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

Piccoli, Cara; Bronner, Nowa; Gavazzi, Francesco; Dubbs, Holly; Simone, Micaela De; Giorgis, Valentina De; Orcesi, Simona; Fazzi, Elisa; Galli, Jessica; Masnada, Silvia; Tonduti, Davide; Varesio, Costanza; Vanderver, Adeline; Vossough, Arastoo; Adang, Laura

doi:10.1016/j.pediatrneurol.2020.10.012

Cited by 25 publications

(21 citation statements)

References 31 publications

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“…Patients with type I interferonopathies present early in life often within the first week of life; prenatal onset has been reported in patients with AGS; however, late-onset cases presenting at ages 14, 18 and 5.6 years with CANDLE/PRAAS, SAVI and AGS, respectively, have been reported. [4][5][6][7][8][9][10][11] Despite CANDLE/PRAAS, SAVI and AGS having distinct clinical phenotypes of varying disease severity, the individual clinical manifestations of these diseases can overlap, and all are associated with high morbidity and mortality if untreated. 4 12 Recent advances in the genetic description of these disorders permit better characterisation of diseasespecific clinical manifestations, and provide evidence supporting the pathogenic role of type I IFN signalling.…”

Section: Introductionmentioning

confidence: 99%

The 2021 European Alliance of Associations for Rheumatology/American College of Rheumatology points to consider for diagnosis and management of autoinflammatory type I interferonopathies: CANDLE/PRAAS, SAVI and AGS

et al. 2022

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ObjectiveAutoinflammatory type I interferonopathies, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome-associated autoinflammatory syndrome (CANDLE/PRAAS), stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) and Aicardi-Goutières syndrome (AGS) are rare and clinically complex immunodysregulatory diseases. With emerging knowledge of genetic causes and targeted treatments, a Task Force was charged with the development of ‘points to consider’ to improve diagnosis, treatment and long-term monitoring of patients with these rare diseases.MethodsMembers of a Task Force consisting of rheumatologists, neurologists, an immunologist, geneticists, patient advocates and an allied healthcare professional formulated research questions for a systematic literature review. Then, based on literature, Delphi questionnaires and consensus methodology, ‘points to consider’ to guide patient management were developed.ResultsThe Task Force devised consensus and evidence-based guidance of 4 overarching principles and 17 points to consider regarding the diagnosis, treatment and long-term monitoring of patients with the autoinflammatory interferonopathies, CANDLE/PRAAS, SAVI and AGS.ConclusionThese points to consider represent state-of-the-art knowledge to guide diagnostic evaluation, treatment and management of patients with CANDLE/PRAAS, SAVI and AGS and aim to standardise and improve care, quality of life and disease outcomes.

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Section: Introductionmentioning

confidence: 99%

The 2021 European Alliance of Associations for Rheumatology/American College of Rheumatology points to consider for diagnosis and management of autoinflammatory type I interferonopathies: CANDLE/PRAAS, SAVI and AGS

et al. 2022

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“…WMH have been described in most interferonopathies (Online Supplemental Data) and appear to be the most common finding in those with a later disease onset when ICC are less common. 25 Neuropathologic studies in AGS show inhomogeneous demyelination and astrogliosis, which is, again, supportive of a microangiopathy. 22,23 WM involvement is most commonly diffuse or with a frontotemporal predominance, but involvement can also be periventricular or patchy.…”

Section: Wm Abnormalitiesmentioning

confidence: 83%

Spectrum of Neuroradiologic Findings Associated with Monogenic Interferonopathies

Benjamin

Sudhakar

D’Arco

et al. 2021

AJNR Am J Neuroradiol

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The genetic interferonopathies are a heterogeneous group of disorders thought to be caused by the dysregulated expression of interferons and are now commonly considered in the differential diagnosis of children presenting with recurrent or persistent inflammatory phenotypes. With emerging therapeutic options, recognition of these disorders is increasingly important, and neuroimaging plays a vital role. In this article, we discuss the wide spectrum of neuroradiologic features associated with monogenic interferonopathies by reviewing the literature and illustrate these with cases from our institutions. These cases include intracerebral calcifications, white matter T2 hyperintensities, deep WM cysts, cerebral atrophy, large cerebral artery disease, bilateral striatal necrosis, and masslike lesions. A better understanding of the breadth of the neuroimaging phenotypes in conjunction with clinical and laboratory findings will enable earlier diagnosis and direct therapeutic strategies.

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“…AGS is a rare genetic interferonopathy with genetic and clinical heterogeneity, characterized by neurologic dysfunction as the hallmark feature. AGS typically results in early‐onset severe intellectual and physical disability, although late‐onset and milder cases have been reported (Crow, 1993; Crow et al, 2015; Piccoli et al, 2021). Additional characteristic features include abnormal brain imaging findings (basal ganglia calcification, white matter abnormalities, early atrophy, and vasculopathy), hepatosplenomegaly, and thrombocytopenia, a clinical presentation also concerning for several acquired congenital infections (Crow, 1993; Rice et al, 2007).…”

Section: Probandmentioning

confidence: 99%

Aicardi‐Goutières syndrome may present with positive newborn screen for X‐linked adrenoleukodystrophy

Tise

Morales

Lee

et al. 2021

American J of Med Genetics Pt A

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We report three unrelated probands, two male and one female, diagnosed with Aicardi‐Goutières syndrome (AGS) after screening positive on California newborn screening (CA NBS) for X‐linked adrenoleukodystrophy (X‐ALD) due to elevated C26:0 lysophosphatidylcholine (C26:0‐LPC). Follow‐up evaluation was notable for elevated C26:0, C26:1, and C26:0/C22:0 ratio, and normal red blood cell plasmalogens levels in all three probands. Diagnoses were confirmed by molecular sequencing prior to 12 months of age after clinical evaluation was inconsistent with X‐ALD or suggestive of AGS. For at least one proband, the early diagnosis of AGS enabled candidacy for enrollment into a therapeutic clinical trial. This report demonstrates the importance of including AGS on the differential diagnosis for individuals who screen positive for X‐ALD, particularly infants with abnormal neurological features, as this age of onset would be highly unusual for X‐ALD. While AGS is not included on the Recommended Universal Screening Panel, affected individuals can be identified early through state NBS programs so long as providers are aware of a broader differential that includes AGS. This report is timely, as state NBS algorithms for X‐ALD are actively being established, implemented, and refined.

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

Cited by 25 publications

References 31 publications

The 2021 European Alliance of Associations for Rheumatology/American College of Rheumatology points to consider for diagnosis and management of autoinflammatory type I interferonopathies: CANDLE/PRAAS, SAVI and AGS

The 2021 European Alliance of Associations for Rheumatology/American College of Rheumatology points to consider for diagnosis and management of autoinflammatory type I interferonopathies: CANDLE/PRAAS, SAVI and AGS

Spectrum of Neuroradiologic Findings Associated with Monogenic Interferonopathies

Aicardi‐Goutières syndrome may present with positive newborn screen for X‐linked adrenoleukodystrophy

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