Aicardi-Goutieres Syndrome (TREX1)
Pathogenic variants in the TREX1 gene cause Aicardi-Goutieres syndrome 1 (AGS1), which is inherited in an autosomal recessive manner. AGS1 is a severe neurological syndrome which typically presents during infancy, with more severe cases presenting neonatally. Common clinical manifestations include severe intellectual disability, physical disability, abnormal neurologic findings, hepatosplenomegaly, thrombocytopenia, severe encephalopathy characterized by extreme irritability, intermittent fevers without infection, loss of skills, slowing of head growth and chilblain skin lesions. Life expectancy is decreased.
Occasionally, rare heterozygous pathogenic variants in TREX1 may cause other related diseases inherited in an autosomal dominant manner.
- Retinal vasculopathy with cerebral leukodystrophy is a neurological disorder with onset in adulthood. Clinical manifestations include central nervous system degeneration, loss of vision, stroke, motor impairment, cognitive decline, micronodular cirrhosis, glomerular dysfunction, and systemic vascular involvement (Raynaud phenomenon). Life expectancy is decreased, as the disorder is progressive and usually leads to death 5-10 years after onset.
- Chilblain lupus is a rare cutaneous form of systemic lupus erthematosus with onset in childhood. Clinical manifestations include painful bluish-red plaques or nodular lesions of the skin in peripheral body parts, cutaneous ulcers, and joint pain. The lesions can be induced and/or worsened by cold temperatures. Life expectancy of the individuals is expected to be normal.
No clear genotype-phenotype correlations have been established.
For information about carrier frequency and residual risk, please see the residual risk table.