HTRA1 -Related Cerebral Small Vessel Disease: A Review of the Literature.
Level 4 - case-series / case-control
Literature review and pooled case-series of published individual case reports
PubMed 32719647 · doi:10.3389/fneur.2020.00545
What was done
The authors reviewed published literature on *HTRA1*-related cerebral small vessel disease (CSVD) to compare clinical, neuroimaging, and genetic features between 46 symptomatic heterozygous *HTRA1* mutation carriers and 28 patients with homozygous *HTRA1* mutations (CARASIL).
What was found
A total of 28 mutations in symptomatic carriers and 22 mutations in CARASIL were identified across 74 patients. Missense mutations in symptomatic carriers clustered more frequently in the linker or loop 3 (L3)/loop D (LD) domains. Age at onset of neurological symptoms was significantly higher in symptomatic carriers than in CARASIL, while extraneurological findings and confluent white matter hyperintensities were significantly more frequent in CARASIL (exact numerical values and p-values not provided in the abstract).
Why it matters
This review differentiates the clinical and genetic profiles of heterozygous *HTRA1*-related CSVD from classic CARASIL, highlighting that heterozygous mutations present as a milder, later-onset phenotype with distinct mutational clustering.
Limits
The analysis is a retrospective literature-based aggregation of individual published cases subject to publication and reporting bias. Exact statistical metrics and values are not reported in the abstract, and the sample size is limited by the rarity of the conditions.
Cited by
- supports CARASIL is a genetic form of small vessel disease caused by HTRA1 mutations that exhibits white matter disease, microbleeds, lacunes, and blood-brain barrier dysfunction.