Spontaneous coronary artery dissection with leucoencephalopathy associated with thrombospondin Type 1 domain containing 1 gene mutation: a case report

Spontaneous coronary artery dissection (SCAD) is increasingly diagnosed as one of the infrequent causes of acute coronary syndrome. Almost no cause was identified in half of the cases. Here, we report a rare case of spontaneous coronary artery dissection with leucoencephalopathy (SCADLE) associated with a mutation of the thrombospondin Type 1 domain containing 1 (THSD1) gene.

A 36-year-old lady who presented with ischaemic type chest pain for 4 h duration and found to have anterior ST elevation myocardial infarction. She was thrombolysed with tenecteplase and had good resolution. Her coronary angiogram revealed a spontaneous dissection in the left anterior descending artery (LAD) with TIMI 3 flow. Intra-vascular ultrasound study confirmed the LAD spiral dissection and intramural haematoma. She has had recurrent transient ischaemic attacks 5 years and 7 years ago, and there was a significant family history of young stroke. Her magnetic resonance imaging (MRI) brain showed peri-ventricular white matter hyper-intensities and lacunar infarcts suggestive of leucoencephalopathy. An association with cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) and SCAD was suspected, and exome gene sequencing followed by genetic analysis was performed. It identified a variant c.67°C > G (p. Arg224Gly) in the THSD1 gene with normal NOTCH gene.

Thrombospondin Type 1 domain containing 1 gene encodes proteins involving in the extra-cellular matrix (ECM). This THSD1 mutation is inherited as an autosomal dominant fashion and associated with arterial dissections (rare), fibromuscular dysplasia, intra-cranial aneurysm, and subarachnoid haemorrhages. Therefore, SCADLE could be a result of arteriopathy secondary to dysfunction of ECM proteins in cerebral and coronary vasculature resulting in neurological manifestations and MRI features like in CADASIL and SCAD.