Anxiety disorder as the sole clinical manifestation of a new CADASIL mutation associated with occasional GOM deposits

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary disease of small cerebral vessels. The defective gene involved is NOTCH3. The main clinical manifestations of CADASIL include recurrent transient ischemic attacks, stroke, cognitive impairment, epilepsy, and migraine. Psychiatric symptoms, especially mood disturbances, are also described in CADASIL patients. Aims of the study: Our aim was to understand if CADASIL may be diagnosed in patients with typical white-matter MRI abnormalities but with anxiety disorder as the sole clinical manifestation. Methods: A skin biopsy was collected from a 76-year-old woman who suffered from anxiety. Genetic analysis for NOTCH3 gene mutations and morphological examination by electron microscopy for the detection of deposits of granular osmiophilic material (GOM) in small and medium sized arteries were performed. Results: The patient was diagnosed with CADASIL, leading to discovery of a new heterozygous missense mutation (p.C875R) in NOTCH3 gene. Despite being a common mutation, it has never to our knowledge been described in exon 17 of NOTCH3 gene. Interestingly, it is associated with occasional GOM deposits. Conclusions: Since CADASIL is often underdiagnosed, it is important that psychiatrists consider this potential differential diagnosis in patients with typical white-matter MRI abnormalities.