Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S)
General description
Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is an autosomal dominant systemic small-vessel disease caused by C-terminal frameshift mutations in the TREX1 gene. TREX1 encodes the three prime repair exonuclease 1, which is the most abundant mammalian 3′-5′ DNA exonuclease responsible for degrading cytosolic DNA and maintaining genomic stability.
Clinical manifestations
RVCL-S typically manifests between ages 35 and 50 years. The disease follows a predictable clinical course with progressive visual impairment as the most common presenting symptom, followed by neurological deterioration and systemic manifestations.
Ocular manifestations include progressive bilateral visual loss due to retinal vasculopathy, characterized by retinal hemorrhages, cotton wool spots, intraretinal microvascular abnormalities, and eventual neovascularization leading to visual field defects and potential blindness
Neurological symptoms develop shortly after visual impairment and include focal neurological deficits such as hemiparesis, facial weakness, aphasia, hemianopsia, cognitive impairment, migraine, and psychiatric disturbances such as depression or anxiety.
Systemic manifestations include liver disease typically presenting as microvascular hepatopathy with elevated alkaline phosphatase and gamma-glutamyltransferase, nephropathy manifesting as arterionephrosclerosis and glomerulosclerosis, anemia often associated with microscopic gastrointestinal bleeding, hypertension, and Raynaud's phenomenon.
References
- Hoogeveen, E. S., et al. "Neuroimaging findings in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations." American Journal of Neuroradiology 42.9 (2021): 1604-1609.
- Stam, Anine H., et al. "Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations." Brain 139.11 (2016): 2909-2922.
White matter lesion
T2-hyperintense periventricular frontal lobe white matter lesions are present in almost all the patients, representing the earliest and most consistent imaging finding. The lesions frequently demonstrate nodular enhancement on gadolinium-enhanced T1-weighted images. Central susceptibility artifacts develop within the lesions over time, corresponding to dystrophic calcifications that are visible on CT
Basal ganglia and cerebellum
The basal ganglia, particularly the putamen and caudate nucleus, may demonstrate punctiform enhancing lesions in patients with advanced disease. The thalamus can also be affected, though less commonly than the periventricular white matter regions. Cerebellar involvement becomes more prominent in patients older than 50 years of age, manifesting as punctate enhancing lesions primarily affecting the cerebellar white matter and molecular layer.