Genetically Confirmed CARASIL: Case Report with Novel HTRA1 Mutation and Literature Review

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is an extremely rare monogenic autosomal disease associated with the HtrA serine protease 1 (HTRA 1) gene mutation. Recently, a few genetically confirmed CARASIL cases with novel HTRA1 mutations have been reported in countries other than Japan.

Here, we report a case of a patient presenting with worsening right hemiplegia and hemiparesthesia. Physical examination revealed that the patient had typical clinical features of CARASIL including thinning hair, cognitive impairment, emotional changes, lumbago, and gait disorder. Brain magnetic resonance imaging showed abnormal diffuse symmetric changes in white matter and hypertensive diffusion-weighted imaging signals in the left centrum ovale and right splenium of the corpus callosum, and susceptibility-weighted imaging showed multiple cerebral microbleeds. Lumbar magnetic resonance imaging showed herniated disks with degenerative changes. A genetic test showed a novel homozygous nucleotide variation of c.847G>T in the HTRA1 gene, thereby resulting in p.Gly283Ter. Thus the patient met the diagnostic criteria for CARASIL. We provide a literature review of genetically confirmed CARASIL cases reported to date.

CARASIL is a rare autosomal recessive disease with an HTRA1 mutation. Familiarity with the early clinical and imaging features of CARASIL combined with a genetic test is key for its early diagnosis.