Table 1.
Type 1 Interferonopathies. Mutated gene, pattern of inheritance and manifestations. Adapted from Table 1 in Volpi S, Picco P, Caorsi R, Candotti F, Gattorno M. Type I interferonopathies in pediatric rheumatology. Pediatric Rheumatology. Pediatric Rheumatology; 2017 Sep 1;:1–12, under the terms of the Creative Commons Attribution 4.0 International License
| Disease | Gene | Inheritance | Manifestations |
|---|---|---|---|
| Aicardi-Goutière Syndrome (AGS) 1 [21, 22•] | TREX-1 | AR and AD | Progressive encephalopathy, basal ganglia calcifications, lymphocytosis, raised IFN-α in CSF (Classical AGS) |
| AGS2 [22•] | RNASEH2B | AR | Clinical features of AGS |
| AGS3 [22•] | RNASEH2C | Clinical features of AGS | |
| AGS4 [22•] | RNASEH2A | AGS with dysmorphic features | |
| AGS5 [22•] | SAMHD1 | AR | Mild AGS, mouth ulcers, deforming arthropathy, cerebral vasculopathy with early onset stroke |
| AGS6 [22•] | ADAR | AR and AD | Classical AGS, bilateral striatal necrosis |
| AGS7 [22•] | IFIH1 | AD | Classical or mild AGS, though may be asymptomatic |
| Retinal vasculopathy with cerebral leukodystrophy (RVCL) [23] | TREX-1 | AD | Retinopathy and cerebrovascular disease, leukodystrophy, dementia, migraines, glomerulopathy |
| Spondyloenchondrodysplasia (SPENCD) [24] | ACP5 | AR | Spondyloenchondrodysplasia, possible combined immunodeficiency, arthritis, thrombocytopenia, short stature |
| STING associated vasculopathy with onset in infancy (SAVI) [25] | TMEM173 | AD | Cutaneous vasculopathy especially acral involvement, interstitial lung disease, fever, arthralgia |
| USP18 deficiency [26] | USP18 | AR | Cerebral calcification and haemorrhage, hepatomegaly, thrombocytopenia |
| ISG15 deficiency [18••] | ISG15 | AR | Increased susceptibility to mycobacterial infections, basal ganglia calcification, seizures |
| Singleton-Merten Syndrome (SMS) [27, 28] | IFIH1, DDX58 | AD | Cardiovascular sequelae, aortic calcification, dental and skeletal abnormalities, psoriasiform cutaneous lesions |
| Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) [29] | PSMA3, PSMB4, PSMB8, PSMB9, POMP | AD | Panniculitis, lipodystrophy, joint contractures, basal ganglia calcification, fever, arthritis, myositis, dyslipidaemia and metabolic syndrome, aseptic lymphocytic meningitis |
| Trichohepatoenteric syndrome (THES) [30] | SKIV2L | AR | Intractable diarrhoea, woolly hair, intrauterine foetal growth restriction, facial dysmorphism and short stature, immunodeficiency |
| X-linked reticulate pigmentary disorder (XLPDR)[31] | POLA1 | XR | Hyperpigmented skin lesions; GI disease including gastroenteritis, colitis; failure to thrive |
| DNase II deficiency [32] | DNASE2 | AR | Cytopenias, hepatosplenomegaly, fever, non-erosive deforming arthropathy, cutaneous vasculitic lesions, membranoproliferative glomerulonephritis |
| Familial chilblain lupus [33] | TREX1, SAMHD1, TMEM173 | AD | Chilblain lesions, arthralgia, lymphopenia |
ADAR1 adenosine deaminase acting on RNA 1, ACP5 acid phosphastase 5, tartrate resistant, AGS Aicardi-Goutière syndrome, AD autosomal dominant, AR autosomal recessive, CANDLE chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature, CSF cerebrospinal fluid, DDX58 DEAD box protein 58, IFIH1 IFN-induced helicase C domain-containing protein 1, ISG15 interferon-stimulated gene 15, POLA1 DNA polymerase alpha 1, PSMA proteosome subunit alpha type, PSMB proteosome subunit beta type, RNASEH2 ribonuclease H2, RVCL Retinal vasculopathy with cerebral leukodystrophy, SAMHD1 deoxynucleoside triphosphohydrolase SAM domain and HD domain 1, SPENCD spondyloenchondrodysplasia, SAVI STING associated vasculopathy with onset in infancy, PRAAS proteosome-associated autoinflammatory syndrome, SMS Singleton-Merten Syndrome, THES Trichohepatoenteric syndrome, TMEM173 Transmembrane protein 173, TREX1 DNA 3’ – repair exonuclease 1, USP18 ubiquitin-specific peptidase 18, XLPDR X-linked reticulate pigmentary disorder, XR X-linked recessive