): University of Arkansas For Medical Sciences

Patient Impact: This paper is a case report of a patient who had recurrent encephalopathy when sick. The patient had extensive spinal cord swelling and brain signal abnormalities. He also had dyschromatosis symmetrica hereditaria of the skin. The patient was found to have an ADAR mutation.

Research/HCP Impact: For researchers, this is the first documented case of a patient with spinal cord involvement and an ADAR mutation. It also shows the importance of identification of dyschromatosis symmetrica hereditaria for early diagnosis.

Efficacy of Baricitinib in the Treatment of Chilblains Associated With Aicardi-Goutières Syndrome, a Type I Interferonopathy

Meesilpavikkai et al., 2019
Primary Institution(s): Erasmus University Medical Center Rotterdam

Patient Impact: This paper discusses a case report of a patient who started JAK inhibitors at the age of 22. They previously had persistent chillibans on their hands and feet. After 6 weeks, chilblains resolved and there was no recurrence. Additionally, biomarkers in the blood decreased after treatment.

Research/HCP Impact: For researchers, this study provides insight on how JAK inhibitors can be used to treat chilblains in patients with AGS.

2018

Reverse-Transcriptase Inhibitors in the Aicardi–Goutières Syndrome

Rice et al., 2018
Corresponding author: yanickcrow@mac.com
Primary Institution(s): University of Manchester

Patient Impact: This paper discusses reverse transcriptase inhibitor treatment on 11 patients with AGS. Interferon score fell following treatment.

Research/HCP Impact: For researchers and providers, this paper shows the effectiveness of reverse transcriptase inhibitors in treating AGS. However, a larger patient population needs to be studied before implementing treatment.

Aicardi goutières syndrome is associated with pulmonary hypertension

Adang et al., 2018
Corresponding author: adangl@email.chop.edu
Primary Institution(s): CHOP

Patient Impact: Researchers investigated the cardiac function of patients with AGS. They found an that in patients with AGS, there was an increased incidence of pulmonary hypertension.

Research/HCP Impact: This paper expands our knowledge about pulmonary hypertension in AGS, making providers more aware of the symptoms to look out for.

Unusual Association of Aniridia with Aicardi-Goutières Syndrome-Related Congenital Glaucoma in a Tertiary Care Center

Musalem et al., 2018
Corresponding author: hebamusallam91@gmail.com
Primary Institution(s): Alfaisal University

Patient Impact: This paper is a case report of a patient with congenital glaucoma, nystagmus, spherophakia, and aniridia in both eyes. He was found to have a mutation in the IFIH1 gene.

Research/HCP Impact: This paper expands the AGS phenotype to include bilateral aniridia. Monitoring for this should be done in patients with AGS.