Aicardi-Goutières syndrome specific panel

Aicardi-Goutières syndrome specific panel

[7 genes]

TURNAROUND TIME: 6 WEEKS

ADAR IFIH1 RNASEH2A RNASEH2B
RNASEH2C SAMHD1 TREX1

Basal ganglia calcification is a nonspecific 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), a sequel of a connatal infection. However, genetic study 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 and 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 the symmetrical calcification of 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 involved so far are SLC20A2, XPR1, PDGFB, and PDGFRB.
REFERENCES
  1. 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.

 

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VARIANT CLASSIFICATION
Variant classification and clinical usefulness criteria