A novel NOTCH3 mutation and its clinical, neuroimaging and pathological presentation in a Chinese patient with CADASIL: A case report
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Published on: September 8, 2023
Jing Dang1, Shengsuo Lei, Mingwan Xia
1Department of Neurology, Chenzhou No.1 People's Hospital, Chenzhou, Hunan, China.
Insights
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic small vessel disease. Early diagnosis and treatment are vital for improving patient outcomes in CADASIL.
Area of Science:
- Neurology
- Genetics
- Vascular Biology
Background:
- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most prevalent inherited adult cerebral small vessel disease, linked to NOTCH3 gene mutations.
- Disease presentation, including symptom type, onset, and severity, exhibits significant variability among affected individuals.
Observation:
- A case presented with chronic neurological deficits: dysarthria, recurrent limb weakness, and progressive memory decline.
- Neuroimaging demonstrated recurrent lacunar infarcts and extensive white matter lesions.
- Skin biopsy revealed characteristic granular osmiophilic deposits near smooth muscle cells in arterioles, and genetic analysis identified a specific NOTCH3 mutation (c.635G>C[p.(Cys212Ser)]).
Findings:
- The patient was diagnosed with CADASIL based on clinical, imaging, and genetic findings.
- Treatment with antiplatelet agents and physical therapy did not lead to improvement in neurological symptoms.
Implications:
- This case underscores the importance of early and accurate diagnosis of CADASIL for timely intervention.
- Further research into effective therapeutic strategies is crucial for improving the long-term prognosis of CADASIL patients.
Rationale:
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common form of familial cerebral small vessel disease in adults, and is caused by NOTCH3 mutations. However, individual symptom types, onset, and disease severity span a wide range.
Patient Concerns:
Herein, we report a case of chronic neurological symptoms including slurring of speech, recurrent weakness in both limbs and legs, and progressive memory loss. Cranial magnetic resonance imaging revealed recurrent acute lacunar subcortical infarction and extensive white matter hyperintensities. Skin biopsy revealed granular osmiophilic materials close to the cell surface of smooth muscle cells in an arteriolar vessel. The patient's genomic DNA showed a mutation c.635G>C[p.(Cys212Ser)] in exon 4.
Diagnosis:
The patient was finally diagnosed with CADASIL.
Interventions:
The patient was treated with antiplatelet therapy and extremity rehabilitation.
Outcomes:
There was no improvement in speech, extremity function, or memory.
Lessons:
Accurate early diagnosis and appropriate treatment are crucial to improve the prognosis of patients with CADASIL.
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