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Updated: Jul 4, 2025
Longitudinal In Vivo Imaging of the Cerebrovasculature: Relevance to CNS Diseases
Published on: December 6, 2016
An early diagnosed cerebral small vessel disease in a 12-year-old girl
1Department of Neurology, Neurological Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 100045, China.
Insights
Cerebral small vessel disease (CSVD) can occur in children, as shown by a 12-year-old girl with a COL4A1 gene variant. Early genetic screening is crucial for pediatric CSVD diagnosis and stroke prevention.
Area of Science:
- Neurology
- Genetics
- Pediatrics
Background:
- Cerebral small vessel disease (CSVD) is a primary cause of stroke and dementia, predominantly affecting adults.
- Monogenic forms of CSVD are linked to the COL4A1 gene, presenting diverse clinical and neuroimaging features.
- Pediatric CSVD is rare, making early diagnosis and management challenging.
Observation:
- A 12-year-old girl presented with dizziness, learning difficulties, and concentration issues.
- Brain MRI revealed diffuse periventricular leukoencephalopathy, lacunes, and dilated perivascular spaces, mimicking CSVD.
- No vascular risk factors were identified, and other neurological conditions were excluded.
Findings:
- Trio-whole exome sequencing identified a de novo COL4A1 gene variant (c.2662G>A, p.Gly888Arg).
- The patient was diagnosed with a covert, MRI-defined CSVD.
- This case highlights a rare pediatric presentation of CSVD.
Implications:
- Early diagnosis of pediatric CSVD, even without overt cerebrovascular events, is vital.
- Genetic screening for COL4A1 variants should be considered in children with suggestive neuroimaging findings.
- Preventive measures, such as avoiding excessive physical activity and trauma, are recommended to mitigate future stroke risk.
Abstract:
Cerebral small vessel disease (CSVD) is a leading cause of ischaemic and haemorrhagic stroke and a major contributor to dementia. It occurs mostly in adult patients, rarely in children. COL4A1 is a candidate gene in monogenic CSVD with a wide clinical and neuroimaing spectrum. Here we presented a 12-year-old girl with recurrent dizziness, mild learning difficulties and inability to concentrate, the brain MRI showed diffuse periventricular leukoencephalopathy, lacunes in bilateral centrum semiovale, periventricles and basal ganglia, dilated perivascular spaces in bilateral basal ganglia with brain MRA and MRV were normal, highly mimicked the neuroimaging of CSVD regardless of the young age and no episodes of cerebrovascular events for now. We found no vascular risk factors and excluded other diseases such as primary angitis of central nervous system (PACNS). Then a trio-whole exome sequencing was performed. We found a de novo variant of COL4A1 gene c.2662G>A (p.Gly888Arg). She was finally diagnosed as a MRI-defined covert CSVD case. Though there are no specific treatments, with the very early diagnosis in our patient, excessive physical activity, trauma, anticoagulant therapy should be avoided for possible strokes in her future life. Therefore, genetic screening should be considered in familial cases and also in sporadic cases even in pediatric patients when the brain MRI showed diffuse periventricular leukoencephalopathy, dilated perivascular spaces, as well as microhemorrhage, and deep intracerebral hemorrhages, associated with early onset ischemic strokes or not.
