TREX‐1 related Aicardi‐Goutières syndrome improved by Janus kinase inhibitor

• Published in: American journal of medical genetics. Part A Vol. 194; no. 5; pp. e63510 - n/a
• Main Authors: Ryckmans, Claire, Donge, Mylène, Marchèse, Antonia, Mastouri, Meriem, Thomee, Caroline, Stouffs, Katrien, Lieser, Sandra‐Lucile, Scalais, Emmanuel
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.05.2024; Wiley Subscription Services, Inc
• Subjects: Aicardi‐Goutières syndrome; Atrophy; Autoimmune Diseases of the Nervous System - drug therapy; Autoimmune Diseases of the Nervous System - genetics; Azetidines; Basal ganglia; Basal Ganglia Diseases - diagnosis; Basal Ganglia Diseases - drug therapy; Basal Ganglia Diseases - genetics; Calcinosis - genetics; Cerebrospinal fluid; Etiracetam; Female; Glaucoma; Growth rate; Hearing loss; Humans; Infant; interferonopathy; Janus kinase; Janus kinase inhibitor; Janus Kinase Inhibitors; Kinases; Lymphocytosis; Lymphocytosis - cerebrospinal fluid; Lymphocytosis - genetics; Male; Metabolic disorders; Microencephaly; Nervous System Malformations - drug therapy; Nervous System Malformations - genetics; Pregnancy; Purines; Pyrazoles; Seizures; Substantia alba; Sulfonamides; Topiramate; TREX1 gene; Trihexyphenidyl; Aicardi‐Goutières syndrome; Janus kinase inhibitor; interferonopathy; TREX1 gene
• ISSN: 1552-4825; 1552-4833; 1552-4833
• DOI: 10.1002/ajmg.a.63510

Aicardi‐Goutières syndrome (AGS) is a genetic interferonopathy classically characterized by early onset of severe neurologic injury with basal ganglia calcifications, white matter abnormalities, and progressive cerebral atrophy, along with lymphocytosis and raised interferon alpha (INFα) in the cerebrospinal fluid (CSF). Here, we report a 31/2 year‐old patient born with prenatal onset AGS, first manifesting as intra‐uterine growth retardation. Cranial ultrasonography and cerebral MRI revealed ventriculomegaly and periventricular and basal ganglia calcifications, along with cerebral atrophy. Perinatal infections and known metabolic disorders were excluded. Both CSF lymphocytosis and raised INFα were present. Molecular analysis disclosed two already described compound heterozygous pathogenic variants in TREX1 (c. 309dup, p.(Thr104Hisfs*53) and c. 506G > A, p.(Arg169His)). The evolution was marked by severe global developmental delay with progressive microcephaly. Promptly, the patient developed irritability, quadri‐paretic dyskinetic movements, and subsequently tonic seizures. Sensorineural hearing loss was detected as well as glaucoma. Initially, he was symptomatically treated with trihexyphenidyl followed by levetiracetam and topiramate. At age 22 months, baricitinib (0.4 mg/kg/day) was introduced, leading to normal serum INFα levels. Clinically, dyskinetic movements significantly decreased as well as irritability and sleep disturbance. We confirmed that baricitinib was a useful treatment with no major side effect.