Table 2.
Monogenic diseases with immune-mediated involvement of the central nervous system.
| Disease | Gene(s) | Dysregulated Signaling Pathway | Principal Clinical Features | Neurological Involvement |
Inheritance |
|---|---|---|---|---|---|
| AGS [9,10] |
TREX1
RNASEH2 (A, B, C) SAMHD1 ADAR IFIH1 |
Type I IFN | Intermittent fevers, hepatosplenomegaly, chilblains | Progressive cerebral atrophy, leukodystrophy, intracranial calcifications, chronic CSF lymphocytosis, progressive psychomotor retardation, seizures |
AD/AR |
| SAVI [11] |
STING/TMEM173 | Severe skin lesions (face, ears, nose, digits), interstitial lung disease, livedo reticularis, Raynaud phenomenon, recurrent fevers |
Developmental delay, brain infarctions |
AD | |
| DADA2 [12,13] |
CECR1/ADA2 | TNFα | Recurrent fevers, systemic vascular inflammation (skin ulcerations, strokes), Raynaud phenomenon |
Neurologic sequelae of stroke, headaches, ataxia | AR |
| CAPS [14,15] |
CIAS1/NLRP3 | IL-1β | Fever, rash, arthralgia | Chronic meningitis with headaches, deafness and blindness (partial or complete), mental retardation |
AD |
Legend: AGS, Aicardi-Goutières syndrome; IFN, interferon; CSF, cerebrospinal fluid; AD, autosomic dominant; AR, autosomic recessive; SAVI, STING-associated vasculopathy with onset in infancy; DADA2, deficiency of adenosine deaminase 2; TNFα, tumor necrosis factor-α; CAPS, cryopyrin-associated autoinflammatory syndrome; IL-1β, interleukin-1β.