Autosomal dominant ADAR c.3019G>A (p.(G1007R)) variant is an important mimic of hereditary spastic paraplegia and cerebral palsy.

Adenosine Deaminase / genetics Autoimmune Diseases of the Nervous System / diagnosis Cerebral Palsy / diagnosis Child, Preschool Diagnosis, Differential Humans Infant Nervous System Malformations / diagnosis RNA-Binding Proteins / genetics Spastic Paraplegia, Hereditary / diagnosis
ADAR Aicardi-Goutières syndrome Cerebral palsy Hereditary spastic paraplegia Interferonopathy Janus kinase inhibitor Neuroinflammation Spastic diplegia Striatal necrosis

Journal

Brain & development
ISSN: 1872-7131
Titre abrégé: Brain Dev
Pays: Netherlands
ID NLM: 7909235

Informations de publication

Date de publication:
Feb 2022
Historique:
received: 18 07 2021
revised: 18 09 2021
accepted: 04 10 2021
pubmed: 28 10 2021
medline: 3 3 2022
entrez: 27 10 2021
Statut: ppublish

Résumé

The type 1 interferonopathy, Aicardi-Goutières syndrome 6 (AGS6), is classically caused by biallelic ADAR mutations whereas dominant ADAR mutations are associated with dyschromatosis symmetrica hereditaria (DSH). The unique dominant ADAR c.3019G>A variant is associated with neurological manifestations which mimic spastic paraplegia and cerebral palsy (CP). We report three cases of spastic paraplegia or CP diagnosed with AGS6 caused by the ADAR c.3019G>A variant. Two children inherited the variant from an asymptomatic parent, and each child had a different clinical course. The youngest case demonstrated relentless progressive symptoms but responded to immunomodulation using steroids and ruxolitinib. The ADAR c.3019G>A variant has incomplete penetrance and is a likely underrecognized imitator of spastic paraplegia and dystonic CP. A high level of clinical suspicion is required to diagnose this form of AGS, and disease progression may be ameliorated by immunomodulatory treatment with selective Janus kinase inhibitors.

Sections du résumé

BACKGROUND BACKGROUND
The type 1 interferonopathy, Aicardi-Goutières syndrome 6 (AGS6), is classically caused by biallelic ADAR mutations whereas dominant ADAR mutations are associated with dyschromatosis symmetrica hereditaria (DSH). The unique dominant ADAR c.3019G>A variant is associated with neurological manifestations which mimic spastic paraplegia and cerebral palsy (CP).
CASE SUMMARIES METHODS
We report three cases of spastic paraplegia or CP diagnosed with AGS6 caused by the ADAR c.3019G>A variant. Two children inherited the variant from an asymptomatic parent, and each child had a different clinical course. The youngest case demonstrated relentless progressive symptoms but responded to immunomodulation using steroids and ruxolitinib.
CONCLUSION CONCLUSIONS
The ADAR c.3019G>A variant has incomplete penetrance and is a likely underrecognized imitator of spastic paraplegia and dystonic CP. A high level of clinical suspicion is required to diagnose this form of AGS, and disease progression may be ameliorated by immunomodulatory treatment with selective Janus kinase inhibitors.

Identifiants

DOI: 10.1016/j.braindev.2021.10.001 PMID: 34702576
pubmed: 34702576
pii: S0387-7604(21)00185-6
doi: 10.1016/j.braindev.2021.10.001
pii:
doi:

Substances chimiques

RNA-Binding Proteins 0
ADAR protein, human EC 3.5.4.37
Adenosine Deaminase EC 3.5.4.4

Types de publication

Case Reports

Langues

eng

Sous-ensembles de citation

IM

Pagination

153-160

Informations de copyright

Copyright © 2021 The Japanese Society of Child Neurology. All rights reserved.

Auteurs

Hannah F Jones (HF)

Neurology Department, The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, New South Wales, Australia; Starship Hospital, Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, New Zealand.

Marion Stoll (M)

Molecular Medicine Laboratory, Concord Repatriation General Hospital, NSW Health Pathology, Australia.

Gladys Ho (G)

Molecular Genetics Department, The Children's Hospital at Westmead, Australia; Discipline of Child & Adolescent Health, University of Sydney, Sydney, New South Wales 2006, Australia; Discipline of Genetic Medicine, University of Sydney, Sydney, New South Wales 2006, Australia.

Dugald O'Neill (D)

Neurology Department, The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, New South Wales, Australia.

Velda X Han (VX)

Khoo-Teck Puat-National University Children's Medical Institute, National University Health System, Singapore.

Simon Paget (S)

Kids Rehab, The Children's Hospital at Westmead, New South Wales, Australia.

Kirsty Stewart (K)

Kids Rehab, The Children's Hospital at Westmead, New South Wales, Australia.

Jennifer Lewis (J)

Kids Rehab, The Children's Hospital at Westmead, New South Wales, Australia.

Kavitha Kothur (K)

Neurology Department, The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, New South Wales, Australia.

Christopher Troedson (C)

Neurology Department, The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, New South Wales, Australia.

Yanick J Crow (YJ)

MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom; Laboratory of Neurogenetics and Neuroinflammation, Institute Imagine, Université de Paris, Paris, France.

Russell C Dale (RC)

Neurology Department, The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, New South Wales, Australia; Discipline of Child & Adolescent Health, University of Sydney, Sydney, New South Wales 2006, Australia.

Shekeeb S Mohammad (SS)

Neurology Department, The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, New South Wales, Australia; Discipline of Child & Adolescent Health, University of Sydney, Sydney, New South Wales 2006, Australia. Electronic address: shekeeb.mohammad@health.nsw.gov.au.

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Classifications MeSH

questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Aminohydrolases › Nucleoside deaminases › Adenosine deaminase › Autosomal dominant ADAR c.3019G>A (p.(G1007R))...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Maladies auto-immunes du système nerveux › Autosomal dominant ADAR c.3019G>A (p.(G1007R))...
questionsmedicales.fr › Maladies du système nerveux › Maladies du système nerveux central › Encéphalopathies › Paralysie cérébrale › Autosomal dominant ADAR c.3019G>A (p.(G1007R))...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Enfant d'âge préscolaire › Autosomal dominant ADAR c.3019G>A (p.(G1007R))...
questionsmedicales.fr › Diagnostic › Diagnostic différentiel › Autosomal dominant ADAR c.3019G>A (p.(G1007R))...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Autosomal dominant ADAR c.3019G>A (p.(G1007R))...
questionsmedicales.fr › Personnes › Tranches d'âge › Nourrisson › Autosomal dominant ADAR c.3019G>A (p.(G1007R))...
questionsmedicales.fr › Malformations et maladies congénitales, héréditaires et néonatales › Malformations › Malformations du système nerveux › Autosomal dominant ADAR c.3019G>A (p.(G1007R))...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Nucléoprotéines › Protéines de liaison à l'ARN › Autosomal dominant ADAR c.3019G>A (p.(G1007R))...
questionsmedicales.fr › Malformations et maladies congénitales, héréditaires et néonatales › Maladies génétiques congénitales › Maladies neurodégénératives héréditaires › Neuropathie héréditaire motrice et sensitive › Paraplégie spasmodique héréditaire › Autosomal dominant ADAR c.3019G>A (p.(G1007R))...