Aicardi-Goutières syndrome panel [7 genes]
Basal ganglia calcification is a non-specific finding that can occur in the context of certain infectious, metabolic, and genetic syndromes. It can simply constitute a benign incidental finding (around 1% of CT scans performed for other reasons in patients over age 60) or a sequela of a connatal infection. However, genetic testing must be considered if clinical symptoms of unknown origin are present, particularly in patients with a positive family history.
Two conditions have been taken into account when developing this panel:
- In children, Aicardi-Goutières syndrome (AGS) is an early-onset encephalopathy presenting with cerebral atrophy, leukodystrophy, and typically basal ganglia calcifications and high interferon levels in CSF. Several related genes have been described (RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, TREX1, ADAR, and IFIH1), which reach a diagnostic yield of 90-95% in cases with suspected AGS (Crow et al., 2015). Since its original description (Aicardi and Goutières, 1984), its phenotypic spectrum has been expanded, which must be taken into account, particularly in late-onset forms.
- In adults in their third to fifth decades of life, idiopathic basal ganglia calcification (Fahr’s disease) should be considered: it is an autosomal dominant condition, usually of familial presentation, characterized by symmetrical calcification of the basal ganglia and other regions of the brain. Its clinical picture can range from asymptomatic stages to a wide spectrum of neuropsychiatric symptoms. The genes known to be involved in the development of this disease thus far are SLC20A2, XPR1, PDGFB, and PDGFRB. More recently, two additional genes with autosomal recessive transmission, PCDH12 and MYORG, have been described.
Priority Genes : Genes where there is sufficient evidence (clinical and functional) to consider them associated with the disease; they are included in the clinical practice guidelines.
Secondary Genes: Genes related to the disease, but with a lower level of evidence or that constitute sporadic cases.
* Candidate Genes: Not enough evidence in humans, but potentially associated with the disease.
- Crow YJ, Chase DS, Lowenstein Schmidt J, Szynkiewicz M, Forte GM, Gornall HL, et al. Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1. Am J Med Genet A. 2015 Feb;167A(2):296-312.