Recurrent Cervicocephalic Dissections are Associated with Variants in Connective Tissue Disease Genes (P2.3-060)

Objective: To present four cases of recurrent, spontaneous cervicocephalic artery dissections in which gene variants associated with connective tissue disease were identified. Background: Spontaneous cerebral and cervical artery dissections are a major cause of ischemic stroke in the young. It is hypothesized that genetic variants associated with connective tissue disorder may predispose to an underlying arteriopathy. Design/Methods: Case series Results: CASE 1: A 30-year-old man presented with top-of-the-basilar syndrome secondary to left vertebral artery (VA) dissection and returned a month later with a contralateral VA dissection. An aortopathy genetic panel identified a variant of COL5A2, a gene associated with classic-type Ehlers-Danlos syndrome. CASE 2: A 47-year-old woman with prior left internal carotid artery (ICA) dissection presented with neck pain. CTA demonstrated a dissection of the right ICA. A variant in the COL3A1 gene was discovered. A variant with identical aminoacid alteration is pathogenic for Ehlers-Danlos syndrome, type IV. CASE 3: A 49-year-old woman with prior left ICA dissection presented with pulsatile tinnitus caused by contralateral ICA dissection. A variant in the MYLK gene was identified. Mutations of this gene cause familial thoracic aortic aneurysms and dissections. CASE 4: A 26-year-old woman presented with neck pain. MRA demonstrated a right VA dissection at the V3 level. One year later, she developed vertigo due to a dissection within the right V4 segment. A variant was identified in the FBN2 gene which has been associated with congenital contractural arachnodactyly. Conclusions: The etiology of most spontaneous dissections remains unknown, but a connective tissue disorder is often suspected. As this small case series demonstrates, patients with recurrent dissections may represent a cohort with a higher likelihood of identifying a connective tissue disease gene variant. Further investigation is necessary as the clinical significance of these variants is not well understood but may open an avenue for new treatment options. Disclosure: Dr. Ridha has nothing to disclose. Dr. Mintz has nothing to disclose. Dr. Voetsch has nothing to disclose.